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Sample records for e16 genomic biomarkers

  1. Genomic Biomarkers for Personalized Medicine: Development and Validation in Clinical Studies

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    Shigeyuki Matsui

    2013-01-01

    Full Text Available The establishment of high-throughput technologies has brought substantial advances to our understanding of the biology of many diseases at the molecular level and increasing expectations on the development of innovative molecularly targeted treatments and molecular biomarkers or diagnostic tests in the context of clinical studies. In this review article, we position the two critical statistical analyses of high-dimensional genomic data, gene screening and prediction, in the framework of development and validation of genomic biomarkers or signatures, through taking into consideration the possible different strategies for developing genomic signatures. A wide variety of biomarker-based clinical trial designs to assess clinical utility of a biomarker or a new treatment with a companion biomarker are also discussed.

  2. Salivary proteomic and genomic biomarkers for primary Sjogren's syndrome

    NARCIS (Netherlands)

    Hu, Shen; Wang, Jianghua; Leong, Sonya; Xie, Yongming; Yu, Tianwei; Zhou, Hui; Henry, Sharon; Vissink, Arjan; Pijpe, Justin; Kallenberg, Cees; Elashoff, David; Loo, Joseph A.; Wong, David T.

    2007-01-01

    Objective. To identify a panel of protein and messenger RNA (mRNA) biomarkers in human whole saliva (WS) that may be used in the detection of primary Sjogren's syndrome (SS). Methods. Mass spectrometry and expression microarray profiling were used to identify candidate protein and mRNA, biomarkers

  3. Salivary proteomic and genomic biomarkers for primary Sjogren's syndrome

    NARCIS (Netherlands)

    Hu, Shen; Wang, Jianghua; Leong, Sonya; Xie, Yongming; Yu, Tianwei; Zhou, Hui; Henry, Sharon; Vissink, Arjan; Pijpe, Justin; Kallenberg, Cees; Elashoff, David; Loo, Joseph A.; Wong, David T.

    Objective. To identify a panel of protein and messenger RNA (mRNA) biomarkers in human whole saliva (WS) that may be used in the detection of primary Sjogren's syndrome (SS). Methods. Mass spectrometry and expression microarray profiling were used to identify candidate protein and mRNA, biomarkers

  4. The Present and Future of Biomarkers in Prostate Cancer: Proteomics, Genomics, and Immunology Advancements

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    Pierre-Olivier Gaudreau

    2016-01-01

    Full Text Available Prostate cancer (PC is the second most common form of cancer in men worldwide. Biomarkers have emerged as essential tools for treatment and assessment since the variability of disease behavior, the cost and diversity of treatments, and the related impairment of quality of life have given rise to a need for a personalized approach. High-throughput technology platforms in proteomics and genomics have accelerated the development of biomarkers. Furthermore, recent successes of several new agents in PC, including immunotherapy, have stimulated the search for predictors of response and resistance and have improved the understanding of the biological mechanisms at work. This review provides an overview of currently established biomarkers in PC, as well as a selection of the most promising biomarkers within these particular fields of development.

  5. Noncoding Genomics in Gastric Cancer and the Gastric Precancerous Cascade: Pathogenesis and Biomarkers

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    Alejandra Sandoval-Bórquez

    2015-01-01

    Full Text Available Gastric cancer is the fifth most common cancer and the third leading cause of cancer-related death, whose patterns vary among geographical regions and ethnicities. It is a multifactorial disease, and its development depends on infection by Helicobacter pylori (H. pylori and Epstein-Barr virus (EBV, host genetic factors, and environmental factors. The heterogeneity of the disease has begun to be unraveled by a comprehensive mutational evaluation of primary tumors. The low-abundance of mutations suggests that other mechanisms participate in the evolution of the disease, such as those found through analyses of noncoding genomics. Noncoding genomics includes single nucleotide polymorphisms (SNPs, regulation of gene expression through DNA methylation of promoter sites, miRNAs, other noncoding RNAs in regulatory regions, and other topics. These processes and molecules ultimately control gene expression. Potential biomarkers are appearing from analyses of noncoding genomics. This review focuses on noncoding genomics and potential biomarkers in the context of gastric cancer and the gastric precancerous cascade.

  6. Data Mining Approaches for Genomic Biomarker Development: Applications Using Drug Screening Data from the Cancer Genome Project and the Cancer Cell Line Encyclopedia.

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    David G Covell

    Full Text Available Developing reliable biomarkers of tumor cell drug sensitivity and resistance can guide hypothesis-driven basic science research and influence pre-therapy clinical decisions. A popular strategy for developing biomarkers uses characterizations of human tumor samples against a range of cancer drug responses that correlate with genomic change; developed largely from the efforts of the Cancer Cell Line Encyclopedia (CCLE and Sanger Cancer Genome Project (CGP. The purpose of this study is to provide an independent analysis of this data that aims to vet existing and add novel perspectives to biomarker discoveries and applications. Existing and alternative data mining and statistical methods will be used to a evaluate drug responses of compounds with similar mechanism of action (MOA, b examine measures of gene expression (GE, copy number (CN and mutation status (MUT biomarkers, combined with gene set enrichment analysis (GSEA, for hypothesizing biological processes important for drug response, c conduct global comparisons of GE, CN and MUT as biomarkers across all drugs screened in the CGP dataset, and d assess the positive predictive power of CGP-derived GE biomarkers as predictors of drug response in CCLE tumor cells. The perspectives derived from individual and global examinations of GEs, MUTs and CNs confirm existing and reveal unique and shared roles for these biomarkers in tumor cell drug sensitivity and resistance. Applications of CGP-derived genomic biomarkers to predict the drug response of CCLE tumor cells finds a highly significant ROC, with a positive predictive power of 0.78. The results of this study expand the available data mining and analysis methods for genomic biomarker development and provide additional support for using biomarkers to guide hypothesis-driven basic science research and pre-therapy clinical decisions.

  7. Metabolomic and Genome-wide Association Studies Reveal Potential Endogenous Biomarkers for OATP1B1.

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    Yee, S W; Giacomini, M M; Hsueh, C-H; Weitz, D; Liang, X; Goswami, S; Kinchen, J M; Coelho, A; Zur, A A; Mertsch, K; Brian, W; Kroetz, D L; Giacomini, K M

    2016-11-01

    Transporter-mediated drug-drug interactions (DDIs) are a major cause of drug toxicities. Using published genome-wide association studies (GWAS) of the human metabolome, we identified 20 metabolites associated with genetic variants in organic anion transporter, OATP1B1 (P acids and fatty acid dicarboxylates were among the metabolites discovered using both GWAS and CSA administration. In vitro studies confirmed tetradecanedioate (TDA) and hexadecanedioate (HDA) were novel substrates of OATP1B1 as well as OAT1 and OAT3. This study highlights the use of multiple datasets for the discovery of endogenous metabolites that represent potential in vivo biomarkers for transporter-mediated DDIs. Future studies are needed to determine whether these metabolites can serve as qualified biomarkers for organic anion transporters. Quantitative relationships between metabolite levels and modulation of transporters should be established. © 2016 American Society for Clinical Pharmacology and Therapeutics.

  8. Schizophrenia genomics and proteomics: are we any closer to biomarker discovery?

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    Kramer Alon

    2009-01-01

    Full Text Available Abstract The field of proteomics has made leaps and bounds in the last 10 years particularly in the fields of oncology and cardiovascular medicine. In comparison, neuroproteomics is still playing catch up mainly due to the relative complexity of neurological disorders. Schizophrenia is one such disorder, believed to be the results of multiple factors both genetic and environmental. Affecting over 2 million people in the US alone, it has become a major clinical and public health concern worldwide. This paper gives an update of schizophrenia biomarker research as reviewed by Lakhan in 2006 and gives us a rundown of the progress made during the last two years. Several studies demonstrate the potential of cerebrospinal fluid as a source of neuro-specific biomarkers. Genetic association studies are making headway in identifying candidate genes for schizophrenia. In addition, metabonomics, bioinformatics, and neuroimaging techniques are aiming to complete the picture by filling in knowledge gaps. International cooperation in the form of genomics and protein databases and brain banks is facilitating research efforts. While none of the recent developments described here in qualifies as biomarker discovery, many are likely to be stepping stones towards that goal.

  9. Peripheral blood gene expression as a novel genomic biomarker in complicated sarcoidosis.

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    Tong Zhou

    Full Text Available Sarcoidosis, a systemic granulomatous syndrome invariably affecting the lung, typically spontaneously remits but in ~20% of cases progresses with severe lung dysfunction or cardiac and neurologic involvement (complicated sarcoidosis. Unfortunately, current biomarkers fail to distinguish patients with remitting (uncomplicated sarcoidosis from other fibrotic lung disorders, and fail to identify individuals at risk for complicated sarcoidosis. We utilized genome-wide peripheral blood gene expression analysis to identify a 20-gene sarcoidosis biomarker signature distinguishing sarcoidosis (n = 39 from healthy controls (n = 35, 86% classification accuracy and which served as a molecular signature for complicated sarcoidosis (n = 17. As aberrancies in T cell receptor (TCR signaling, JAK-STAT (JS signaling, and cytokine-cytokine receptor (CCR signaling are implicated in sarcoidosis pathogenesis, a 31-gene signature comprised of T cell signaling pathway genes associated with sarcoidosis (TCR/JS/CCR was compared to the unbiased 20-gene biomarker signature but proved inferior in prediction accuracy in distinguishing complicated from uncomplicated sarcoidosis. Additional validation strategies included significant association of single nucleotide polymorphisms (SNPs in signature genes with sarcoidosis susceptibility and severity (unbiased signature genes - CX3CR1, FKBP1A, NOG, RBM12B, SENS3, TSHZ2; T cell/JAK-STAT pathway genes such as AKT3, CBLB, DLG1, IFNG, IL2RA, IL7R, ITK, JUN, MALT1, NFATC2, PLCG1, SPRED1. In summary, this validated peripheral blood molecular gene signature appears to be a valuable biomarker in identifying cases with sarcoidoisis and predicting risk for complicated sarcoidosis.

  10. Altered metabolomic-genomic signature: A potential noninvasive biomarker of epilepsy.

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    Wu, Helen C; Dachet, Fabien; Ghoddoussi, Farhad; Bagla, Shruti; Fuerst, Darren; Stanley, Jeffrey A; Galloway, Matthew P; Loeb, Jeffrey A

    2017-09-01

    This study aimed to identify noninvasive biomarkers of human epilepsy that can reliably detect and localize epileptic brain regions. Having noninvasive biomarkers would greatly enhance patient diagnosis, patient monitoring, and novel therapy development. At the present time, only surgically invasive, direct brain recordings are capable of detecting these regions with precision, which severely limits the pace and scope of both clinical management and research progress in epilepsy. We compared high versus low or nonspiking regions in nine medically intractable epilepsy surgery patients by performing integrated metabolomic-genomic-histological analyses of electrically mapped human cortical regions using high-resolution magic angle spinning proton magnetic resonance spectroscopy, cDNA microarrays, and histological analysis. We found a highly consistent and predictive metabolite logistic regression model with reduced lactate and increased creatine plus phosphocreatine and choline, suggestive of a chronically altered metabolic state in epileptic brain regions. Linking gene expression, cellular, and histological differences to these key metabolites using a hierarchical clustering approach predicted altered metabolic vascular coupling in the affected regions. Consistently, these predictions were validated histologically, showing both neovascularization and newly discovered, millimeter-sized microlesions. Using a systems biology approach on electrically mapped human cortex provides new evidence for spatially segregated, metabolic derangements in both neurovascular and synaptic architecture in human epileptic brain regions that could be a noninvasively detectable biomarker of epilepsy. These findings both highlight the immense power of a systems biology approach and identify a potentially important role that magnetic resonance spectroscopy can play in the research and clinical management of epilepsy. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  11. Predictive Power Estimation Algorithm (PPEA--a new algorithm to reduce overfitting for genomic biomarker discovery.

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    Jiangang Liu

    Full Text Available Toxicogenomics promises to aid in predicting adverse effects, understanding the mechanisms of drug action or toxicity, and uncovering unexpected or secondary pharmacology. However, modeling adverse effects using high dimensional and high noise genomic data is prone to over-fitting. Models constructed from such data sets often consist of a large number of genes with no obvious functional relevance to the biological effect the model intends to predict that can make it challenging to interpret the modeling results. To address these issues, we developed a novel algorithm, Predictive Power Estimation Algorithm (PPEA, which estimates the predictive power of each individual transcript through an iterative two-way bootstrapping procedure. By repeatedly enforcing that the sample number is larger than the transcript number, in each iteration of modeling and testing, PPEA reduces the potential risk of overfitting. We show with three different cases studies that: (1 PPEA can quickly derive a reliable rank order of predictive power of individual transcripts in a relatively small number of iterations, (2 the top ranked transcripts tend to be functionally related to the phenotype they are intended to predict, (3 using only the most predictive top ranked transcripts greatly facilitates development of multiplex assay such as qRT-PCR as a biomarker, and (4 more importantly, we were able to demonstrate that a small number of genes identified from the top-ranked transcripts are highly predictive of phenotype as their expression changes distinguished adverse from nonadverse effects of compounds in completely independent tests. Thus, we believe that the PPEA model effectively addresses the over-fitting problem and can be used to facilitate genomic biomarker discovery for predictive toxicology and drug responses.

  12. Convergent functional genomics of anxiety disorders: translational identification of genes, biomarkers, pathways and mechanisms.

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    Le-Niculescu, H; Balaraman, Y; Patel, S D; Ayalew, M; Gupta, J; Kuczenski, R; Shekhar, A; Schork, N; Geyer, M A; Niculescu, A B

    2011-05-24

    Anxiety disorders are prevalent and disabling yet understudied from a genetic standpoint, compared with other major psychiatric disorders such as bipolar disorder and schizophrenia. The fact that they are more common, diverse and perceived as embedded in normal life may explain this relative oversight. In addition, as for other psychiatric disorders, there are technical challenges related to the identification and validation of candidate genes and peripheral biomarkers. Human studies, particularly genetic ones, are susceptible to the issue of being underpowered, because of genetic heterogeneity, the effect of variable environmental exposure on gene expression, and difficulty of accrual of large, well phenotyped cohorts. Animal model gene expression studies, in a genetically homogeneous and experimentally tractable setting, can avoid artifacts and provide sensitivity of detection. Subsequent translational integration of the animal model datasets with human genetic and gene expression datasets can ensure cross-validatory power and specificity for illness. We have used a pharmacogenomic mouse model (involving treatments with an anxiogenic drug--yohimbine, and an anti-anxiety drug--diazepam) as a discovery engine for identification of anxiety candidate genes as well as potential blood biomarkers. Gene expression changes in key brain regions for anxiety (prefrontal cortex, amygdala and hippocampus) and blood were analyzed using a convergent functional genomics (CFG) approach, which integrates our new data with published human and animal model data, as a translational strategy of cross-matching and prioritizing findings. Our work identifies top candidate genes (such as FOS, GABBR1, NR4A2, DRD1, ADORA2A, QKI, RGS2, PTGDS, HSPA1B, DYNLL2, CCKBR and DBP), brain-blood biomarkers (such as FOS, QKI and HSPA1B), pathways (such as cAMP signaling) and mechanisms for anxiety disorders--notably signal transduction and reactivity to environment, with a prominent role for the

  13. Genomic biomarkers of prenatal intrauterine inflammation in umbilical cord tissue predict later life neurological outcomes.

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    Sloane K Tilley

    Full Text Available Preterm birth is a major risk factor for neurodevelopmental delays and disorders. This study aimed to identify genomic biomarkers of intrauterine inflammation in umbilical cord tissue in preterm neonates that predict cognitive impairment at 10 years of age.Genome-wide messenger RNA (mRNA levels from umbilical cord tissue were obtained from 43 neonates born before 28 weeks of gestation. Genes that were differentially expressed across four indicators of intrauterine inflammation were identified and their functions examined. Exact logistic regression was used to test whether expression levels in umbilical cord tissue predicted neurocognitive function at 10 years of age.Placental indicators of inflammation were associated with changes in the mRNA expression of 445 genes in umbilical cord tissue. Transcripts with decreased expression showed significant enrichment for biological signaling processes related to neuronal development and growth. The altered expression of six genes was found to predict neurocognitive impairment when children were 10 years old These genes include two that encode for proteins involved in neuronal development.Prenatal intrauterine inflammation is associated with altered gene expression in umbilical cord tissue. A set of six of the differentially expressed genes predict cognitive impairment later in life, suggesting that the fetal environment is associated with significant adverse effects on neurodevelopment that persist into later childhood.

  14. Cadmium-induced genomic instability in Arabidopsis: Molecular toxicological biomarkers for early diagnosis of cadmium stress.

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    Wang, Hetong; He, Lei; Song, Jie; Cui, Weina; Zhang, Yanzhao; Jia, Chunyun; Francis, Dennis; Rogers, Hilary J; Sun, Lizong; Tai, Peidong; Hui, Xiujuan; Yang, Yuesuo; Liu, Wan

    2016-05-01

    Microsatellite instability (MSI) analysis, random-amplified polymorphic DNA (RAPD), and methylation-sensitive arbitrarily primed PCR (MSAP-PCR) are methods to evaluate the toxicity of environmental pollutants in stress-treated plants and human cancer cells. Here, we evaluate these techniques to screen for genetic and epigenetic alterations of Arabidopsis plantlets exposed to 0-5.0 mg L(-1) cadmium (Cd) for 15 d. There was a substantial increase in RAPD polymorphism of 24.5, and in genomic methylation polymorphism of 30.5-34.5 at CpG and of 14.5-20 at CHG sites under Cd stress of 5.0 mg L(-1) by RAPD and of 0.25-5.0 mg L(-1) by MSAP-PCR, respectively. However, only a tiny increase of 1.5 loci by RAPD occurred under Cd stress of 4.0 mg L(-1), and an additional high dose (8.0 mg L(-1)) resulted in one repeat by MSI analysis. MSAP-PCR detected the most significant epigenetic modifications in plantlets exposed to Cd stress, and the patterns of hypermethylation and polymorphisms were consistent with inverted U-shaped dose responses. The presence of genomic methylation polymorphism in Cd-treated seedlings, prior to the onset of RAPD polymorphism, MSI and obvious growth effects, suggests that these altered DNA methylation loci are the most sensitive biomarkers for early diagnosis and risk assessment of genotoxic effects of Cd pollution in ecotoxicology. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Characterization of neurophysiologic and neurocognitive biomarkers for use in genomic and clinical outcome studies of schizophrenia.

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    Gregory A Light

    Full Text Available Endophenotypes are quantitative, laboratory-based measures representing intermediate links in the pathways between genetic variation and the clinical expression of a disorder. Ideal endophenotypes exhibit deficits in patients, are stable over time and across shifts in psychopathology, and are suitable for repeat testing. Unfortunately, many leading candidate endophenotypes in schizophrenia have not been fully characterized simultaneously in large cohorts of patients and controls across these properties. The objectives of this study were to characterize the extent to which widely-used neurophysiological and neurocognitive endophenotypes are: 1 associated with schizophrenia, 2 stable over time, independent of state-related changes, and 3 free of potential practice/maturation or differential attrition effects in schizophrenia patients (SZ and nonpsychiatric comparison subjects (NCS. Stability of clinical and functional measures was also assessed.Participants (SZ n = 341; NCS n = 205 completed a battery of neurophysiological (MMN, P3a, P50 and N100 indices, PPI, startle habituation, antisaccade, neurocognitive (WRAT-3 Reading, LNS-forward, LNS-reorder, WCST-64, CVLT-II. In addition, patients were rated on clinical symptom severity as well as functional capacity and status measures (GAF, UPSA, SOF. 223 subjects (SZ n = 163; NCS n = 58 returned for retesting after 1 year.Most neurophysiological and neurocognitive measures exhibited medium-to-large deficits in schizophrenia, moderate-to-substantial stability across the retest interval, and were independent of fluctuations in clinical status. Clinical symptoms and functional measures also exhibited substantial stability. A Longitudinal Endophenotype Ranking System (LERS was created to rank neurophysiological and neurocognitive biomarkers according to their effect sizes across endophenotype criteria.The majority of neurophysiological and neurocognitive measures exhibited deficits in

  16. Characterization of neurophysiologic and neurocognitive biomarkers for use in genomic and clinical outcome studies of schizophrenia.

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    Light, Gregory A; Swerdlow, Neal R; Rissling, Anthony J; Radant, Allen; Sugar, Catherine A; Sprock, Joyce; Pela, Marlena; Geyer, Mark A; Braff, David L

    2012-01-01

    Endophenotypes are quantitative, laboratory-based measures representing intermediate links in the pathways between genetic variation and the clinical expression of a disorder. Ideal endophenotypes exhibit deficits in patients, are stable over time and across shifts in psychopathology, and are suitable for repeat testing. Unfortunately, many leading candidate endophenotypes in schizophrenia have not been fully characterized simultaneously in large cohorts of patients and controls across these properties. The objectives of this study were to characterize the extent to which widely-used neurophysiological and neurocognitive endophenotypes are: 1) associated with schizophrenia, 2) stable over time, independent of state-related changes, and 3) free of potential practice/maturation or differential attrition effects in schizophrenia patients (SZ) and nonpsychiatric comparison subjects (NCS). Stability of clinical and functional measures was also assessed. Participants (SZ n = 341; NCS n = 205) completed a battery of neurophysiological (MMN, P3a, P50 and N100 indices, PPI, startle habituation, antisaccade), neurocognitive (WRAT-3 Reading, LNS-forward, LNS-reorder, WCST-64, CVLT-II). In addition, patients were rated on clinical symptom severity as well as functional capacity and status measures (GAF, UPSA, SOF). 223 subjects (SZ n = 163; NCS n = 58) returned for retesting after 1 year. Most neurophysiological and neurocognitive measures exhibited medium-to-large deficits in schizophrenia, moderate-to-substantial stability across the retest interval, and were independent of fluctuations in clinical status. Clinical symptoms and functional measures also exhibited substantial stability. A Longitudinal Endophenotype Ranking System (LERS) was created to rank neurophysiological and neurocognitive biomarkers according to their effect sizes across endophenotype criteria. The majority of neurophysiological and neurocognitive measures exhibited deficits in patients

  17. Predictive biomarker discovery through the parallel integration of clinical trial and functional genomics datasets

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    Swanton, C.; Larkin, J.M.; Gerlinger, M.

    2010-01-01

    -cancer agents. The consortium focuses on the identification of reliable predictive biomarkers to approved agents with anti-angiogenic activity for which no reliable predictive biomarkers exist: sunitinib, a multi-targeted tyrosine kinase inhibitor and everolimus, a mammalian target of rapamycin (mTOR) pathway...

  18. atBioNet– an integrated network analysis tool for genomics and biomarker discovery

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    Ding Yijun

    2012-07-01

    Full Text Available Abstract Background Large amounts of mammalian protein-protein interaction (PPI data have been generated and are available for public use. From a systems biology perspective, Proteins/genes interactions encode the key mechanisms distinguishing disease and health, and such mechanisms can be uncovered through network analysis. An effective network analysis tool should integrate different content-specific PPI databases into a comprehensive network format with a user-friendly platform to identify key functional modules/pathways and the underlying mechanisms of disease and toxicity. Results atBioNet integrates seven publicly available PPI databases into a network-specific knowledge base. Knowledge expansion is achieved by expanding a user supplied proteins/genes list with interactions from its integrated PPI network. The statistically significant functional modules are determined by applying a fast network-clustering algorithm (SCAN: a Structural Clustering Algorithm for Networks. The functional modules can be visualized either separately or together in the context of the whole network. Integration of pathway information enables enrichment analysis and assessment of the biological function of modules. Three case studies are presented using publicly available disease gene signatures as a basis to discover new biomarkers for acute leukemia, systemic lupus erythematosus, and breast cancer. The results demonstrated that atBioNet can not only identify functional modules and pathways related to the studied diseases, but this information can also be used to hypothesize novel biomarkers for future analysis. Conclusion atBioNet is a free web-based network analysis tool that provides a systematic insight into proteins/genes interactions through examining significant functional modules. The identified functional modules are useful for determining underlying mechanisms of disease and biomarker discovery. It can be accessed at: http

  19. atBioNet--an integrated network analysis tool for genomics and biomarker discovery.

    Science.gov (United States)

    Ding, Yijun; Chen, Minjun; Liu, Zhichao; Ding, Don; Ye, Yanbin; Zhang, Min; Kelly, Reagan; Guo, Li; Su, Zhenqiang; Harris, Stephen C; Qian, Feng; Ge, Weigong; Fang, Hong; Xu, Xiaowei; Tong, Weida

    2012-07-20

    Large amounts of mammalian protein-protein interaction (PPI) data have been generated and are available for public use. From a systems biology perspective, Proteins/genes interactions encode the key mechanisms distinguishing disease and health, and such mechanisms can be uncovered through network analysis. An effective network analysis tool should integrate different content-specific PPI databases into a comprehensive network format with a user-friendly platform to identify key functional modules/pathways and the underlying mechanisms of disease and toxicity. atBioNet integrates seven publicly available PPI databases into a network-specific knowledge base. Knowledge expansion is achieved by expanding a user supplied proteins/genes list with interactions from its integrated PPI network. The statistically significant functional modules are determined by applying a fast network-clustering algorithm (SCAN: a Structural Clustering Algorithm for Networks). The functional modules can be visualized either separately or together in the context of the whole network. Integration of pathway information enables enrichment analysis and assessment of the biological function of modules. Three case studies are presented using publicly available disease gene signatures as a basis to discover new biomarkers for acute leukemia, systemic lupus erythematosus, and breast cancer. The results demonstrated that atBioNet can not only identify functional modules and pathways related to the studied diseases, but this information can also be used to hypothesize novel biomarkers for future analysis. atBioNet is a free web-based network analysis tool that provides a systematic insight into proteins/genes interactions through examining significant functional modules. The identified functional modules are useful for determining underlying mechanisms of disease and biomarker discovery. It can be accessed at: http://www.fda.gov/ScienceResearch/BioinformaticsTools/ucm285284.htm.

  20. Integrated analysis of epigenomic and genomic changes by DNA methylation dependent mechanisms provides potential novel biomarkers for prostate cancer.

    Science.gov (United States)

    White-Al Habeeb, Nicole M A; Ho, Linh T; Olkhov-Mitsel, Ekaterina; Kron, Ken; Pethe, Vaijayanti; Lehman, Melanie; Jovanovic, Lidija; Fleshner, Neil; van der Kwast, Theodorus; Nelson, Colleen C; Bapat, Bharati

    2014-09-15

    Epigenetic silencing mediated by CpG methylation is a common feature of many cancers. Characterizing aberrant DNA methylation changes associated with tumor progression may identify potential prognostic markers for prostate cancer (PCa). We treated two PCa cell lines, 22Rv1 and DU-145 with the demethylating agent 5-Aza 2'-deoxycitidine (DAC) and global methylation status was analyzed by performing methylation-sensitive restriction enzyme based differential methylation hybridization strategy followed by genome-wide CpG methylation array profiling. In addition, we examined gene expression changes using a custom microarray. Gene Set Enrichment Analysis (GSEA) identified the most significantly dysregulated pathways. In addition, we assessed methylation status of candidate genes that showed reduced CpG methylation and increased gene expression after DAC treatment, in Gleason score (GS) 8 vs. GS6 patients using three independent cohorts of patients; the publically available The Cancer Genome Atlas (TCGA) dataset, and two separate patient cohorts. Our analysis, by integrating methylation and gene expression in PCa cell lines, combined with patient tumor data, identified novel potential biomarkers for PCa patients. These markers may help elucidate the pathogenesis of PCa and represent potential prognostic markers for PCa patients.

  1. Targeted genomic biomarkers for diagnosis and therapy: from basic research to clinical perspective

    International Nuclear Information System (INIS)

    Thakur, Mathew L.

    2014-01-01

    In 2010, more than 30,000 men succumbed to prostate cancer (PC) and more than 240,000 new PC cases were identified in the USA. Digital rectal examination, MRI, and a blood test for prostate specific antigen (PSA) determination play a significant role in detecting advanced PC. However, they are not considered reliable tools for early warning of PC, to detect recurrent cancer or to determine metastatic status of the disease. Unreliable diagnosis results in undertreatment or overtreatment of patients with minimal benefit, enormous morbidity, incontinence, and/or impotence. Histology remains the mainstay of PC confirmation. However, out of >750,000 biopsies performed each year in the USA, >65% show benign pathology, causing patient morbidity and costing hundreds of millions of healthcare dollars. Biological fluids, including urine, represent a promising source of biomarkers for detection and prediction of PC prognosis. Because urine is available non-invasively and readily, numerous studies targeting DNA, RNA, protein and metabolite based biomarkers have been performed. However, none have yet reached the clinic. Even FDA approved PCA3 test has low sensitivity and limitations in predicting aggressive PC

  2. 76 FR 49773 - International Conference on Harmonisation; Guidance on E16 Biomarkers Related to Drug or...

    Science.gov (United States)

    2011-08-11

    ... sponsors are the European Commission; the European Federation of Pharmaceutical Industries Associations... Pharmaceutical Research and Manufacturers of America. The ICH Secretariat, which coordinates the preparation of..., many important initiatives have been undertaken by regulatory authorities and industry associations to...

  3. Biomarker-based classification of bacterial and fungal whole-blood infections in a genome-wide expression study

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    Andreas eDix

    2015-03-01

    Full Text Available Sepsis is a clinical syndrome that can be caused by bacteria or fungi. Early knowledge on the nature of the causative agent is a prerequisite for targeted anti-microbial therapy. Besides currently used detection methods like blood culture and PCR-based assays, the analysis of the transcriptional response of the host to infecting organisms holds great promise. In this study, we aim to examine the transcriptional footprint of infections caused by the bacterial pathogens Staphylococcus aureus and Escherichia coli and the fungal pathogens Candida albicans and Aspergillus fumigatus in a human whole-blood model. Moreover, we use the expression information to build a random forest classifier to classify if a sample contains a bacterial, fungal, or mock-infection. After normalizing the transcription intensities using stably expressed reference genes, we filtered the gene set for biomarkers of bacterial or fungal blood infections. This selection is based on differential expression and an additional gene relevance measure. In this way, we identified 38 biomarker genes, including IL6, SOCS3, and IRG1 which were already associated to sepsis by other studies. Using these genes, we trained the classifier and assessed its performance. It yielded a 96% accuracy (sensitivities >93%, specificities >97% for a 10-fold stratified cross-validation and a 92% accuracy (sensitivities and specificities >83% for an additional test dataset comprising Cryptococcus neoformans infections. Furthermore, the classifier is robust to Gaussian noise, indicating correct class predictions on datasets of new species. In conclusion, this genome-wide approach demonstrates an effective feature selection process in combination with the construction of a well-performing classification model. Further analyses of genes with pathogen-dependent expression patterns can provide insights into the systemic host responses, which may lead to new anti-microbial therapeutic advances.

  4. Implementing an online tool for genome-wide validation of survival-associated biomarkers in ovarian-cancer using microarray data from 1287 patients

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    Győrffy, Balázs; Lánczky, András; Szállási, Zoltán

    2012-01-01

    was set up using gene expression data and survival information of 1287 ovarian cancer patients downloaded from Gene Expression Omnibus and The Cancer Genome Atlas (Affymetrix HG-U133A, HG-U133A 2.0, and HG-U133 Plus 2.0 microarrays). After quality control and normalization, only probes present on all......). A Kaplan–Meier survival plot was generated and significance was computed. The tool can be accessed online at www.kmplot.com/ovar. We used this integrative data analysis tool to validate the prognostic power of 37 biomarkers identified in the literature. Of these, CA125 (MUC16; P=3.7x10–5, hazard ratio (HR...... biomarker validation platform that mines all available microarray data to assess the prognostic power of 22 277 genes in 1287 ovarian cancer patients. We specifically used this tool to evaluate the effect of 37 previously published biomarkers on ovarian cancer prognosis....

  5. Potential candidate genomic biomarkers of drug induced vascular injury in the rat

    International Nuclear Information System (INIS)

    Dalmas, Deidre A.; Scicchitano, Marshall S.; Mullins, David; Hughes-Earle, Angela; Tatsuoka, Kay; Magid-Slav, Michal; Frazier, Kendall S.; Thomas, Heath C.

    2011-01-01

    Drug-induced vascular injury is frequently observed in rats but the relevance and translation to humans present a hurdle for drug development. Numerous structurally diverse pharmacologic agents have been shown to induce mesenteric arterial medial necrosis in rats, but no consistent biomarkers have been identified. To address this need, a novel strategy was developed in rats to identify genes associated with the development of drug-induced mesenteric arterial medial necrosis. Separate groups (n = 6/group) of male rats were given 28 different toxicants (30 different treatments) for 1 or 4 days with each toxicant given at 3 different doses (low, mid and high) plus corresponding vehicle (912 total rats). Mesentery was collected, frozen and endothelial and vascular smooth muscle cells were microdissected from each artery. RNA was isolated, amplified and Affymetrix GeneChip® analysis was performed on selectively enriched samples and a novel panel of genes representing those which showed a dose responsive pattern for all treatments in which mesenteric arterial medial necrosis was histologically observed, was developed and verified in individual endothelial cell- and vascular smooth muscle cell-enriched samples. Data were confirmed in samples containing mesentery using quantitative real-time RT-PCR (TaqMan™) gene expression profiling. In addition, the performance of the panel was also confirmed using similarly collected samples obtained from a timecourse study in rats given a well established vascular toxicant (Fenoldopam). Although further validation is still required, a novel gene panel has been developed that represents a strategic opportunity that can potentially be used to help predict the occurrence of drug-induced mesenteric arterial medial necrosis in rats at an early stage in drug development. -- Highlights: ► A gene panel was developed to help predict rat drug-induced mesenteric MAN. ► A gene panel was identified following treatment of rats with 28

  6. Mapping of genomic EGFRvIII deletions in glioblastoma: insight into rearrangement mechanisms and biomarker development.

    Science.gov (United States)

    Koga, Tomoyuki; Li, Bin; Figueroa, Javier M; Ren, Bing; Chen, Clark C; Carter, Bob S; Furnari, Frank B

    2018-04-12

    Epidermal growth factor receptor (EGFR) variant III (vIII) is the most common oncogenic rearrangement in glioblastoma (GBM) generated by deletion of exons two to seven of EGFR. The proximal breakpoints occur in variable positions within the 123-kb intron one, presenting significant challenges in terms of PCR-based mapping. Molecular mechanisms underlying these deletions remain unclear. We determined the presence of EGFRvIII and its breakpoints for 29 GBM samples using quantitative polymerase chain reaction (qPCR), arrayed PCR mapping, Sanger sequencing, and whole genome sequencing (WGS). Patient-specific breakpoint PCR was performed on tumors, plasma and cerebrospinal fluid (CSF) samples. The breakpoint sequences and single nucleotide polymorphisms (SNPs) were analyzed to elucidate the underlying biogenic mechanism. PCR mapping and WGS independently unveiled eight EGFRvIII breakpoints in six tumors. Patient-specific primers yielded EGFRvIII PCR amplicons in matched tumors, and in cell-free DNA (cfDNA) from a CSF sample, but not in cfDNA or extracellular-vesicle DNA from plasma. The breakpoint analysis revealed nucleotide insertions in four, an insertion of a region outside of EGFR locus in one, microhomologies in three, as well as a duplication or an inversion accompanied by microhomologies in two, suggestive of distinct DNA repair mechanisms. In the GBM samples that harbored distinct breakpoints, the SNP compositions of EGFRvIII and amplified non-vIII EGFR were identical, suggesting that these rearrangements arose from amplified non-vIII EGFR. Our approach efficiently "fingerprints" each sample's EGFRvIII breakpoints. Breakpoint sequence analyses suggest that independent breakpoints arose from precursor amplified non-vIII EGFR through different DNA repair mechanisms.

  7. NCC-AUC: an AUC optimization method to identify multi-biomarker panel for cancer prognosis from genomic and clinical data.

    Science.gov (United States)

    Zou, Meng; Liu, Zhaoqi; Zhang, Xiang-Sun; Wang, Yong

    2015-10-15

    In prognosis and survival studies, an important goal is to identify multi-biomarker panels with predictive power using molecular characteristics or clinical observations. Such analysis is often challenged by censored, small-sample-size, but high-dimensional genomic profiles or clinical data. Therefore, sophisticated models and algorithms are in pressing need. In this study, we propose a novel Area Under Curve (AUC) optimization method for multi-biomarker panel identification named Nearest Centroid Classifier for AUC optimization (NCC-AUC). Our method is motived by the connection between AUC score for classification accuracy evaluation and Harrell's concordance index in survival analysis. This connection allows us to convert the survival time regression problem to a binary classification problem. Then an optimization model is formulated to directly maximize AUC and meanwhile minimize the number of selected features to construct a predictor in the nearest centroid classifier framework. NCC-AUC shows its great performance by validating both in genomic data of breast cancer and clinical data of stage IB Non-Small-Cell Lung Cancer (NSCLC). For the genomic data, NCC-AUC outperforms Support Vector Machine (SVM) and Support Vector Machine-based Recursive Feature Elimination (SVM-RFE) in classification accuracy. It tends to select a multi-biomarker panel with low average redundancy and enriched biological meanings. Also NCC-AUC is more significant in separation of low and high risk cohorts than widely used Cox model (Cox proportional-hazards regression model) and L1-Cox model (L1 penalized in Cox model). These performance gains of NCC-AUC are quite robust across 5 subtypes of breast cancer. Further in an independent clinical data, NCC-AUC outperforms SVM and SVM-RFE in predictive accuracy and is consistently better than Cox model and L1-Cox model in grouping patients into high and low risk categories. In summary, NCC-AUC provides a rigorous optimization framework to

  8. Identification of genomic biomarkers for concurrent diagnosis of drug-induced renal tubular injury using a large-scale toxicogenomics database

    International Nuclear Information System (INIS)

    Kondo, Chiaki; Minowa, Yohsuke; Uehara, Takeki; Okuno, Yasushi; Nakatsu, Noriyuki; Ono, Atsushi; Maruyama, Toshiyuki; Kato, Ikuo; Yamate, Jyoji; Yamada, Hiroshi; Ohno, Yasuo; Urushidani, Tetsuro

    2009-01-01

    Drug-induced renal tubular injury is one of the major concerns in preclinical safety evaluations. Toxicogenomics is becoming a generally accepted approach for identifying chemicals with potential safety problems. In the present study, we analyzed 33 nephrotoxicants and 8 non-nephrotoxic hepatotoxicants to elucidate time- and dose-dependent global gene expression changes associated with proximal tubular toxicity. The compounds were administered orally or intravenously once daily to male Sprague-Dawley rats. The animals were exposed to four different doses of the compounds, and kidney tissues were collected on days 4, 8, 15, and 29. Gene expression profiles were generated from kidney RNA by using Affymetrix GeneChips and analyzed in conjunction with the histopathological changes. We used the filter-type gene selection algorithm based on t-statistics conjugated with the SVM classifier, and achieved a sensitivity of 90% with a selectivity of 90%. Then, 92 genes were extracted as the genomic biomarker candidates that were used to construct the classifier. The gene list contains well-known biomarkers, such as Kidney injury molecule 1, Ceruloplasmin, Clusterin, Tissue inhibitor of metallopeptidase 1, and also novel biomarker candidates. Most of the genes involved in tissue remodeling, the immune/inflammatory response, cell adhesion/proliferation/migration, and metabolism were predominantly up-regulated. Down-regulated genes participated in cell adhesion/proliferation/migration, membrane transport, and signal transduction. Our classifier has better prediction accuracy than any of the well-known biomarkers. Therefore, the toxicogenomics approach would be useful for concurrent diagnosis of renal tubular injury.

  9. Network Biomarkers of Bladder Cancer Based on a Genome-Wide Genetic and Epigenetic Network Derived from Next-Generation Sequencing Data.

    Science.gov (United States)

    Li, Cheng-Wei; Chen, Bor-Sen

    2016-01-01

    Epigenetic and microRNA (miRNA) regulation are associated with carcinogenesis and the development of cancer. By using the available omics data, including those from next-generation sequencing (NGS), genome-wide methylation profiling, candidate integrated genetic and epigenetic network (IGEN) analysis, and drug response genome-wide microarray analysis, we constructed an IGEN system based on three coupling regression models that characterize protein-protein interaction networks (PPINs), gene regulatory networks (GRNs), miRNA regulatory networks (MRNs), and epigenetic regulatory networks (ERNs). By applying system identification method and principal genome-wide network projection (PGNP) to IGEN analysis, we identified the core network biomarkers to investigate bladder carcinogenic mechanisms and design multiple drug combinations for treating bladder cancer with minimal side-effects. The progression of DNA repair and cell proliferation in stage 1 bladder cancer ultimately results not only in the derepression of miR-200a and miR-200b but also in the regulation of the TNF pathway to metastasis-related genes or proteins, cell proliferation, and DNA repair in stage 4 bladder cancer. We designed a multiple drug combination comprising gefitinib, estradiol, yohimbine, and fulvestrant for treating stage 1 bladder cancer with minimal side-effects, and another multiple drug combination comprising gefitinib, estradiol, chlorpromazine, and LY294002 for treating stage 4 bladder cancer with minimal side-effects.

  10. Genomes

    National Research Council Canada - National Science Library

    Brown, T. A. (Terence A.)

    2002-01-01

    ... of genome expression and replication processes, and transcriptomics and proteomics. This text is richly illustrated with clear, easy-to-follow, full color diagrams, which are downloadable from the book's website...

  11. Genome-wide association study of a nicotine metabolism biomarker in African American smokers: impact of chromosome 19 genetic influences.

    Science.gov (United States)

    Chenoweth, Meghan J; Ware, Jennifer J; Zhu, Andy Z X; Cole, Christopher B; Cox, Lisa Sanderson; Nollen, Nikki; Ahluwalia, Jasjit S; Benowitz, Neal L; Schnoll, Robert A; Hawk, Larry W; Cinciripini, Paul M; George, Tony P; Lerman, Caryn; Knight, Joanne; Tyndale, Rachel F

    2018-03-01

    The activity of CYP2A6, the major nicotine-inactivating enzyme, is measurable in smokers using the nicotine metabolite ratio (NMR; 3'hydroxycotinine/cotinine). Due to its role in nicotine clearance, the NMR is associated with smoking behaviours and response to pharmacotherapies. The NMR is highly heritable (~80%), and on average lower in African Americans (AA) versus whites. We previously identified several reduce and loss-of-function CYP2A6 variants common in individuals of African descent. Our current aim was to identify novel genetic influences on the NMR in AA smokers using genome-wide approaches. Genome-wide association study (GWAS). Multiple sites within Canada and the United States. AA smokers from two clinical trials: Pharmacogenetics of Nicotine Addiction Treatment (PNAT)-2 (NCT01314001; n = 504) and Kick-it-at-Swope (KIS)-3 (NCT00666978; n = 450). Genome-wide SNP genotyping, the NMR (phenotype) and population substructure and NMR covariates. Meta-analysis revealed three independent chromosome 19 signals (rs12459249, rs111645190 and rs185430475) associated with the NMR. The top overall hit, rs12459249 (P = 1.47e-39; beta = 0.59 per C (versus T) allele, SE = 0.045), located ~9.5 kb 3' of CYP2A6, remained genome-wide significant after controlling for the common (~10% in AA) non-functional CYP2A6*17 allele. In contrast, rs111645190 and rs185430475 were not genome-wide significant when controlling for CYP2A6*17. In total, 96 signals associated with the NMR were identified; many were not found in prior NMR GWASs in individuals of European descent. The top hits were also associated with the NMR in a third cohort of AA (KIS2; n = 480). None of the hits were in UGT or OCT2 genes. Three independent chromosome 19 signals account for ~20% of the variability in the nicotine metabolite ratio in African American smokers. The hits identified may contribute to inter-ethnic variability in nicotine metabolism, smoking behaviours and tobacco-related disease risk

  12. Single-Nucleotide Variations in Cardiac Arrhythmias: Prospects for Genomics and Proteomics Based Biomarker Discovery and Diagnostics

    Directory of Open Access Journals (Sweden)

    Ayman Abunimer

    2014-03-01

    Full Text Available Cardiovascular diseases are a large contributor to causes of early death in developed countries. Some of these conditions, such as sudden cardiac death and atrial fibrillation, stem from arrhythmias—a spectrum of conditions with abnormal electrical activity in the heart. Genome-wide association studies can identify single nucleotide variations (SNVs that may predispose individuals to developing acquired forms of arrhythmias. Through manual curation of published genome-wide association studies, we have collected a comprehensive list of 75 SNVs associated with cardiac arrhythmias. Ten of the SNVs result in amino acid changes and can be used in proteomic-based detection methods. In an effort to identify additional non-synonymous mutations that affect the proteome, we analyzed the post-translational modification S-nitrosylation, which is known to affect cardiac arrhythmias. We identified loss of seven known S-nitrosylation sites due to non-synonymous single nucleotide variations (nsSNVs. For predicted nitrosylation sites we found 1429 proteins where the sites are modified due to nsSNV. Analysis of the predicted S-nitrosylation dataset for over- or under-representation (compared to the complete human proteome of pathways and functional elements shows significant statistical over-representation of the blood coagulation pathway. Gene Ontology (GO analysis displays statistically over-represented terms related to muscle contraction, receptor activity, motor activity, cystoskeleton components, and microtubule activity. Through the genomic and proteomic context of SNVs and S-nitrosylation sites presented in this study, researchers can look for variation that can predispose individuals to cardiac arrhythmias. Such attempts to elucidate mechanisms of arrhythmia thereby add yet another useful parameter in predicting susceptibility for cardiac diseases.

  13. Institutional Responsibility and the Flawed Genomic Biomarkers at Duke University: A Missed Opportunity for Transparency and Accountability.

    Science.gov (United States)

    DeMets, David L; Fleming, Thomas R; Geller, Gail; Ransohoff, David F

    2017-08-01

    When there have been substantial failures by institutional leadership in their oversight responsibility to protect research integrity, the public should demand that these be recognized and addressed by the institution itself, or the funding bodies. This commentary discusses a case of research failures in developing genomic predictors for cancer risk assessment and treatment at a leading university. In its review of this case, the Office of Research Integrity, an agency within the US Department of Health and Human Services, focused their report entirely on one individual faculty member and made no comment on the institution's responsibility and its failure to provide adequate oversight and investigation. These actions missed an important opportunity to emphasize the institution's critical responsibilities in oversight of research integrity and the importance of institutional transparency and accountability.

  14. A genomic biomarker signature can predict skin sensitizers using a cell-based in vitro alternative to animal tests

    Directory of Open Access Journals (Sweden)

    Albrekt Ann-Sofie

    2011-08-01

    Full Text Available Abstract Background Allergic contact dermatitis is an inflammatory skin disease that affects a significant proportion of the population. This disease is caused by an adverse immune response towards chemical haptens, and leads to a substantial economic burden for society. Current test of sensitizing chemicals rely on animal experimentation. New legislations on the registration and use of chemicals within pharmaceutical and cosmetic industries have stimulated significant research efforts to develop alternative, human cell-based assays for the prediction of sensitization. The aim is to replace animal experiments with in vitro tests displaying a higher predictive power. Results We have developed a novel cell-based assay for the prediction of sensitizing chemicals. By analyzing the transcriptome of the human cell line MUTZ-3 after 24 h stimulation, using 20 different sensitizing chemicals, 20 non-sensitizing chemicals and vehicle controls, we have identified a biomarker signature of 200 genes with potent discriminatory ability. Using a Support Vector Machine for supervised classification, the prediction performance of the assay revealed an area under the ROC curve of 0.98. In addition, categorizing the chemicals according to the LLNA assay, this gene signature could also predict sensitizing potency. The identified markers are involved in biological pathways with immunological relevant functions, which can shed light on the process of human sensitization. Conclusions A gene signature predicting sensitization, using a human cell line in vitro, has been identified. This simple and robust cell-based assay has the potential to completely replace or drastically reduce the utilization of test systems based on experimental animals. Being based on human biology, the assay is proposed to be more accurate for predicting sensitization in humans, than the traditional animal-based tests.

  15. A genomic biomarker signature can predict skin sensitizers using a cell-based in vitro alternative to animal tests

    Science.gov (United States)

    2011-01-01

    Background Allergic contact dermatitis is an inflammatory skin disease that affects a significant proportion of the population. This disease is caused by an adverse immune response towards chemical haptens, and leads to a substantial economic burden for society. Current test of sensitizing chemicals rely on animal experimentation. New legislations on the registration and use of chemicals within pharmaceutical and cosmetic industries have stimulated significant research efforts to develop alternative, human cell-based assays for the prediction of sensitization. The aim is to replace animal experiments with in vitro tests displaying a higher predictive power. Results We have developed a novel cell-based assay for the prediction of sensitizing chemicals. By analyzing the transcriptome of the human cell line MUTZ-3 after 24 h stimulation, using 20 different sensitizing chemicals, 20 non-sensitizing chemicals and vehicle controls, we have identified a biomarker signature of 200 genes with potent discriminatory ability. Using a Support Vector Machine for supervised classification, the prediction performance of the assay revealed an area under the ROC curve of 0.98. In addition, categorizing the chemicals according to the LLNA assay, this gene signature could also predict sensitizing potency. The identified markers are involved in biological pathways with immunological relevant functions, which can shed light on the process of human sensitization. Conclusions A gene signature predicting sensitization, using a human cell line in vitro, has been identified. This simple and robust cell-based assay has the potential to completely replace or drastically reduce the utilization of test systems based on experimental animals. Being based on human biology, the assay is proposed to be more accurate for predicting sensitization in humans, than the traditional animal-based tests. PMID:21824406

  16. Chemogenomics: a discipline at the crossroad of high throughput technologies, biomarker research, combinatorial chemistry, genomics, cheminformatics, bioinformatics and artificial intelligence.

    Science.gov (United States)

    Maréchal, Eric

    2008-09-01

    Chemogenomics is the study of the interaction of functional biological systems with exogenous small molecules, or in broader sense the study of the intersection of biological and chemical spaces. Chemogenomics requires expertises in biology, chemistry and computational sciences (bioinformatics, cheminformatics, large scale statistics and machine learning methods) but it is more than the simple apposition of each of these disciplines. Biological entities interacting with small molecules can be isolated proteins or more elaborate systems, from single cells to complete organisms. The biological space is therefore analyzed at various postgenomic levels (genomic, transcriptomic, proteomic or any phenotypic level). The space of small molecules is partially real, corresponding to commercial and academic collections of compounds, and partially virtual, corresponding to the chemical space possibly synthesizable. Synthetic chemistry has developed novel strategies allowing a physical exploration of this universe of possibilities. A major challenge of cheminformatics is to charter the virtual space of small molecules using realistic biological constraints (bioavailability, druggability, structural biological information). Chemogenomics is a descendent of conventional pharmaceutical approaches, since it involves the screening of chemolibraries for their effect on biological targets, and benefits from the advances in the corresponding enabling technologies and the introduction of new biological markers. Screening was originally motivated by the rigorous discovery of new drugs, neglecting and throwing away any molecule that would fail to meet the standards required for a therapeutic treatment. It is now the basis for the discovery of small molecules that might or might not be directly used as drugs, but which have an immense potential for basic research, as probes to explore an increasing number of biological phenomena. Concerns about the environmental impact of chemical industry

  17. Identification of genomic biomarkers for anthracycline-induced cardiotoxicity in human iPSC-derived cardiomyocytes: an in vitro repeated exposure toxicity approach for safety assessment.

    Science.gov (United States)

    Chaudhari, Umesh; Nemade, Harshal; Wagh, Vilas; Gaspar, John Antonydas; Ellis, James K; Srinivasan, Sureshkumar Perumal; Spitkovski, Dimitry; Nguemo, Filomain; Louisse, Jochem; Bremer, Susanne; Hescheler, Jürgen; Keun, Hector C; Hengstler, Jan G; Sachinidis, Agapios

    2016-11-01

    The currently available techniques for the safety evaluation of candidate drugs are usually cost-intensive and time-consuming and are often insufficient to predict human relevant cardiotoxicity. The purpose of this study was to develop an in vitro repeated exposure toxicity methodology allowing the identification of predictive genomics biomarkers of functional relevance for drug-induced cardiotoxicity in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). The hiPSC-CMs were incubated with 156 nM doxorubicin, which is a well-characterized cardiotoxicant, for 2 or 6 days followed by washout of the test compound and further incubation in compound-free culture medium until day 14 after the onset of exposure. An xCELLigence Real-Time Cell Analyser was used to monitor doxorubicin-induced cytotoxicity while also monitoring functional alterations of cardiomyocytes by counting of the beating frequency of cardiomyocytes. Unlike single exposure, repeated doxorubicin exposure resulted in long-term arrhythmic beating in hiPSC-CMs accompanied by significant cytotoxicity. Global gene expression changes were studied using microarrays and bioinformatics tools. Analysis of the transcriptomic data revealed early expression signatures of genes involved in formation of sarcomeric structures, regulation of ion homeostasis and induction of apoptosis. Eighty-four significantly deregulated genes related to cardiac functions, stress and apoptosis were validated using real-time PCR. The expression of the 84 genes was further studied by real-time PCR in hiPSC-CMs incubated with daunorubicin and mitoxantrone, further anthracycline family members that are also known to induce cardiotoxicity. A panel of 35 genes was deregulated by all three anthracycline family members and can therefore be expected to predict the cardiotoxicity of compounds acting by similar mechanisms as doxorubicin, daunorubicin or mitoxantrone. The identified gene panel can be applied in the safety

  18. Biomarkers of adverse drug reactions.

    Science.gov (United States)

    Carr, Daniel F; Pirmohamed, Munir

    2018-02-01

    Adverse drug reactions can be caused by a wide range of therapeutics. Adverse drug reactions affect many bodily organ systems and vary widely in severity. Milder adverse drug reactions often resolve quickly following withdrawal of the casual drug or sometimes after dose reduction. Some adverse drug reactions are severe and lead to significant organ/tissue injury which can be fatal. Adverse drug reactions also represent a financial burden to both healthcare providers and the pharmaceutical industry. Thus, a number of stakeholders would benefit from development of new, robust biomarkers for the prediction, diagnosis, and prognostication of adverse drug reactions. There has been significant recent progress in identifying predictive genomic biomarkers with the potential to be used in clinical settings to reduce the burden of adverse drug reactions. These have included biomarkers that can be used to alter drug dose (for example, Thiopurine methyltransferase (TPMT) and azathioprine dose) and drug choice. The latter have in particular included human leukocyte antigen (HLA) biomarkers which identify susceptibility to immune-mediated injuries to major organs such as skin, liver, and bone marrow from a variety of drugs. This review covers both the current state of the art with regard to genomic adverse drug reaction biomarkers. We also review circulating biomarkers that have the potential to be used for both diagnosis and prognosis, and have the added advantage of providing mechanistic information. In the future, we will not be relying on single biomarkers (genomic/non-genomic), but on multiple biomarker panels, integrated through the application of different omics technologies, which will provide information on predisposition, early diagnosis, prognosis, and mechanisms. Impact statement • Genetic and circulating biomarkers present significant opportunities to personalize patient therapy to minimize the risk of adverse drug reactions. ADRs are a significant heath issue

  19. Discursos e vozes na cobertura jornalística das COP15 e 16

    Directory of Open Access Journals (Sweden)

    Ilza Maria Tourinho Girardi

    2013-12-01

    Full Text Available O texto apresenta um exercício de análise da cobertura das Conferências da ONU sobre Mudanças Climáticas, COP 15 e 16, em revistas brasileiras e portuguesas publicadas em 2009 e 2010. Examina como foi construído o discurso sobre sustentabilidade e quais foram as vozes acionadas. Por meio da leitura produzida, teórica e metodologicamente baseada na análise do discurso e das fontes, foi possível evidenciar a predominância de um discurso ecotecnocrático e a opção privilegiada por fontes dos campos político e econômico

  20. Pharmacogenomic Biomarkers

    Directory of Open Access Journals (Sweden)

    Sandra C. Kirkwood

    2002-01-01

    Full Text Available Pharmacogenomic biomarkers hold great promise for the future of medicine and have been touted as a means to personalize prescriptions. Genetic biomarkers for disease susceptibility including both Mendelian and complex disease promise to result in improved understanding of the pathophysiology of disease, identification of new potential therapeutic targets, and improved molecular classification of disease. However essential to fulfilling the promise of individualized therapeutic intervention is the identification of drug activity biomarkers that stratify individuals based on likely response to a particular therapeutic, both positive response, efficacy, and negative response, development of side effect or toxicity. Prior to the widespread clinical application of a genetic biomarker multiple scientific studies must be completed to identify the genetic variants and delineate their functional significance in the pathophysiology of a carefully defined phenotype. The applicability of the genetic biomarker in the human population must then be verified through both retrospective studies utilizing stored or clinical trial samples, and through clinical trials prospectively stratifying patients based on the biomarker. The risk conferred by the polymorphism and the applicability in the general population must be clearly understood. Thus, the development and widespread application of a pharmacogenomic biomarker is an involved process and for most disease states we are just at the beginning of the journey towards individualized therapy and improved clinical outcome.

  1. Meeting Report--NASA Radiation Biomarker Workshop

    Energy Technology Data Exchange (ETDEWEB)

    Straume, Tore; Amundson, Sally A,; Blakely, William F.; Burns, Frederic J.; Chen, Allen; Dainiak, Nicholas; Franklin, Stephen; Leary, Julie A.; Loftus, David J.; Morgan, William F.; Pellmar, Terry C.; Stolc, Viktor; Turteltaub, Kenneth W.; Vaughan, Andrew T.; Vijayakumar, Srinivasan; Wyrobek, Andrew J.

    2008-05-01

    A summary is provided of presentations and discussions from the NASA Radiation Biomarker Workshop held September 27-28, 2007, at NASA Ames Research Center in Mountain View, California. Invited speakers were distinguished scientists representing key sectors of the radiation research community. Speakers addressed recent developments in the biomarker and biotechnology fields that may provide new opportunities for health-related assessment of radiation-exposed individuals, including for long-duration space travel. Topics discussed include the space radiation environment, biomarkers of radiation sensitivity and individual susceptibility, molecular signatures of low-dose responses, multivariate analysis of gene expression, biomarkers in biodefense, biomarkers in radiation oncology, biomarkers and triage following large-scale radiological incidents, integrated and multiple biomarker approaches, advances in whole-genome tiling arrays, advances in mass-spectrometry proteomics, radiation biodosimetry for estimation of cancer risk in a rat skin model, and confounding factors. Summary conclusions are provided at the end of the report.

  2. Genomic, Epigenomic, and Transcriptomic Profiling towards Identifying Omics Features and Specific Biomarkers That Distinguish Uterine Leiomyosarcoma and Leiomyoma at Molecular Levels

    Directory of Open Access Journals (Sweden)

    Tomoko Miyata

    2015-01-01

    Full Text Available Uterine leiomyosarcoma (LMS is the worst malignancy among the gynecologic cancers. Uterine leiomyoma (LM, a benign tumor of myometrial origin, is the most common among women of childbearing age. Because of their similar symptoms, it is difficult to preoperatively distinguish the two conditions only by ultrasound and pelvic MRI. While histopathological diagnosis is currently the main approach used to distinguish them postoperatively, unusual histologic variants of LM tend to be misdiagnosed as LMS. Therefore, development of molecular diagnosis as an alternative or confirmatory means will help to diagnose LMS more accurately. We adopted omics-based technologies to identify genome-wide features to distinguish LMS from LM and revealed that copy number, gene expression, and DNA methylation profiles successfully distinguished these tumors. LMS was found to possess features typically observed in malignant solid tumors, such as extensive chromosomal abnormalities, overexpression of cell cycle-related genes, hypomethylation spreading through large genomic regions, and frequent hypermethylation at the polycomb group target genes and protocadherin genes. We also identified candidate expression and DNA methylation markers, which will facilitate establishing postoperative molecular diagnostic tests based on conventional quantitative assays. Our results demonstrate the feasibility of establishing such tests and the possibility of developing preoperative and noninvasive methods.

  3. LABORATORY BIOMARKERS FOR ANKYLOSING SPONDYLITIS

    Directory of Open Access Journals (Sweden)

    E. N. Aleksandrova

    2017-01-01

    Full Text Available Ankylosing spondylitis (AS is a chronic inflammatory disease from a group of spondyloarthritis (SpA, which is characterized by lesions of the sacroiliac joints and spine with the common involvement of entheses and peripheral joints in the pathological process. Advances in modern laboratory medicine have contributed to a substantial expansion of the range of pathogenetic, diagnostic, and prognostic biomarkers of AS. As of now, there are key pathogenetic biomarkers of AS (therapeutic targets, which include tumor necrosis factor-α (TNF-α, interleukin 17 (IL-17, and IL-23. Among the laboratory diagnostic and prognostic biomarkers, HLA-B27 and C-reactive protein are of the greatest value in clinical practice; the former for the early diagnosis of the disease and the latter for the assessment of disease activity, the risk of radiographic progression and the efficiency of therapy. Anti-CD74 antibodies are a new biomarker that has high sensitivity and specificity values in diagnosing axial SpA at an early stage. A number of laboratory biomarkers, including calprotectin, matrix metalloproteinase-3 (MMP-3, vascular endothelial growth factor, Dickkopf-1 (Dkk-1, and C-terminal telopeptide of type II collagen (CTX II do not well reflect disease activity, but may predict progressive structural changes in the spine and sacroiliac joints in AS. Blood calprotectin level monitoring allows the effective prediction of a response to therapy with TNF inhibitors and anti-IL-17А monoclonal antibodies. The prospects for the laboratory diagnosis of AS are associated with the clinical validation of candidate biomarkers during large-scale prospective cohort studies and with a search for new proteomic, transcriptomic and genomic markers, by using innovative molecular and cellular technologies.

  4. Candidate immune biomarkers for radioimmunotherapy.

    Science.gov (United States)

    Levy, Antonin; Nigro, Giulia; Sansonetti, Philippe J; Deutsch, Eric

    2017-08-01

    Newly available immune checkpoint blockers (ICBs), capable to revert tumor immune tolerance, are revolutionizing the anticancer armamentarium. Recent evidence also established that ionizing radiation (IR) could produce antitumor immune responses, and may as well synergize with ICBs. Multiple radioimmunotherapy combinations are thenceforth currently assessed in early clinical trials. Past examples have highlighted the need for treatment personalization, and there is an unmet need to decipher immunological biomarkers that could allow selecting patients who could benefit from these promising but expensive associations. Recent studies have identified potential predictive and prognostic immune assays at the cellular (tumor microenvironment composition), genomic (mutational/neoantigen load), and peripheral blood levels. Within this review, we collected the available evidence regarding potential personalized immune biomarker-directed radiation therapy strategies that might be used for patient selection in the era of radioimmunotherapy. Copyright © 2017. Published by Elsevier B.V.

  5. Systems biology and biomarker discovery

    Energy Technology Data Exchange (ETDEWEB)

    Rodland, Karin D.

    2010-12-01

    Medical practitioners have always relied on surrogate markers of inaccessible biological processes to make their diagnosis, whether it was the pallor of shock, the flush of inflammation, or the jaundice of liver failure. Obviously, the current implementation of biomarkers for disease is far more sophisticated, relying on highly reproducible, quantitative measurements of molecules that are often mechanistically associated with the disease in question, as in glycated hemoglobin for the diagnosis of diabetes [1] or the presence of cardiac troponins in the blood for confirmation of myocardial infarcts [2]. In cancer, where the initial symptoms are often subtle and the consequences of delayed diagnosis often drastic for disease management, the impetus to discover readily accessible, reliable, and accurate biomarkers for early detection is compelling. Yet despite years of intense activity, the stable of clinically validated, cost-effective biomarkers for early detection of cancer is pathetically small and still dominated by a handful of markers (CA-125, CEA, PSA) first discovered decades ago. It is time, one could argue, for a fresh approach to the discovery and validation of disease biomarkers, one that takes full advantage of the revolution in genomic technologies and in the development of computational tools for the analysis of large complex datasets. This issue of Disease Markers is dedicated to one such new approach, loosely termed the 'Systems Biology of Biomarkers'. What sets the Systems Biology approach apart from other, more traditional approaches, is both the types of data used, and the tools used for data analysis - and both reflect the revolution in high throughput analytical methods and high throughput computing that has characterized the start of the twenty first century.

  6. Tumor antigens as proteogenomic biomarkers in invasive ductal carcinomas

    DEFF Research Database (Denmark)

    Olsen, Lars Rønn; Campos, Benito; Winther, Ole

    2014-01-01

    directly linked to the hallmarks of cancer. The results found by proteogenomic analysis of the 32 tumor antigens studied here, capture largely the same pathway irregularities as those elucidated from large-scale screening of genomics analyses, where several thousands of genes are often found......Background: The majority of genetic biomarkers for human cancers are defined by statistical screening of high-throughput genomics data. While a large number of genetic biomarkers have been proposed for diagnostic and prognostic applications, only a small number have been applied in the clinic....... Similarly, the use of proteomics methods for the discovery of cancer biomarkers is increasing. The emerging field of proteogenomics seeks to enrich the value of genomics and proteomics approaches by studying the intersection of genomics and proteomics data. This task is challenging due to the complex nature...

  7. Combination of biomarkers

    DEFF Research Database (Denmark)

    Thurfjell, Lennart; Lötjönen, Jyrki; Lundqvist, Roger

    2012-01-01

    The New National Institute on Aging-Alzheimer's Association diagnostic guidelines for Alzheimer's disease (AD) incorporate biomarkers in the diagnostic criteria and suggest division of biomarkers into two categories: Aβ accumulation and neuronal degeneration or injury.......The New National Institute on Aging-Alzheimer's Association diagnostic guidelines for Alzheimer's disease (AD) incorporate biomarkers in the diagnostic criteria and suggest division of biomarkers into two categories: Aβ accumulation and neuronal degeneration or injury....

  8. Allergic asthma biomarkers using systems approaches

    Directory of Open Access Journals (Sweden)

    Gaurab eSircar

    2014-01-01

    Full Text Available Asthma is characterized by lung inflammation caused by complex interaction between the immune system and environmental factors such as allergens and inorganic pollutants. Recent research in this field is focused on discovering new biomarkers associated with asthma pathogenesis. This review illustrates updated research associating biomarkers of allergic asthma and their potential use in systems biology of the disease. We focus on biomolecules with altered expression, which may serve as inflammatory, diagnostic and therapeutic biomarkers of asthma discovered in human or experimental asthma model using genomic, proteomic and epigenomic approaches for gene and protein expression profiling. These include high-throughput technologies such as state of the art microarray and proteomics Mass Spectrometry (MS platforms. Emerging concepts of molecular interactions and pathways may provide new insights in searching potential clinical biomarkers. We summarized certain pathways with significant linkage to asthma pathophysiology by analyzing the compiled biomarkers. Systems approaches with this data can identify the regulating networks, which will eventually identify the key biomarkers to be used for diagnostics and drug discovery.

  9. Multiomics Data Triangulation for Asthma Candidate Biomarkers and Precision Medicine.

    Science.gov (United States)

    Pecak, Matija; Korošec, Peter; Kunej, Tanja

    2018-06-01

    Asthma is a common complex disorder and has been subject to intensive omics research for disease susceptibility and therapeutic innovation. Candidate biomarkers of asthma and its precision treatment demand that they stand the test of multiomics data triangulation before they can be prioritized for clinical applications. We classified the biomarkers of asthma after a search of the literature and based on whether or not a given biomarker candidate is reported in multiple omics platforms and methodologies, using PubMed and Web of Science, we identified omics studies of asthma conducted on diverse platforms using keywords, such as asthma, genomics, metabolomics, and epigenomics. We extracted data about asthma candidate biomarkers from 73 articles and developed a catalog of 190 potential asthma biomarkers (167 human, 23 animal data), comprising DNA loci, transcripts, proteins, metabolites, epimutations, and noncoding RNAs. The data were sorted according to 13 omics types: genomics, epigenomics, transcriptomics, proteomics, interactomics, metabolomics, ncRNAomics, glycomics, lipidomics, environmental omics, pharmacogenomics, phenomics, and integrative omics. Importantly, we found that 10 candidate biomarkers were apparent in at least two or more omics levels, thus promising potential for further biomarker research and development and precision medicine applications. This multiomics catalog reported herein for the first time contributes to future decision-making on prioritization of biomarkers and validation efforts for precision medicine in asthma. The findings may also facilitate meta-analyses and integrative omics studies in the future.

  10. Oral Metagenomic Biomarkers in Rheumatoid Arthritis

    Science.gov (United States)

    2017-09-01

    individuals with rheumatoid arthritis (RA). The goal is to test the  hypothesis that oral microbiome and metagenomic analyses will allow  us  to identify new...biomarkers  that are  useful  for the diagnosis of early RA and/or biomarkers that help to predict the efficacy of  specific therapeutic interventions... RNA  microbiome analysis as well as whole genome shotgun sequencing.  Upon completion of these aims, any identified bacterial biomarkers may be

  11. Cardiac biomarkers in Neonatology

    OpenAIRE

    Vijlbrief, D.C.

    2015-01-01

    In this thesis, the role for cardiac biomarkers in neonatology was investigated. Several clinically relevant results were reported. In term and preterm infants, hypoxia and subsequent adaptation play an important role in cardiac biomarker elevation. The elevated natriuretic peptides are indicative of abnormal function; elevated troponins are suggestive for cardiomyocyte damage. This methodology makes these biomarkers of additional value in the treatment of newborn infants, separate or as a co...

  12. Potential Peripheral Biomarkers for the Diagnosis of Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Seema Patel

    2011-01-01

    Full Text Available Advances in the discovery of a peripheral biomarker for the diagnosis of Alzheimer's would provide a way to better detect the onset of this debilitating disease in a manner that is both noninvasive and universally available. This paper examines the current approaches that are being used to discover potential biomarker candidates available in the periphery. The search for a peripheral biomarker that could be utilized diagnostically has resulted in an extensive amount of studies that employ several biological approaches, including the assessment of tissues, genomics, proteomics, epigenetics, and metabolomics. Although a definitive biomarker has yet to be confirmed, advances in the understanding of the mechanisms of the disease and major susceptibility factors have been uncovered and reveal promising possibilities for the future discovery of a useful biomarker.

  13. Biology and Biomarkers for Wound Healing

    Science.gov (United States)

    Lindley, Linsey E.; Stojadinovic, Olivera; Pastar, Irena; Tomic-Canic, Marjana

    2016-01-01

    Background As the population grows older, the incidence and prevalence of conditions which lead to a predisposition for poor wound healing also increases. Ultimately, this increase in non-healing wounds has led to significant morbidity and mortality with subsequent huge economic ramifications. Therefore, understanding specific molecular mechanisms underlying aberrant wound healing is of great importance. It has, and will continue to be the leading pathway to the discovery of therapeutic targets as well as diagnostic molecular biomarkers. Biomarkers may help identify and stratify subsets of non-healing patients for whom biomarker-guided approaches may aid in healing. Methods A series of literature searches were performed using Medline, PubMed, Cochrane Library, and Internet searches. Results Currently, biomarkers are being identified using biomaterials sourced locally, from human wounds and/or systemically using systematic high-throughput “omics” modalities (genomic, proteomic, lipidomic, metabolomic analysis). In this review we highlight the current status of clinically applicable biomarkers and propose multiple steps in validation and implementation spectrum including those measured in tissue specimens e.g. β-catenin and c-myc, wound fluid e.g. MMP’s and interleukins, swabs e.g. wound microbiota and serum e.g. procalcitonin and MMP’s. Conclusions Identification of numerous potential biomarkers utilizing different avenues of sample collection and molecular approaches is currently underway. A focus on simplicity, and consistent implementation of these biomarkers as well as an emphasis on efficacious follow-up therapeutics is necessary for transition of this technology to clinically feasible point-of-care applications. PMID:27556760

  14. Biomarkers for bladder cancer management: present and future

    Science.gov (United States)

    Ye, Fei; Wang, Li; Castillo-Martin, Mireia; McBride, Russell; Galsky, Matthew D; Zhu, Jun; Boffetta, Paolo; Zhang, David Y; Cordon-Cardo, Carlos

    2014-01-01

    Accurate and sensitive detection of bladder cancer is critical to diagnose this deadly disease at an early stage, estimate prognosis, predict response to treatment, and monitor recurrence. In past years, laboratory diagnosis and surveillance of urinary bladder cancer have improved significantly. Although urine cytology remains the gold standard test, many new urinary biomarkers have been identified. Furthermore, recent advances in genomic studies of bladder cancer have helped to refine our understanding of the pathogenesis of the disease, the biological basis for outcome disparities, and to inform more efficient treatment and surveillance strategies. In this article, the established diagnostic tests, newly identified biomarkers and genomic landscape of bladder cancer will be reviewed. PMID:25374904

  15. Biomarkers in Autism

    Directory of Open Access Journals (Sweden)

    Robert eHendren

    2014-08-01

    Full Text Available Autism spectrum disorders (ASD are complex, heterogeneous disorders caused by an interaction between genetic vulnerability and environmental factors. In an effort to better target the underlying roots of ASD for diagnosis and treatment, efforts to identify reliable biomarkers in genetics, neuroimaging, gene expression and measures of the body’s metabolism are growing. For this article, we review the published studies of potential biomarkers in autism and conclude that while there is increasing promise of finding biomarkers that can help us target treatment, there are none with enough evidence to support routine clinical use unless medical illness is suspected. Promising biomarkers include those for mitochondrial function, oxidative stress, and immune function. Genetic clusters are also suggesting the potential for useful biomarkers.

  16. Prognostic biomarkers in osteoarthritis

    Science.gov (United States)

    Attur, Mukundan; Krasnokutsky-Samuels, Svetlana; Samuels, Jonathan; Abramson, Steven B.

    2013-01-01

    Purpose of review Identification of patients at risk for incident disease or disease progression in osteoarthritis remains challenging, as radiography is an insensitive reflection of molecular changes that presage cartilage and bone abnormalities. Thus there is a widely appreciated need for biochemical and imaging biomarkers. We describe recent developments with such biomarkers to identify osteoarthritis patients who are at risk for disease progression. Recent findings The biochemical markers currently under evaluation include anabolic, catabolic, and inflammatory molecules representing diverse biological pathways. A few promising cartilage and bone degradation and synthesis biomarkers are in various stages of development, awaiting further validation in larger populations. A number of studies have shown elevated expression levels of inflammatory biomarkers, both locally (synovial fluid) and systemically (serum and plasma). These chemical biomarkers are under evaluation in combination with imaging biomarkers to predict early onset and the burden of disease. Summary Prognostic biomarkers may be used in clinical knee osteoarthritis to identify subgroups in whom the disease progresses at different rates. This could facilitate our understanding of the pathogenesis and allow us to differentiate phenotypes within a heterogeneous knee osteoarthritis population. Ultimately, such findings may help facilitate the development of disease-modifying osteoarthritis drugs (DMOADs). PMID:23169101

  17. Impact of age, BMI and HbA1c levels on the genome-wide DNA methylation and mRNA expression patterns in human adipose tissue and identification of epigenetic biomarkers in blood

    DEFF Research Database (Denmark)

    Rönn, Tina; Volkov, Petr; Gillberg, Linn

    2015-01-01

    Increased age, BMI and HbA1c levels are risk factors for several non-communicable diseases. However, the impact of these factors on the genome-wide DNA methylation pattern in human adipose tissue remains unknown. We analyzed the DNA methylation of ∼480 000 sites in human adipose tissue from 96 ma...

  18. Biomarkers in Airway Diseases

    Directory of Open Access Journals (Sweden)

    Janice M Leung

    2013-01-01

    Full Text Available The inherent limitations of spirometry and clinical history have prompted clinicians and scientists to search for surrogate markers of airway diseases. Although few biomarkers have been widely accepted into the clinical armamentarium, the authors explore three sources of biomarkers that have shown promise as indicators of disease severity and treatment response. In asthma, exhaled nitric oxide measurements can predict steroid responsiveness and sputum eosinophil counts have been used to titrate anti-inflammatory therapies. In chronic obstructive pulmonary disease, inflammatory plasma biomarkers, such as fibrinogen, club cell secretory protein-16 and surfactant protein D, can denote greater severity and predict the risk of exacerbations. While the multitude of disease phenotypes in respiratory medicine make biomarker development especially challenging, these three may soon play key roles in the diagnosis and management of airway diseases.

  19. amphibian_biomarker_data

    Data.gov (United States)

    U.S. Environmental Protection Agency — Amphibian metabolite data used in Snyder, M.N., Henderson, W.M., Glinski, D.G., Purucker, S. T., 2017. Biomarker analysis of american toad (Anaxyrus americanus) and...

  20. Validation of New Cancer Biomarkers

    DEFF Research Database (Denmark)

    Duffy, Michael J; Sturgeon, Catherine M; Söletormos, Georg

    2015-01-01

    BACKGROUND: Biomarkers are playing increasingly important roles in the detection and management of patients with cancer. Despite an enormous number of publications on cancer biomarkers, few of these biomarkers are in widespread clinical use. CONTENT: In this review, we discuss the key steps...... in advancing a newly discovered cancer candidate biomarker from pilot studies to clinical application. Four main steps are necessary for a biomarker to reach the clinic: analytical validation of the biomarker assay, clinical validation of the biomarker test, demonstration of clinical value from performance...... of the biomarker test, and regulatory approval. In addition to these 4 steps, all biomarker studies should be reported in a detailed and transparent manner, using previously published checklists and guidelines. Finally, all biomarker studies relating to demonstration of clinical value should be registered before...

  1. Discovering Alzheimer Genetic Biomarkers Using Bayesian Networks

    Directory of Open Access Journals (Sweden)

    Fayroz F. Sherif

    2015-01-01

    Full Text Available Single nucleotide polymorphisms (SNPs contribute most of the genetic variation to the human genome. SNPs associate with many complex and common diseases like Alzheimer’s disease (AD. Discovering SNP biomarkers at different loci can improve early diagnosis and treatment of these diseases. Bayesian network provides a comprehensible and modular framework for representing interactions between genes or single SNPs. Here, different Bayesian network structure learning algorithms have been applied in whole genome sequencing (WGS data for detecting the causal AD SNPs and gene-SNP interactions. We focused on polymorphisms in the top ten genes associated with AD and identified by genome-wide association (GWA studies. New SNP biomarkers were observed to be significantly associated with Alzheimer’s disease. These SNPs are rs7530069, rs113464261, rs114506298, rs73504429, rs7929589, rs76306710, and rs668134. The obtained results demonstrated the effectiveness of using BN for identifying AD causal SNPs with acceptable accuracy. The results guarantee that the SNP set detected by Markov blanket based methods has a strong association with AD disease and achieves better performance than both naïve Bayes and tree augmented naïve Bayes. Minimal augmented Markov blanket reaches accuracy of 66.13% and sensitivity of 88.87% versus 61.58% and 59.43% in naïve Bayes, respectively.

  2. Comprehensive Genomic Profiling Facilitates Implementation of the National Comprehensive Cancer Network Guidelines for Lung Cancer Biomarker Testing and Identifies Patients Who May Benefit From Enrollment in Mechanism-Driven Clinical Trials.

    Science.gov (United States)

    Suh, James H; Johnson, Adrienne; Albacker, Lee; Wang, Kai; Chmielecki, Juliann; Frampton, Garrett; Gay, Laurie; Elvin, Julia A; Vergilio, Jo-Anne; Ali, Siraj; Miller, Vincent A; Stephens, Philip J; Ross, Jeffrey S

    2016-06-01

    The National Comprehensive Cancer Network (NCCN) guidelines for patients with metastatic non-small cell lung cancer (NSCLC) recommend testing for EGFR, BRAF, ERBB2, and MET mutations; ALK, ROS1, and RET rearrangements; and MET amplification. We investigated the feasibility and utility of comprehensive genomic profiling (CGP), a hybrid capture-based next-generation sequencing (NGS) test, in clinical practice. CGP was performed to a mean coverage depth of 576× on 6,832 consecutive cases of NSCLC (2012-2015). Genomic alterations (GAs) (point mutations, small indels, copy number changes, and rearrangements) involving EGFR, ALK, BRAF, ERBB2, MET, ROS1, RET, and KRAS were recorded. We also evaluated lung adenocarcinoma (AD) cases without GAs, involving these eight genes. The median age of the patients was 64 years (range: 13-88 years) and 53% were female. Among the patients studied, 4,876 (71%) harbored at least one GA involving EGFR (20%), ALK (4.1%), BRAF (5.7%), ERBB2 (6.0%), MET (5.6%), ROS1 (1.5%), RET (2.4%), or KRAS (32%). In the remaining cohort of lung AD without these known drivers, 273 cancer-related genes were altered in at least 0.1% of cases, including STK11 (21%), NF1 (13%), MYC (9.8%), RICTOR (6.4%), PIK3CA (5.4%), CDK4 (4.3%), CCND1 (4.0%), BRCA2 (2.5%), NRAS (2.3%), BRCA1 (1.7%), MAP2K1 (1.2%), HRAS (0.7%), NTRK1 (0.7%), and NTRK3 (0.2%). CGP is practical and facilitates implementation of the NCCN guidelines for NSCLC by enabling simultaneous detection of GAs involving all seven driver oncogenes and KRAS. Furthermore, without additional tissue use or cost, CGP identifies patients with "pan-negative" lung AD who may benefit from enrollment in mechanism-driven clinical trials. National Comprehensive Cancer Network guidelines for patients with metastatic non-small cell lung cancer (NSCLC) recommend testing for several genomic alterations (GAs). The feasibility and utility of comprehensive genomic profiling were studied in NSCLC and in lung adenocarcinoma

  3. Biomarkers of sepsis

    Science.gov (United States)

    2013-01-01

    Sepsis is an unusual systemic reaction to what is sometimes an otherwise ordinary infection, and it probably represents a pattern of response by the immune system to injury. A hyper-inflammatory response is followed by an immunosuppressive phase during which multiple organ dysfunction is present and the patient is susceptible to nosocomial infection. Biomarkers to diagnose sepsis may allow early intervention which, although primarily supportive, can reduce the risk of death. Although lactate is currently the most commonly used biomarker to identify sepsis, other biomarkers may help to enhance lactate’s effectiveness; these include markers of the hyper-inflammatory phase of sepsis, such as pro-inflammatory cytokines and chemokines; proteins such as C-reactive protein and procalcitonin which are synthesized in response to infection and inflammation; and markers of neutrophil and monocyte activation. Recently, markers of the immunosuppressive phase of sepsis, such as anti-inflammatory cytokines, and alterations of the cell surface markers of monocytes and lymphocytes have been examined. Combinations of pro- and anti-inflammatory biomarkers in a multi-marker panel may help identify patients who are developing severe sepsis before organ dysfunction has advanced too far. Combined with innovative approaches to treatment that target the immunosuppressive phase, these biomarkers may help to reduce the mortality rate associated with severe sepsis which, despite advances in supportive measures, remains high. PMID:23480440

  4. Mass spectrometry for biomarker development

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Chaochao; Liu, Tao; Baker, Erin Shammel; Rodland, Karin D.; Smith, Richard D.

    2015-06-19

    Biomarkers potentially play a crucial role in early disease diagnosis, prognosis and targeted therapy. In the past decade, mass spectrometry based proteomics has become increasingly important in biomarker development due to large advances in technology and associated methods. This chapter mainly focuses on the application of broad (e.g. shotgun) proteomics in biomarker discovery and the utility of targeted proteomics in biomarker verification and validation. A range of mass spectrometry methodologies are discussed emphasizing their efficacy in the different stages in biomarker development, with a particular emphasis on blood biomarker development.

  5. Biomarkers of the Dementia

    Directory of Open Access Journals (Sweden)

    Mikio Shoji

    2011-01-01

    Full Text Available Recent advances in biomarker studies on dementia are summarized here. CSF Aβ40, Aβ42, total tau, and phosphorylated tau are the most sensitive biomarkers for diagnosis of Alzheimer's disease (AD and prediction of onset of AD from mild cognitive impairment (MCI. Based on this progress, new diagnostic criteria for AD, MCI, and preclinical AD were proposed by National Institute of Aging (NIA and Alzheimer's Association in August 2010. In these new criteria, progress in biomarker identification and amyloid imaging studies in the past 10 years have added critical information. Huge contributions of basic and clinical studies have established clinical evidence supporting these markers. Based on this progress, essential therapy for cure of AD is urgently expected.

  6. Inflammatory biomarkers and cancer

    DEFF Research Database (Denmark)

    Rasmussen, Line Jee Hartmann; Schultz, Martin; Gaardsting, Anne

    2017-01-01

    and previous cancer diagnoses compared to patients who were not diagnosed with cancer. Previous cancer, C-reactive protein (CRP) and suPAR were significantly associated with newly diagnosed cancer during follow-up in multiple logistic regression analyses adjusted for age, sex and CRP. Neither any of the PRRs......In Denmark, patients with serious nonspecific symptoms and signs of cancer (NSSC) are referred to the diagnostic outpatient clinics (DOCs) where an accelerated cancer diagnostic program is initiated. Various immunological and inflammatory biomarkers have been associated with cancer, including...... soluble urokinase plasminogen activator receptor (suPAR) and the pattern recognition receptors (PRRs) pentraxin-3, mannose-binding lectin, ficolin-1, ficolin-2 and ficolin-3. We aimed to evaluate these biomarkers and compare their diagnostic ability to classical biomarkers for diagnosing cancer...

  7. Biomarkers for anorexia nervosa

    DEFF Research Database (Denmark)

    Sjøgren, Jan Magnus

    2017-01-01

    Biomarkers for anorexia nervosa (AN) which reflect the pathophysiology and relate to the aetiology of the disease, are warranted and could bring us one step closer to targeted treatment of AN. Some leads may be found in the biochemistry which often is found disturbed in AN, although normalization...

  8. Curated compendium of human transcriptional biomarker data.

    Science.gov (United States)

    Golightly, Nathan P; Bell, Avery; Bischoff, Anna I; Hollingsworth, Parker D; Piccolo, Stephen R

    2018-04-17

    One important use of genome-wide transcriptional profiles is to identify relationships between transcription levels and patient outcomes. These translational insights can guide the development of biomarkers for clinical application. Data from thousands of translational-biomarker studies have been deposited in public repositories, enabling reuse. However, data-reuse efforts require considerable time and expertise because transcriptional data are generated using heterogeneous profiling technologies, preprocessed using diverse normalization procedures, and annotated in non-standard ways. To address this problem, we curated 45 publicly available, translational-biomarker datasets from a variety of human diseases. To increase the data's utility, we reprocessed the raw expression data using a uniform computational pipeline, addressed quality-control problems, mapped the clinical annotations to a controlled vocabulary, and prepared consistently structured, analysis-ready data files. These data, along with scripts we used to prepare the data, are available in a public repository. We believe these data will be particularly useful to researchers seeking to perform benchmarking studies-for example, to compare and optimize machine-learning algorithms' ability to predict biomedical outcomes.

  9. Individual Biomarkers Using Molecular Personalized Medicine Approaches.

    Science.gov (United States)

    Zenner, Hans P

    2017-01-01

    Molecular personalized medicine tries to generate individual predictive biomarkers to assist doctors in their decision making. These are thought to improve the efficacy and lower the toxicity of a treatment. The molecular basis of the desired high-precision prediction is modern "omex" technologies providing high-throughput bioanalytical methods. These include genomics and epigenomics, transcriptomics, proteomics, metabolomics, microbiomics, imaging, and functional analyses. In most cases, producing big data also requires a complex biomathematical analysis. Using molecular personalized medicine, the conventional physician's check of biomarker results may no longer be sufficient. By contrast, the physician may need to cooperate with the biomathematician to achieve the desired prediction on the basis of the analysis of individual big data typically produced by omex technologies. Identification of individual biomarkers using molecular personalized medicine approaches is thought to allow a decision-making for the precise use of a targeted therapy, selecting the successful therapeutic tool from a panel of preexisting drugs or medical products. This should avoid the treatment of nonresponders and responders that produces intolerable unwanted effects. © 2017 S. Karger AG, Basel.

  10. Tissue- and Serum-Associated Biomarkers of Hepatocellular Carcinoma

    Science.gov (United States)

    Chauhan, Ranjit; Lahiri, Nivedita

    2016-01-01

    Hepatocellular carcinoma (HCC), one of the leading causes of cancer deaths in the world, is offering a challenge to human beings, with the current modes of treatment being a palliative approach. Lack of proper curative or preventive treatment methods encouraged extensive research around the world with an aim to detect a vaccine or therapeutic target biomolecule that could lead to development of a drug or vaccine against HCC. Biomarkers or biological disease markers have emerged as a potential tool as drug/vaccine targets, as they can accurately diagnose, predict, and even prevent the diseases. Biomarker expression in tissue, serum, plasma, or urine can detect tumor in very early stages of its development and monitor the cancer progression and also the effect of therapeutic interventions. Biomarker discoveries are driven by advanced techniques, such as proteomics, transcriptomics, whole genome sequencing, micro- and micro-RNA arrays, and translational clinics. In this review, an overview of the potential of tissue- and serum-associated HCC biomarkers as diagnostic, prognostic, and therapeutic targets for drug development is presented. In addition, we highlight recently developed micro-RNA, long noncoding RNA biomarkers, and single-nucleotide changes, which may be used independently or as complementary biomarkers. These active investigations going on around the world aimed at conquering HCC might show a bright light in the near future. PMID:27398029

  11. Tissue- and Serum-Associated Biomarkers of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Ranjit Chauhan

    2016-01-01

    Full Text Available Hepatocellular carcinoma (HCC, one of the leading causes of cancer deaths in the world, is offering a challenge to human beings, with the current modes of treatment being a palliative approach. Lack of proper curative or preventive treatment methods encouraged extensive research around the world with an aim to detect a vaccine or therapeutic target biomolecule that could lead to development of a drug or vaccine against HCC. Biomarkers or biological disease markers have emerged as a potential tool as drug/vaccine targets, as they can accurately diagnose, predict, and even prevent the diseases. Biomarker expression in tissue, serum, plasma, or urine can detect tumor in very early stages of its development and monitor the cancer progression and also the effect of therapeutic interventions. Biomarker discoveries are driven by advanced techniques, such as proteomics, transcriptomics, whole genome sequencing, micro- and micro-RNA arrays, and translational clinics. In this review, an overview of the potential of tissue- and serum-associated HCC biomarkers as diagnostic, prognostic, and therapeutic targets for drug development is presented. In addition, we highlight recently developed micro-RNA, long noncoding RNA biomarkers, and single-nucleotide changes, which may be used independently or as complementary biomarkers. These active investigations going on around the world aimed at conquering HCC might show a bright light in the near future.

  12. Biomarkers of cancer cachexia.

    Science.gov (United States)

    Loumaye, Audrey; Thissen, Jean-Paul

    2017-12-01

    Cachexia is a complex multifactorial syndrome, characterized by loss of skeletal muscle and fat mass, which affects the majority of advanced cancer patients and is associated with poor prognosis. Interestingly, reversing muscle loss in animal models of cancer cachexia leads to prolong survival. Therefore, detecting cachexia and maintaining muscle mass represent a major goal in the care of cancer patients. However, early diagnosis of cancer cachexia is currently limited for several reasons. Indeed, cachexia development is variable according to tumor and host characteristics. In addition, safe, accessible and non-invasive tools to detect skeletal muscle atrophy are desperately lacking in clinical practice. Finally, the precise molecular mechanisms and the key players involved in cancer cachexia remain poorly characterized. The need for an early diagnosis of cancer cachexia supports therefore the quest for a biomarker that might reflect skeletal muscle atrophy process. Current research offers different promising ways to identify such a biomarker. Initially, the quest for a biomarker of cancer cachexia has mostly focused on mediators of muscle atrophy, produced by both tumor and host, in an attempt to define new therapeutic approaches. In another hand, molecules released by the muscle into the circulation during the atrophy process have been also considered as potential biomarkers. More recently, several "omics" studies are emerging to identify new muscular or circulating markers of cancer cachexia. Some genetic markers could also contribute to identify patients more susceptible to develop cachexia. This article reviews our current knowledge regarding potential biomarkers of cancer cachexia. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  13. An OMIC biomarker detection algorithm TriVote and its application in methylomic biomarker detection.

    Science.gov (United States)

    Xu, Cheng; Liu, Jiamei; Yang, Weifeng; Shu, Yayun; Wei, Zhipeng; Zheng, Weiwei; Feng, Xin; Zhou, Fengfeng

    2018-04-01

    Transcriptomic and methylomic patterns represent two major OMIC data sources impacted by both inheritable genetic information and environmental factors, and have been widely used as disease diagnosis and prognosis biomarkers. Modern transcriptomic and methylomic profiling technologies detect the status of tens of thousands or even millions of probing residues in the human genome, and introduce a major computational challenge for the existing feature selection algorithms. This study proposes a three-step feature selection algorithm, TriVote, to detect a subset of transcriptomic or methylomic residues with highly accurate binary classification performance. TriVote outperforms both filter and wrapper feature selection algorithms with both higher classification accuracy and smaller feature number on 17 transcriptomes and two methylomes. Biological functions of the methylome biomarkers detected by TriVote were discussed for their disease associations. An easy-to-use Python package is also released to facilitate the further applications.

  14. CURRENT APPROACHES FOR RESEARCH OF MULTIPLE SCLEROSIS BIOMARKERS

    Directory of Open Access Journals (Sweden)

    Kolyada T.I

    2016-12-01

    Full Text Available Current data concerning features of multiple sclerosis (MS etiology, pathogenesis, clinical course and treatment of disease indicate the necessity of personalized approach to the management of MS patients. These features are the variety of possible etiological factors and mechanisms that trigger the development of MS, different courses of disease, and significant differences in treatment efficiency. Phenotypic and pathogenetic heterogeneity of MS requires, on the one hand, the stratification of patients into groups with different treatment depending on a number of criteria including genetic characteristics, disease course, stage of the pathological process, and forms of the disease. On the other hand, it requires the use of modern methods for assessment of individual risk of developing MS, its early diagnosis, evaluation and prognosis of the disease course and the treatment efficiency. This approach is based on the identification and determination of biomarkers of MS including the use of systems biology technology platforms such as genomics, proteomics, metabolomics and bioinformatics. Research and practical use of biomarkers of MS in clinical and laboratory practice requires the use of a wide range of modern medical and biological, mathematical and physicochemical methods. The group of "classical" methods used to study MS biomarkers includes physicochemical and immunological methods aimed at the selection and identification of single molecular biomarkers, as well as methods of molecular genetic analysis. This group of methods includes ELISA, western blotting, isoelectric focusing, immunohistochemical methods, flow cytometry, spectrophotometric and nephelometric methods. These techniques make it possible to carry out both qualitative and quantitative assay of molecular biomarkers. The group of "classical methods" can also include methods based on polymerase chain reaction (including multiplex and allele-specific PCR and genome sequencing

  15. Biomarkers of Pediatric Brain Tumors

    Directory of Open Access Journals (Sweden)

    Mark D Russell

    2013-03-01

    Full Text Available Background and Need for Novel Biomarkers: Brain tumors are the leading cause of death by solid tumors in children. Although improvements have been made in their radiological detection and treatment, our capacity to promptly diagnose pediatric brain tumors in their early stages remains limited. This contrasts several other cancers where serum biomarkers such as CA 19-9 and CA 125 facilitate early diagnosis and treatment. Aim: The aim of this article is to review the latest literature and highlight biomarkers which may be of clinical use in the common types of primary pediatric brain tumor. Methods: A PubMed search was performed to identify studies reporting biomarkers in the bodily fluids of pediatric patients with brain tumors. Details regarding the sample type (serum, cerebrospinal fluid or urine, biomarkers analyzed, methodology, tumor type and statistical significance were recorded. Results: A total of 12 manuscripts reporting 19 biomarkers in 367 patients vs. 397 controls were identified in the literature. Of the 19 biomarkers identified, 12 were isolated from cerebrospinal fluid, 2 from serum, 3 from urine, and 2 from multiple bodily fluids. All but one study reported statistically significant differences in biomarker expression between patient and control groups.Conclusions: This review identifies a panel of novel biomarkers for pediatric brain tumors. It provides a platform for the further studies necessary to validate these biomarkers and, in addition, highlights several techniques through which new biomarkers can be discovered.

  16. Extreme genomes

    OpenAIRE

    DeLong, Edward F

    2000-01-01

    The complete genome sequence of Thermoplasma acidophilum, an acid- and heat-loving archaeon, has recently been reported. Comparative genomic analysis of this 'extremophile' is providing new insights into the metabolic machinery, ecology and evolution of thermophilic archaea.

  17. Novel biomarkers for sepsis

    DEFF Research Database (Denmark)

    Larsen, Frederik Fruergaard; Petersen, J Asger

    2017-01-01

    BACKGROUND: Sepsis is a prevalent condition among hospitalized patients that carries a high risk of morbidity and mortality. Rapid recognition of sepsis as the cause of deterioration is desirable, so effective treatment can be initiated rapidly. Traditionally, diagnosis was based on presence of two...... or more positive SIRS criteria due to infection. However, recently published sepsis-3 criteria put more emphasis on organ dysfunction caused by infection in the definition of sepsis. Regardless of this, no gold standard for diagnosis exist, and clinicians still rely on a number of traditional and novel...... biomarkers to discriminate between patients with and without infection, as the cause of deterioration. METHOD: Narrative review of current literature. RESULTS: A number of the most promising biomarkers for diagnoses and prognostication of sepsis are presented. CONCLUSION: Procalcitonin, presepsin, CD64, su...

  18. Mass spectrometry for protein quantification in biomarker discovery.

    Science.gov (United States)

    Wang, Mu; You, Jinsam

    2012-01-01

    Major technological advances have made proteomics an extremely active field for biomarker discovery in recent years due primarily to the development of newer mass spectrometric technologies and the explosion in genomic and protein bioinformatics. This leads to an increased emphasis on larger scale, faster, and more efficient methods for detecting protein biomarkers in human tissues, cells, and biofluids. Most current proteomic methodologies for biomarker discovery, however, are not highly automated and are generally labor-intensive and expensive. More automation and improved software programs capable of handling a large amount of data are essential to reduce the cost of discovery and to increase throughput. In this chapter, we discuss and describe mass spectrometry-based proteomic methods for quantitative protein analysis.

  19. DNA methylation based biomarkers: Practical considerations and applications

    DEFF Research Database (Denmark)

    Nielsen, Helene Myrtue; How Kit, Alexandre; Tost, Jorg

    2012-01-01

    of biochemical molecules such as proteins, DNA, RNA or lipids, whereby protein biomarkers have been the most extensively studied and used, notably in blood-based protein quantification tests or immunohistochemistry. The rise of interest in epigenetic mechanisms has allowed the identification of a new type...... of biomarker, DNA methylation, which is of great potential for many applications. This stable and heritable covalent modification mostly affects cytosines in the context of a CpG dinucleotide in humans. It can be detected and quantified by a number of technologies including genome-wide screening methods...... as well as locus- or gene-specific high-resolution analysis in different types of samples such as frozen tissues and FFPE samples, but also in body fluids such as urine, plasma, and serum obtained through non-invasive procedures. In some cases, DNA methylation based biomarkers have proven to be more...

  20. Grass genomes

    OpenAIRE

    Bennetzen, Jeffrey L.; SanMiguel, Phillip; Chen, Mingsheng; Tikhonov, Alexander; Francki, Michael; Avramova, Zoya

    1998-01-01

    For the most part, studies of grass genome structure have been limited to the generation of whole-genome genetic maps or the fine structure and sequence analysis of single genes or gene clusters. We have investigated large contiguous segments of the genomes of maize, sorghum, and rice, primarily focusing on intergenic spaces. Our data indicate that much (>50%) of the maize genome is composed of interspersed repetitive DNAs, primarily nested retrotransposons that in...

  1. Quantitative imaging as cancer biomarker

    Science.gov (United States)

    Mankoff, David A.

    2015-03-01

    The ability to assay tumor biologic features and the impact of drugs on tumor biology is fundamental to drug development. Advances in our ability to measure genomics, gene expression, protein expression, and cellular biology have led to a host of new targets for anticancer drug therapy. In translating new drugs into clinical trials and clinical practice, these same assays serve to identify patients most likely to benefit from specific anticancer treatments. As cancer therapy becomes more individualized and targeted, there is an increasing need to characterize tumors and identify therapeutic targets to select therapy most likely to be successful in treating the individual patient's cancer. Thus far assays to identify cancer therapeutic targets or anticancer drug pharmacodynamics have been based upon in vitro assay of tissue or blood samples. Advances in molecular imaging, particularly PET, have led to the ability to perform quantitative non-invasive molecular assays. Imaging has traditionally relied on structural and anatomic features to detect cancer and determine its extent. More recently, imaging has expanded to include the ability to image regional biochemistry and molecular biology, often termed molecular imaging. Molecular imaging can be considered an in vivo assay technique, capable of measuring regional tumor biology without perturbing it. This makes molecular imaging a unique tool for cancer drug development, complementary to traditional assay methods, and a potentially powerful method for guiding targeted therapy in clinical trials and clinical practice. The ability to quantify, in absolute measures, regional in vivo biologic parameters strongly supports the use of molecular imaging as a tool to guide therapy. This review summarizes current and future applications of quantitative molecular imaging as a biomarker for cancer therapy, including the use of imaging to (1) identify patients whose tumors express a specific therapeutic target; (2) determine

  2. Population-Sequencing as a Biomarker of Burkholderia mallei and Burkholderia pseudomallei Evolution through Microbial Forensic Analysis

    Directory of Open Access Journals (Sweden)

    John P. Jakupciak

    2013-01-01

    Full Text Available Large-scale genomics projects are identifying biomarkers to detect human disease. B. pseudomallei and B. mallei are two closely related select agents that cause melioidosis and glanders. Accurate characterization of metagenomic samples is dependent on accurate measurements of genetic variation between isolates with resolution down to strain level. Often single biomarker sensitivity is augmented by use of multiple or panels of biomarkers. In parallel with single biomarker validation, advances in DNA sequencing enable analysis of entire genomes in a single run: population-sequencing. Potentially, direct sequencing could be used to analyze an entire genome to serve as the biomarker for genome identification. However, genome variation and population diversity complicate use of direct sequencing, as well as differences caused by sample preparation protocols including sequencing artifacts and mistakes. As part of a Department of Homeland Security program in bacterial forensics, we examined how to implement whole genome sequencing (WGS analysis as a judicially defensible forensic method for attributing microbial sample relatedness; and also to determine the strengths and limitations of whole genome sequence analysis in a forensics context. Herein, we demonstrate use of sequencing to provide genetic characterization of populations: direct sequencing of populations.

  3. [Biomarkers of Alzheimer disease].

    Science.gov (United States)

    Rachel, Wojciech; Grela, Agatha; Zyss, Tomasz; Zieba, Andrzej; Piekoszewski, Wojciech

    2014-01-01

    Cognitive impairment is one of the most abundant age-related psychiatric disorders. The outcome of cognitive impairment in Alzheimer's disease has both individual (the patients and their families) and socio-economic effects. The prevalence of Alzheimer's disease doubles after the age of 65 years, every 4.5 years. An etiologically heterogenic group of disorders related to aging as well as genetic and environmental interactions probably underlie the impairment in Alzheimer's disease. Those factors cause the degeneration of brain tissue which leads to significant cognitive dysfunction. There are two main hypotheses that are linked to the process of neurodegeneration: (i) amyloid cascade and (ii) the role of secretases and dysfunction of mitochondria. From the therapeutic standpoint it is crucial to get an early diagnosis and start with an adequate treatment. The undeniable progress in the field of biomarker research should lead to a better understanding of the early stages of the disorder. So far, the best recognised and described biomarkers of Alzheimer's disease, which can be detected in both cerebrospinal fluid and blood, are: beta-amyloid, tau-protein and phosphorylated tau-protein (phospho-tau). The article discusses the usefulness of the known biomarkers of Alzheimer's disease in early diagnosis.

  4. Cancer genomics

    DEFF Research Database (Denmark)

    Norrild, Bodil; Guldberg, Per; Ralfkiær, Elisabeth Methner

    2007-01-01

    Almost all cells in the human body contain a complete copy of the genome with an estimated number of 25,000 genes. The sequences of these genes make up about three percent of the genome and comprise the inherited set of genetic information. The genome also contains information that determines whe...

  5. Biomarkers in cancer screening: a public health perspective.

    Science.gov (United States)

    Srivastava, Sudhir; Gopal-Srivastava, Rashmi

    2002-08-01

    The last three decades have witnessed a rapid advancement and diffusion of technology in health services. Technological innovations have given health service providers the means to diagnose and treat an increasing number of illnesses, including cancer. In this effort, research on biomarkers for cancer detection and risk assessment has taken a center stage in our effort to reduce cancer deaths. For the first time, scientists have the technologies to decipher and understand these biomarkers and to apply them to earlier cancer detection. By identifying people at high risk of developing cancer, it would be possible to develop intervention efforts on prevention rather than treatment. Once fully developed and validated, then the regular clinical use of biomarkers in early detection and risk assessment will meet nationally recognized health care needs: detection of cancer at its earliest stage. The dramatic rise in health care costs in the past three decades is partly related to the proliferation of new technologies. More recent analysis indicates that technological change, such as new procedures, products and capabilities, is the primary explanation of the historical increase in expenditure. Biomarkers are the new entrants in this competing environment. Biomarkers are considered as a competing, halfway or add-on technology. Technology such as laboratory tests of biomarkers will cost less compared with computed tomography (CT) scans and other radiographs. However, biomarkers for earlier detection and risk assessment have not achieved the level of confidence required for clinical applications. This paper discusses some issues related to biomarker development, validation and quality assurance. Some data on the trends of diagnostic technologies, proteomics and genomics are presented and discussed in terms of the market share. Eventually, the use of biomarkers in health care could reduce cost by providing noninvasive, sensitive and reliable assays at a fraction of the cost of

  6. Biomarkers in Diabetic Retinopathy

    Science.gov (United States)

    Jenkins, Alicia J.; Joglekar, Mugdha V.; Hardikar, Anandwardhan A.; Keech, Anthony C.; O'Neal, David N.; Januszewski, Andrzej S.

    2015-01-01

    There is a global diabetes epidemic correlating with an increase in obesity. This coincidence may lead to a rise in the prevalence of type 2 diabetes. There is also an as yet unexplained increase in the incidence of type 1 diabetes, which is not related to adiposity. Whilst improved diabetes care has substantially improved diabetes outcomes, the disease remains a common cause of working age adult-onset blindness. Diabetic retinopathy is the most frequently occurring complication of diabetes; it is greatly feared by many diabetes patients. There are multiple risk factors and markers for the onset and progression of diabetic retinopathy, yet residual risk remains. Screening for diabetic retinopathy is recommended to facilitate early detection and treatment. Common biomarkers of diabetic retinopathy and its risk in clinical practice today relate to the visualization of the retinal vasculature and measures of glycemia, lipids, blood pressure, body weight, smoking, and pregnancy status. Greater knowledge of novel biomarkers and mediators of diabetic retinopathy, such as those related to inflammation and angiogenesis, has contributed to the development of additional therapeutics, in particular for late-stage retinopathy, including intra-ocular corticosteroids and intravitreal vascular endothelial growth factor inhibitors ('anti-VEGFs') agents. Unfortunately, in spite of a range of treatments (including laser photocoagulation, intraocular steroids, and anti-VEGF agents, and more recently oral fenofibrate, a PPAR-alpha agonist lipid-lowering drug), many patients with diabetic retinopathy do not respond well to current therapeutics. Therefore, more effective treatments for diabetic retinopathy are necessary. New analytical techniques, in particular those related to molecular markers, are accelerating progress in diabetic retinopathy research. Given the increasing incidence and prevalence of diabetes, and the limited capacity of healthcare systems to screen and treat

  7. Biomarkers in Diabetic Retinopathy.

    Science.gov (United States)

    Jenkins, Alicia J; Joglekar, Mugdha V; Hardikar, Anandwardhan A; Keech, Anthony C; O'Neal, David N; Januszewski, Andrzej S

    2015-01-01

    There is a global diabetes epidemic correlating with an increase in obesity. This coincidence may lead to a rise in the prevalence of type 2 diabetes. There is also an as yet unexplained increase in the incidence of type 1 diabetes, which is not related to adiposity. Whilst improved diabetes care has substantially improved diabetes outcomes, the disease remains a common cause of working age adult-onset blindness. Diabetic retinopathy is the most frequently occurring complication of diabetes; it is greatly feared by many diabetes patients. There are multiple risk factors and markers for the onset and progression of diabetic retinopathy, yet residual risk remains. Screening for diabetic retinopathy is recommended to facilitate early detection and treatment. Common biomarkers of diabetic retinopathy and its risk in clinical practice today relate to the visualization of the retinal vasculature and measures of glycemia, lipids, blood pressure, body weight, smoking, and pregnancy status. Greater knowledge of novel biomarkers and mediators of diabetic retinopathy, such as those related to inflammation and angiogenesis, has contributed to the development of additional therapeutics, in particular for late-stage retinopathy, including intra-ocular corticosteroids and intravitreal vascular endothelial growth factor inhibitors ('anti-VEGFs') agents. Unfortunately, in spite of a range of treatments (including laser photocoagulation, intraocular steroids, and anti-VEGF agents, and more recently oral fenofibrate, a PPAR-alpha agonist lipid-lowering drug), many patients with diabetic retinopathy do not respond well to current therapeutics. Therefore, more effective treatments for diabetic retinopathy are necessary. New analytical techniques, in particular those related to molecular markers, are accelerating progress in diabetic retinopathy research. Given the increasing incidence and prevalence of diabetes, and the limited capacity of healthcare systems to screen and treat

  8. Applications of Support Vector Machine (SVM) Learning in Cancer Genomics

    OpenAIRE

    HUANG, SHUJUN; CAI, NIANGUANG; PACHECO, PEDRO PENZUTI; NARANDES, SHAVIRA; WANG, YANG; XU, WAYNE

    2017-01-01

    Machine learning with maximization (support) of separating margin (vector), called support vector machine (SVM) learning, is a powerful classification tool that has been used for cancer genomic classification or subtyping. Today, as advancements in high-throughput technologies lead to production of large amounts of genomic and epigenomic data, the classification feature of SVMs is expanding its use in cancer genomics, leading to the discovery of new biomarkers, new drug targets, and a better ...

  9. Biomarkers for personalized oncology: recent advances and future challenges.

    Science.gov (United States)

    Kalia, Madhu

    2015-03-01

    Cancer is a group of diseases characterized by the uncontrolled growth and spread of abnormal cells and oncology is a branch of medicine that deals with tumors. The last decade has seen significant advances in the development of biomarkers in oncology that play a critical role in understanding molecular and cellular mechanisms which drive tumor initiation, maintenance and progression. Clinical molecular diagnostics and biomarker discoveries in oncology are advancing rapidly as we begin to understand the complex mechanisms that transform a normal cell into an abnormal one. These discoveries have fueled the development of novel drug targets and new treatment strategies. The standard of care for patients with advanced-stage cancers has shifted away from an empirical treatment strategy based on the clinical-pathological profile to one where a biomarker driven treatment algorithm based on the molecular profile of the tumor is used. Recent advances in multiplex genotyping technologies and high-throughput genomic profiling by next-generation sequencing make possible the rapid and comprehensive analysis of the cancer genome of individual patients even from very little tumor biopsy material. Predictive (diagnostic) biomarkers are helpful in matching targeted therapies with patients and in preventing toxicity of standard (systemic) therapies. Prognostic biomarkers identify somatic germ line mutations, changes in DNA methylation, elevated levels of microRNA (miRNA) and circulating tumor cells (CTC) in blood. Predictive biomarkers using molecular diagnostics are currently in use in clinical practice of personalized oncotherapy for the treatment of five diseases: chronic myeloid leukemia, colon, breast, lung cancer and melanoma and these biomarkers are being used successfully to evaluate benefits that can be achieved through targeted therapy. Examples of these molecularly targeted biomarker therapies are: tyrosine kinase inhibitors in chronic myeloid leukemia and

  10. Predictive Biomarkers for Asthma Therapy.

    Science.gov (United States)

    Medrek, Sarah K; Parulekar, Amit D; Hanania, Nicola A

    2017-09-19

    Asthma is a heterogeneous disease characterized by multiple phenotypes. Treatment of patients with severe disease can be challenging. Predictive biomarkers are measurable characteristics that reflect the underlying pathophysiology of asthma and can identify patients that are likely to respond to a given therapy. This review discusses current knowledge regarding predictive biomarkers in asthma. Recent trials evaluating biologic therapies targeting IgE, IL-5, IL-13, and IL-4 have utilized predictive biomarkers to identify patients who might benefit from treatment. Other work has suggested that using composite biomarkers may offer enhanced predictive capabilities in tailoring asthma therapy. Multiple biomarkers including sputum eosinophil count, blood eosinophil count, fractional concentration of nitric oxide in exhaled breath (FeNO), and serum periostin have been used to identify which patients will respond to targeted asthma medications. Further work is needed to integrate predictive biomarkers into clinical practice.

  11. Value-based genomics.

    Science.gov (United States)

    Gong, Jun; Pan, Kathy; Fakih, Marwan; Pal, Sumanta; Salgia, Ravi

    2018-03-20

    Advancements in next-generation sequencing have greatly enhanced the development of biomarker-driven cancer therapies. The affordability and availability of next-generation sequencers have allowed for the commercialization of next-generation sequencing platforms that have found widespread use for clinical-decision making and research purposes. Despite the greater availability of tumor molecular profiling by next-generation sequencing at our doorsteps, the achievement of value-based care, or improving patient outcomes while reducing overall costs or risks, in the era of precision oncology remains a looming challenge. In this review, we highlight available data through a pre-established and conceptualized framework for evaluating value-based medicine to assess the cost (efficiency), clinical benefit (effectiveness), and toxicity (safety) of genomic profiling in cancer care. We also provide perspectives on future directions of next-generation sequencing from targeted panels to whole-exome or whole-genome sequencing and describe potential strategies needed to attain value-based genomics.

  12. Biomarkers in Prostate Cancer Epidemiology

    Directory of Open Access Journals (Sweden)

    Mudit Verma

    2011-09-01

    Full Text Available Understanding the etiology of a disease such as prostate cancer may help in identifying populations at high risk, timely intervention of the disease, and proper treatment. Biomarkers, along with exposure history and clinical data, are useful tools to achieve these goals. Individual risk and population incidence of prostate cancer result from the intervention of genetic susceptibility and exposure. Biochemical, epigenetic, genetic, and imaging biomarkers are used to identify people at high risk for developing prostate cancer. In cancer epidemiology, epigenetic biomarkers offer advantages over other types of biomarkers because they are expressed against a person’s genetic background and environmental exposure, and because abnormal events occur early in cancer development, which includes several epigenetic alterations in cancer cells. This article describes different biomarkers that have potential use in studying the epidemiology of prostate cancer. We also discuss the characteristics of an ideal biomarker for prostate cancer, and technologies utilized for biomarker assays. Among epigenetic biomarkers, most reports indicate GSTP1 hypermethylation as the diagnostic marker for prostate cancer; however, NKX2-5, CLSTN1, SPOCK2, SLC16A12, DPYS, and NSE1 also have been reported to be regulated by methylation mechanisms in prostate cancer. Current challenges in utilization of biomarkers in prostate cancer diagnosis and epidemiologic studies and potential solutions also are discussed.

  13. Biomarker Identification Using Text Mining

    Directory of Open Access Journals (Sweden)

    Hui Li

    2012-01-01

    Full Text Available Identifying molecular biomarkers has become one of the important tasks for scientists to assess the different phenotypic states of cells or organisms correlated to the genotypes of diseases from large-scale biological data. In this paper, we proposed a text-mining-based method to discover biomarkers from PubMed. First, we construct a database based on a dictionary, and then we used a finite state machine to identify the biomarkers. Our method of text mining provides a highly reliable approach to discover the biomarkers in the PubMed database.

  14. Chiral Biomarkers in Meteorites

    Science.gov (United States)

    Hoover, Richard B.

    2010-01-01

    The chirality of organic molecules with the asymmetric location of group radicals was discovered in 1848 by Louis Pasteur during his investigations of the rotation of the plane of polarization of light by crystals of sodium ammonium paratartrate. It is well established that the amino acids in proteins are exclusively Levorotary (L-aminos) and the sugars in DNA and RNA are Dextrorotary (D-sugars). This phenomenon of homochirality of biological polymers is a fundamental property of all life known on Earth. Furthermore, abiotic production mechanisms typically yield recemic mixtures (i.e. equal amounts of the two enantiomers). When amino acids were first detected in carbonaceous meteorites, it was concluded that they were racemates. This conclusion was taken as evidence that they were extraterrestrial and produced by abiologically. Subsequent studies by numerous researchers have revealed that many of the amino acids in carbonaceous meteorites exhibit a significant L-excess. The observed chirality is much greater than that produced by any currently known abiotic processes (e.g. Linearly polarized light from neutron stars; Circularly polarized ultraviolet light from faint stars; optically active quartz powders; inclusion polymerization in clay minerals; Vester-Ulbricht hypothesis of parity violations, etc.). This paper compares the measured chirality detected in the amino acids of carbonaceous meteorites with the effect of these diverse abiotic processes. IT is concluded that the levels observed are inconsistent with post-arrival biological contamination or with any of the currently known abiotic production mechanisms. However, they are consistent with ancient biological processes on the meteorite parent body. This paper will consider these chiral biomarkers in view of the detection of possible microfossils found in the Orgueil and Murchison carbonaceous meteorites. Energy dispersive x-ray spectroscopy (EDS) data obtained on these morphological biomarkers will be

  15. Hepcidin- A Burgeoning Biomarker

    Directory of Open Access Journals (Sweden)

    Hemkant Manikrao Deshmukh

    2017-10-01

    Full Text Available The discovery of hepcidin has triggered a virtual ignition of studies on iron metabolism and related disorders. The peptide hormone hepcidin is a key homeostatic regulator of iron metabolism. The synthesis of hepcidin is induced by systemic iron levels and by inflammatory stimuli. Several human diseases are associated with variations in hepcidin concentrations. The evaluation of hepcidin in biological fluids is therefore a promising device in the diagnosis and management of medical situations in which iron metabolism is affected. Thus, it made us to recapitulate role of hepcidin as biomarker.

  16. Towards Improved Biomarker Research

    DEFF Research Database (Denmark)

    Kjeldahl, Karin

    This thesis takes a look at the data analytical challenges associated with the search for biomarkers in large-scale biological data such as transcriptomics, proteomics and metabolomics data. These studies aim to identify genes, proteins or metabolites which can be associated with e.g. a diet...... with very specific competencies. In order to optimize the basis of a sound and fruitful data analysis, suggestions are givenwhich focus on (1) collection of good data, (2) preparation of data for the data analysis and (3) a sound data analysis. If these steps are optimized, PLS is a also a very goodmethod...

  17. Identification of aberrant gene expression associated with aberrant promoter methylation in primordial germ cells between E13 and E16 rat F3 generation vinclozolin lineage.

    Science.gov (United States)

    Taguchi, Y-h

    2015-01-01

    Transgenerational epigenetics (TGE) are currently considered important in disease, but the mechanisms involved are not yet fully understood. TGE abnormalities expected to cause disease are likely to be initiated during development and to be mediated by aberrant gene expression associated with aberrant promoter methylation that is heritable between generations. However, because methylation is removed and then re-established during development, it is not easy to identify promoter methylation abnormalities by comparing normal lineages with those expected to exhibit TGE abnormalities. This study applied the recently proposed principal component analysis (PCA)-based unsupervised feature extraction to previously reported and publically available gene expression/promoter methylation profiles of rat primordial germ cells, between E13 and E16 of the F3 generation vinclozolin lineage that are expected to exhibit TGE abnormalities, to identify multiple genes that exhibited aberrant gene expression/promoter methylation during development. The biological feasibility of the identified genes were tested via enrichment analyses of various biological concepts including pathway analysis, gene ontology terms and protein-protein interactions. All validations suggested superiority of the proposed method over three conventional and popular supervised methods that employed t test, limma and significance analysis of microarrays, respectively. The identified genes were globally related to tumors, the prostate, kidney, testis and the immune system and were previously reported to be related to various diseases caused by TGE. Among the genes reported by PCA-based unsupervised feature extraction, we propose that chemokine signaling pathways and leucine rich repeat proteins are key factors that initiate transgenerational epigenetic-mediated diseases, because multiple genes included in these two categories were identified in this study.

  18. What is a biomarker? Research investments and lack of clinical integration necessitate a review of biomarker terminology and validation schema.

    Science.gov (United States)

    Ptolemy, Adam S; Rifai, Nader

    2010-01-01

    A continual trend of annual growth can be seen within research devoted to the discovery and validation of disease biomarkers within both the natural and clinical sciences. This expansion of intellectual endeavours was quantified through database searches of (a) research grant awards provided by the various branches of the National Institutes of Health (NIH) and (b) academic publications. A search of awards presented between 1986 and 2009 revealed a total of 28,856 grants awarded by the NIH containing the term "biomarker". The total funds for these awards in 2008 and 2009 alone were over $2.5 billion. During the same respective time frames, searches of "biomarker" and either "discovery", "genomics", "proteomics" or "metabolomics" yielded a total of 4,928 NIH grants whose combined funding exceeded $1.2 billion. The derived trend in NIH awards paralleled the annual expansion in "biomarker" literature. A PubMed search for the term, between 1990 and 2009, revealed a total of 441,510 published articles, with 38,457 published in 2008. These enormous investments and academic outputs however have not translated into the expected integration of new biomarkers for patient care. For example no proteomics derived biomarkers are currently being utilized in routine clinical management. This translational chasm necessitates a review of the previously proposed biomarker definitions and evaluation schema. A subsequent discussion of both the analytical and pre-analytical considerations for such research is also presented within. This required knowledge should aid scientists in their pursuit and validation of new biological markers of disease.

  19. Biomarkers in Vasculitis

    Science.gov (United States)

    Monach, Paul A.

    2014-01-01

    Purpose of review Better biomarkers are needed for guiding management of patients with vasculitis. Large cohorts and technological advances had led to an increase in pre-clinical studies of potential biomarkers. Recent findings The most interesting markers described recently include a gene expression signature in CD8+ T cells that predicts tendency to relapse or remain relapse-free in ANCA-associated vasculitis, and a pair of urinary proteins that are elevated in Kawasaki disease but not other febrile illnesses. Both of these studies used “omics” technologies to generate and then test hypotheses. More conventional hypothesis-based studies have indicated that the following circulating proteins have potential to improve upon clinically available tests: pentraxin-3 in giant cell arteritis and Takayasu’s arteritis; von Willebrand factor antigen in childhood central nervous system vasculitis; eotaxin-3 and other markers related to eosinophils or Th2 immune responses in eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome); and MMP-3, TIMP-1, and CXCL13 in ANCA-associated vasculitis. Summary New markers testable in blood and urine have the potential to assist with diagnosis, staging, assessment of current disease activity, and prognosis. However, the standards for clinical usefulness, in particular the demonstration of either very high sensitivity or very high specificity, have yet to be met for clinically relevant outcomes. PMID:24257367

  20. Genome Imprinting

    Indian Academy of Sciences (India)

    the cell nucleus (mitochondrial and chloroplast genomes), and. (3) traits governed ... tively good embryonic development but very poor development of membranes and ... Human homologies for the type of situation described above are naturally ..... imprint; (b) New modifications of the paternal genome in germ cells of each ...

  1. Baculovirus Genomics

    NARCIS (Netherlands)

    Oers, van M.M.; Vlak, J.M.

    2007-01-01

    Baculovirus genomes are covalently closed circles of double stranded-DNA varying in size between 80 and 180 kilobase-pair. The genomes of more than fourty-one baculoviruses have been sequenced to date. The majority of these (37) are pathogenic to lepidopteran hosts; three infect sawflies

  2. Genomic Testing

    Science.gov (United States)

    ... this database. Top of Page Evaluation of Genomic Applications in Practice and Prevention (EGAPP™) In 2004, the Centers for Disease Control and Prevention launched the EGAPP initiative to establish and test a ... and other applications of genomic technology that are in transition from ...

  3. Ancient genomes

    OpenAIRE

    Hoelzel, A Rus

    2005-01-01

    Ever since its invention, the polymerase chain reaction has been the method of choice for work with ancient DNA. In an application of modern genomic methods to material from the Pleistocene, a recent study has instead undertaken to clone and sequence a portion of the ancient genome of the cave bear.

  4. [Autoantibodies as biomarkers].

    Science.gov (United States)

    Tron, François

    2014-01-01

    Activation and differentiation of autoreactive B-lymphocytes lead to the production of autoantibodies, which are thus the direct consequence of the autoimmune process. They often constitute biomarkers of autoimmune diseases and are measured by tests displaying various diagnosis sensitivity and specificity. Autoantibody titers can be correlated to the disease activity and certain autoantibody populations associated with particular clinical manifestations or tissue lesions. The demonstration that autoantibodies appear years before the onset of autoimmune diseases indicates that their presence in healthy individuals may be a predictive marker of the occurrence of disease. Certain autoantibodies could also be predictive markers of a therapeutic response to biologics and of the occurrence of side effects as well. Thus, autoantibodies are useful tools in the diagnosis and the management of patients with organ specific or non-organ specific autoimmune diseases at different steps of the autoimmune process. Copyright © 2013. Published by Elsevier Masson SAS.

  5. New biomarkers for sepsis

    Directory of Open Access Journals (Sweden)

    Li-xin XIE

    2013-01-01

    Full Text Available There is a higher sepsis rate in the intensive care unit (ICU patients, which is one of the most important causes for patient death, but the sepsis lacks specific clinical manifestations. Exploring sensitive and specific molecular markers for infection that accurately reflect infection severity and prognosis is very clinically important. In this article, based on our previous study, we introduce some new biomarkers with high sensitivity and specificity for the diagnosis and predicting the prognosis and severity of sepsis. Increase of serum soluble(s triggering receptor expressed on myeloid cells-1 (sTREM-1 suggests a poor prognosis of septic patients, and changes of locus rs2234237 of sTREM-1 may be the one of important mechanisms. Additionally, urine sTREM-1 can provide an early warning of possible secondary acute kidney injury (AKI in sepsis patients. Serum sCD163 level was found to be a more important factor than procalcitonin (PCT and C-reactive protein (CRP in prognosis of sepsis, especially severe sepsis. Moreover, urine sCD163 also shows excellent performance in the diagnosis of sepsis and sepsis-associated AKI. Circulating microRNAs, such as miR-150, miR-297, miR-574-5p, miR -146a , miR-223, miR -15a and miR-16, also play important roles in the evaluation of status of septic patients. In the foreseeable future, newly-emerging technologies, including proteomics, metabonomics and trans-omics, may exert profound effects on the discovery of valuable biomarkers for sepsis.

  6. Multiple Sclerosis Cerebrospinal Fluid Biomarkers

    Directory of Open Access Journals (Sweden)

    Gavin Giovannoni

    2006-01-01

    Full Text Available Cerebrospinal fluid (CSF is the body fluid closest to the pathology of multiple sclerosis (MS. For many candidate biomarkers CSF is the only fluid that can be investigated. Several factors need to be standardized when sampling CSF for biomarker research: time/volume of CSF collection, sample processing/storage, and the temporal relationship of sampling to clinical or MRI markers of disease activity. Assays used for biomarker detection must be validated so as to optimize the power of the studies. A formal method for establishing whether or not a particular biomarker can be used as a surrogate end-point needs to be adopted. This process is similar to that used in clinical trials, where the reporting of studies has to be done in a standardized way with sufficient detail to permit a critical review of the study and to enable others to reproduce the study design. A commitment must be made to report negative studies so as to prevent publication bias. Pre-defined consensus criteria need to be developed for MS-related prognostic biomarkers. Currently no candidate biomarker is suitable as a surrogate end-point. Bulk biomarkers of the neurodegenerative process such as glial fibrillary acidic protein (GFAP and neurofilaments (NF have advantages over intermittent inflammatory markers.

  7. Biomarkers for Detecting Mitochondrial Disorders

    Directory of Open Access Journals (Sweden)

    Josef Finsterer

    2018-01-01

    Full Text Available (1 Objectives: Mitochondrial disorders (MIDs are a genetically and phenotypically heterogeneous group of slowly or rapidly progressive disorders with onset from birth to senescence. Because of their variegated clinical presentation, MIDs are difficult to diagnose and are frequently missed in their early and late stages. This is why there is a need to provide biomarkers, which can be easily obtained in the case of suspecting a MID to initiate the further diagnostic work-up. (2 Methods: Literature review. (3 Results: Biomarkers for diagnostic purposes are used to confirm a suspected diagnosis and to facilitate and speed up the diagnostic work-up. For diagnosing MIDs, a number of dry and wet biomarkers have been proposed. Dry biomarkers for MIDs include the history and clinical neurological exam and structural and functional imaging studies of the brain, muscle, or myocardium by ultrasound, computed tomography (CT, magnetic resonance imaging (MRI, MR-spectroscopy (MRS, positron emission tomography (PET, or functional MRI. Wet biomarkers from blood, urine, saliva, or cerebrospinal fluid (CSF for diagnosing MIDs include lactate, creatine-kinase, pyruvate, organic acids, amino acids, carnitines, oxidative stress markers, and circulating cytokines. The role of microRNAs, cutaneous respirometry, biopsy, exercise tests, and small molecule reporters as possible biomarkers is unsolved. (4 Conclusions: The disadvantages of most putative biomarkers for MIDs are that they hardly meet the criteria for being acceptable as a biomarker (missing longitudinal studies, not validated, not easily feasible, not cheap, not ubiquitously available and that not all MIDs manifest in the brain, muscle, or myocardium. There is currently a lack of validated biomarkers for diagnosing MIDs.

  8. Genomic biomarkers and clinical outcomes of physical activity.

    Science.gov (United States)

    Izzotti, Alberto

    2011-07-01

    Clinical and experimental studies in humans provide evidence that moderate physical activity significantly decreases artery oxidative damage to nuclear DNA, DNA-adducts related to age and dyslipedemia, and mitochondrial DNA damage. Maintenance of adequate mitochondrial function is crucial for preventing lipid accumulation and peroxidation occurring in atherosclerosis. Studies performed on human muscle biopsies analyzing gene expression in living humans reveal that physically active subjects improve the expression of genes involved in mitochondrial function and of related microRNAs. The attenuation of oxidative damage to nuclear and mitochondrial DNA by physical activity resulted in beneficial effects due to polymorphisms of glutathione S-transferases genes. Subjects bearing null GSTM1/T1 polymorphisms have poor life expectancy in the case of being sedentary, which was increased 2.6-fold in case they performed physical activity. These findings indicate that the preventive effect of physical activity undergoes interindividual variation affected by genetic polymorphisms. © 2011 New York Academy of Sciences.

  9. Aberrantly methylated DNA as a biomarker in breast cancer.

    Science.gov (United States)

    Kristiansen, Søren; Jørgensen, Lars M; Guldberg, Per; Sölétormos, György

    2013-01-01

    Aberrant DNA hypermethylation at gene promoters is a frequent event in human breast cancer. Recent genome-wide studies have identified hundreds of genes that exhibit differential methylation between breast cancer cells and normal breast tissue. Due to the tumor-specific nature of DNA hypermethylation events, their use as tumor biomarkers is usually not hampered by analytical signals from normal cells, which is a general problem for existing protein tumor markers used for clinical assessment of breast cancer. There is accumulating evidence that DNA-methylation changes in breast cancer patients occur early during tumorigenesis. This may open up for effective screening, and analysis of blood or nipple aspirate may later help in diagnosing breast cancer. As a more detailed molecular characterization of different types of breast cancer becomes available, the ability to divide patients into subgroups based on DNA biomarkers may improve prognosis. Serial monitoring of DNA-methylation markers in blood during treatment may be useful, particularly when the cancer burden is below the detection level for standard imaging techniques. Overall, aberrant DNA methylation has a great potential as a versatile biomarker tool for screening, diagnosis, prognosis and monitoring of breast cancer. Standardization of methods and biomarker panels will be required to fully exploit this clinical potential.

  10. Urinary Biomarkers of Brain Diseases

    Directory of Open Access Journals (Sweden)

    Manxia An

    2015-12-01

    Full Text Available Biomarkers are the measurable changes associated with a physiological or pathophysiological process. Unlike blood, urine is not subject to homeostatic mechanisms. Therefore, greater fluctuations could occur in urine than in blood, better reflecting the changes in human body. The roadmap of urine biomarker era was proposed. Although urine analysis has been attempted for clinical diagnosis, and urine has been monitored during the progression of many diseases, particularly urinary system diseases, whether urine can reflect brain disease status remains uncertain. As some biomarkers of brain diseases can be detected in the body fluids such as cerebrospinal fluid and blood, there is a possibility that urine also contain biomarkers of brain diseases. This review summarizes the clues of brain diseases reflected in the urine proteome and metabolome.

  11. Biomarkers of latent TB infection

    DEFF Research Database (Denmark)

    Ruhwald, Morten; Ravn, Pernille

    2009-01-01

    For the last 100 years, the tuberculin skin test (TST) has been the only diagnostic tool available for latent TB infection (LTBI) and no biomarker per se is available to diagnose the presence of LTBI. With the introduction of M. tuberculosis-specific IFN-gamma release assays (IGRAs), a new area...... of in vitro immunodiagnostic tests for LTBI based on biomarker readout has become a reality. In this review, we discuss existing evidence on the clinical usefulness of IGRAs and the indefinite number of potential new biomarkers that can be used to improve diagnosis of latent TB infection. We also present...... early data suggesting that the monocyte-derived chemokine inducible protein-10 may be useful as a novel biomarker for the immunodiagnosis of latent TB infection....

  12. Herbarium genomics

    DEFF Research Database (Denmark)

    Bakker, Freek T.; Lei, Di; Yu, Jiaying

    2016-01-01

    Herbarium genomics is proving promising as next-generation sequencing approaches are well suited to deal with the usually fragmented nature of archival DNA. We show that routine assembly of partial plastome sequences from herbarium specimens is feasible, from total DNA extracts and with specimens...... up to 146 years old. We use genome skimming and an automated assembly pipeline, Iterative Organelle Genome Assembly, that assembles paired-end reads into a series of candidate assemblies, the best one of which is selected based on likelihood estimation. We used 93 specimens from 12 different...... correlation between plastome coverage and nuclear genome size (C value) in our samples, but the range of C values included is limited. Finally, we conclude that routine plastome sequencing from herbarium specimens is feasible and cost-effective (compared with Sanger sequencing or plastome...

  13. Breath biomarkers in toxicology.

    Science.gov (United States)

    Pleil, Joachim D

    2016-11-01

    Exhaled breath has joined blood and urine as a valuable resource for sampling and analyzing biomarkers in human media for assessing exposure, uptake metabolism, and elimination of toxic chemicals. This article focuses current use of exhaled gas, aerosols, and vapor in human breath, the methods for collection, and ultimately the use of the resulting data. Some advantages of breath are the noninvasive and self-administered nature of collection, the essentially inexhaustible supply, and that breath sampling does not produce potentially infectious waste such as needles, wipes, bandages, and glassware. In contrast to blood and urine, breath samples can be collected on demand in rapid succession and so allow toxicokinetic observations of uptake and elimination in any time frame. Furthermore, new technologies now allow capturing condensed breath vapor directly, or just the aerosol fraction alone, to gain access to inorganic species, lung pH, proteins and protein fragments, cellular DNA, and whole microorganisms from the pulmonary microbiome. Future applications are discussed, especially the use of isotopically labeled probes, non-targeted (discovery) analysis, cellular level toxicity testing, and ultimately assessing "crowd breath" of groups of people and the relation to dose of airborne and other environmental chemicals at the population level.

  14. Analysis of biomarker data a practical guide

    CERN Document Server

    Looney, Stephen W

    2015-01-01

    A "how to" guide for applying statistical methods to biomarker data analysis Presenting a solid foundation for the statistical methods that are used to analyze biomarker data, Analysis of Biomarker Data: A Practical Guide features preferred techniques for biomarker validation. The authors provide descriptions of select elementary statistical methods that are traditionally used to analyze biomarker data with a focus on the proper application of each method, including necessary assumptions, software recommendations, and proper interpretation of computer output. In addition, the book discusses

  15. The future: biomarkers, biosensors, neuroinformatics, and e-neuropsychiatry.

    Science.gov (United States)

    Lowe, Christopher R

    2011-01-01

    The emergence of molecular biomarkers for psychological, psychiatric, and neurodegenerative disorders is beginning to change current diagnostic paradigms for this debilitating family of mental illnesses. The development of new genomic, proteomic, and metabolomic tools has created the prospect of sensitive and specific biochemical tests to replace traditional pen-and-paper questionnaires. In the future, the realization of biosensor technologies, point-of-care testing, and the fusion of clinical biomarker data, electroencephalogram, and MRI data with the patient's past medical history, biopatterns, and prognosis may create personalized bioprofiles or fingerprints for brain disorders. Further, the application of mobile communications technology and grid computing to support data-, computation- and knowledge-based tasks will assist disease prediction, diagnosis, prognosis, and compliance monitoring. It is anticipated that, ultimately, mobile devices could become the next generation of personalized pharmacies. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Secure searching of biomarkers through hybrid homomorphic encryption scheme.

    Science.gov (United States)

    Kim, Miran; Song, Yongsoo; Cheon, Jung Hee

    2017-07-26

    As genome sequencing technology develops rapidly, there has lately been an increasing need to keep genomic data secure even when stored in the cloud and still used for research. We are interested in designing a protocol for the secure outsourcing matching problem on encrypted data. We propose an efficient method to securely search a matching position with the query data and extract some information at the position. After decryption, only a small amount of comparisons with the query information should be performed in plaintext state. We apply this method to find a set of biomarkers in encrypted genomes. The important feature of our method is to encode a genomic database as a single element of polynomial ring. Since our method requires a single homomorphic multiplication of hybrid scheme for query computation, it has the advantage over the previous methods in parameter size, computation complexity, and communication cost. In particular, the extraction procedure not only prevents leakage of database information that has not been queried by user but also reduces the communication cost by half. We evaluate the performance of our method and verify that the computation on large-scale personal data can be securely and practically outsourced to a cloud environment during data analysis. It takes about 3.9 s to search-and-extract the reference and alternate sequences at the queried position in a database of size 4M. Our solution for finding a set of biomarkers in DNA sequences shows the progress of cryptographic techniques in terms of their capability can support real-world genome data analysis in a cloud environment.

  17. DNA Methylation as a Biomarker for Preeclampsia

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Cindy M.; Ralph, Jody L.; Wright, Michelle L.; Linggi, Bryan E.; Ohm, Joyce E.

    2014-10-01

    Background: Preeclampsia contributes significantly to pregnancy-associated morbidity and mortality as well as future risk of cardiovascular disease in mother and offspring, and preeclampsia in offspring. The lack of reliable methods for early detection limits the opportunities for prevention, diagnosis, and timely treatment. Purpose: The purpose of this study was to explore distinct DNA methylation patterns associated with preeclampsia in both maternal cells and fetal-derived tissue that represent potential biomarkers to predict future preeclampsia and inheritance in children. Method: A convenience sample of nulliparous women (N = 55) in the first trimester of pregnancy was recruited for this prospective study. Genome-wide DNA methylation was quantified in first-trimester maternal peripheral white blood cells and placental chorionic tissue from normotensive women and those with preeclampsia (n = 6/group). Results: Late-onset preeclampsia developed in 12.7% of women. Significant differences in DNA methylation were identified in 207 individual linked cytosine and guanine (CpG) sites in maternal white blood cells collected in the first trimester (132 sites with gain and 75 sites with loss of methylation), which were common to approximately 75% of the differentially methylated CpG sites identified in chorionic tissue of fetal origin. Conclusion: This study is the first to identify maternal epigenetic targets and common targets in fetal-derived tissue that represent putative biomarkers for early detection and heritable risk of preeclampsia. Findings may pave the way for diagnosis of preeclampsia prior to its clinical presentation and acute damaging effects, and the potential for prevention of the detrimental long-term sequelae.

  18. Synthesis of eukaryotic lipid biomarkers in the bacterial domain

    Science.gov (United States)

    Welander, P. V.; Banta, A. B.; Lee, A. K.; Wei, J. H.

    2017-12-01

    Lipid biomarkers are organic molecules preserved in sediments and sedimentary rocks that can function as geological proxies for certain microbial taxa or for specific environmental conditions. These molecular fossils provide a link between organisms and their environments in both modern and ancient settings and have afforded significant insight into ancient climatic events, mass extinctions, and various evolutionary transitions throughout Earth's history. However, the proper interpretation of lipid biomarkers is dependent on a broad understanding of their diagenetic precursors in modern systems. This includes understanding the taphonomic transformations that these molecules undergo, their biosynthetic pathways, and the ecological conditions that affect their cellular production. In this study, we focus on one group of lipid biomarkers - the sterols. These are polycyclic isoprenoidal lipids that have a high preservation potential and play a critical role in the physiology of most eukaryotes. However, the synthesis and function of these lipids in the bacterial domain has not been fully explored. Here we utilize a combination of bioinformatics, microbial genetics, and biochemistry to demonstrate that bacterial sterol producers are more prevalent in environmental metagenomic samples than in the genomic databases of cultured organisms and to identify novel proteins required to synthesize and modify sterols in bacteria. These proteins represent a distinct pathway for sterol synthesis exclusive to bacteria and indicate that sterol synthesis in bacteria may have evolved independently of eukaryotic sterol biosynthesis. Taken together, these results demonstrate how studies in extant bacteria can provide insight into the biological sources and the biosynthetic pathways of specific lipid biomarkers and in turn may allow for more robust interpretation of biomarker signatures.

  19. Personalized Cancer Medicine: Molecular Diagnostics, Predictive biomarkers, and Drug Resistance

    Science.gov (United States)

    Gonzalez de Castro, D; Clarke, P A; Al-Lazikani, B; Workman, P

    2013-01-01

    The progressive elucidation of the molecular pathogenesis of cancer has fueled the rational development of targeted drugs for patient populations stratified by genetic characteristics. Here we discuss general challenges relating to molecular diagnostics and describe predictive biomarkers for personalized cancer medicine. We also highlight resistance mechanisms for epidermal growth factor receptor (EGFR) kinase inhibitors in lung cancer. We envisage a future requiring the use of longitudinal genome sequencing and other omics technologies alongside combinatorial treatment to overcome cellular and molecular heterogeneity and prevent resistance caused by clonal evolution. PMID:23361103

  20. Cephalopod genomics

    DEFF Research Database (Denmark)

    Albertin, Caroline B.; Bonnaud, Laure; Brown, C. Titus

    2012-01-01

    The Cephalopod Sequencing Consortium (CephSeq Consortium) was established at a NESCent Catalysis Group Meeting, ``Paths to Cephalopod Genomics-Strategies, Choices, Organization,'' held in Durham, North Carolina, USA on May 24-27, 2012. Twenty-eight participants representing nine countries (Austria......, Australia, China, Denmark, France, Italy, Japan, Spain and the USA) met to address the pressing need for genome sequencing of cephalopod mollusks. This group, drawn from cephalopod biologists, neuroscientists, developmental and evolutionary biologists, materials scientists, bioinformaticians and researchers...... active in sequencing, assembling and annotating genomes, agreed on a set of cephalopod species of particular importance for initial sequencing and developed strategies and an organization (CephSeq Consortium) to promote this sequencing. The conclusions and recommendations of this meeting are described...

  1. Biomarkers in acute heart failure.

    Science.gov (United States)

    Mallick, Aditi; Januzzi, James L

    2015-06-01

    The care of patients with acutely decompensated heart failure is being reshaped by the availability and understanding of several novel and emerging heart failure biomarkers. The gold standard biomarkers in heart failure are B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide, which play an important role in the diagnosis, prognosis, and management of acute decompensated heart failure. Novel biomarkers that are increasingly involved in the processes of myocardial injury, neurohormonal activation, and ventricular remodeling are showing promise in improving diagnosis and prognosis among patients with acute decompensated heart failure. These include midregional proatrial natriuretic peptide, soluble ST2, galectin-3, highly-sensitive troponin, and midregional proadrenomedullin. There has also been an emergence of biomarkers for evaluation of acute decompensated heart failure that assist in the differential diagnosis of dyspnea, such as procalcitonin (for identification of acute pneumonia), as well as markers that predict complications of acute decompensated heart failure, such as renal injury markers. In this article, we will review the pathophysiology and usefulness of established and emerging biomarkers for the clinical diagnosis, prognosis, and management of acute decompensated heart failure. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  2. Genome Sequencing

    DEFF Research Database (Denmark)

    Sato, Shusei; Andersen, Stig Uggerhøj

    2014-01-01

    The current Lotus japonicus reference genome sequence is based on a hybrid assembly of Sanger TAC/BAC, Sanger shotgun and Illumina shotgun sequencing data generated from the Miyakojima-MG20 accession. It covers nearly all expressed L. japonicus genes and has been annotated mainly based on transcr......The current Lotus japonicus reference genome sequence is based on a hybrid assembly of Sanger TAC/BAC, Sanger shotgun and Illumina shotgun sequencing data generated from the Miyakojima-MG20 accession. It covers nearly all expressed L. japonicus genes and has been annotated mainly based...

  3. Perspectives of Integrative Cancer Genomics in Next Generation Sequencing Era

    Directory of Open Access Journals (Sweden)

    So Mee Kwon

    2012-06-01

    Full Text Available The explosive development of genomics technologies including microarrays and next generation sequencing (NGS has provided comprehensive maps of cancer genomes, including the expression of mRNAs and microRNAs, DNA copy numbers, sequence variations, and epigenetic changes. These genome-wide profiles of the genetic aberrations could reveal the candidates for diagnostic and/or prognostic biomarkers as well as mechanistic insights into tumor development and progression. Recent efforts to establish the huge cancer genome compendium and integrative omics analyses, so-called "integromics", have extended our understanding on the cancer genome, showing its daunting complexity and heterogeneity. However, the challenges of the structured integration, sharing, and interpretation of the big omics data still remain to be resolved. Here, we review several issues raised in cancer omics data analysis, including NGS, focusing particularly on the study design and analysis strategies. This might be helpful to understand the current trends and strategies of the rapidly evolving cancer genomics research.

  4. Biomarkers in inflammatory bowel diseases

    DEFF Research Database (Denmark)

    Bennike, Tue; Birkelund, Svend; Stensballe, Allan

    2014-01-01

    Unambiguous diagnosis of the two main forms of inflammatory bowel diseases (IBD): Ulcerative colitis (UC) and Crohn's disease (CD), represents a challenge in the early stages of the diseases. The diagnosis may be established several years after the debut of symptoms. Hence, protein biomarkers...... for early and accurate diagnostic could help clinicians improve treatment of the individual patients. Moreover, the biomarkers could aid physicians to predict disease courses and in this way, identify patients in need of intensive treatment. Patients with low risk of disease flares may avoid treatment...... with medications with the concomitant risk of adverse events. In addition, identification of disease and course specific biomarker profiles can be used to identify biological pathways involved in the disease development and treatment. Knowledge of disease mechanisms in general can lead to improved future...

  5. Biomarkers of replicative senescence revisited

    DEFF Research Database (Denmark)

    Nehlin, Jan

    2016-01-01

    Biomarkers of replicative senescence can be defined as those ultrastructural and physiological variations as well as molecules whose changes in expression, activity or function correlate with aging, as a result of the gradual exhaustion of replicative potential and a state of permanent cell cycle...... arrest. The biomarkers that characterize the path to an irreversible state of cell cycle arrest due to proliferative exhaustion may also be shared by other forms of senescence-inducing mechanisms. Validation of senescence markers is crucial in circumstances where quiescence or temporary growth arrest may...... be triggered or is thought to be induced. Pre-senescence biomarkers are also important to consider as their presence indicate that induction of aging processes is taking place. The bona fide pathway leading to replicative senescence that has been extensively characterized is a consequence of gradual reduction...

  6. Comparative Genomics

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 11; Issue 8. Comparative Genomics - A Powerful New Tool in Biology. Anand K Bachhawat. General Article Volume 11 Issue 8 August 2006 pp 22-40. Fulltext. Click here to view fulltext PDF. Permanent link:

  7. Biomarkers in scleroderma: Current status

    Directory of Open Access Journals (Sweden)

    Latika Gupta

    2017-01-01

    Full Text Available Scleroderma is an autoimmune disease characterized by indolent obliterative vasculopathy and widespread fibrosis. The two main morphological manifestations of the disease overlap and may make it difficult to separate activity from damage. Many patients, especially those with the limited subset of the disease, have an indolent course without clear-cut inflammatory manifestations. There is a felt need for validated biomarkers, which can differentiate activity from damage, and yet be sensitive to change with therapy. Multiplex arrays of biomarkers have ushered an era of targeted or personalized medicine based on phenotypic characteristics in an individual.

  8. Early-Phase Studies of Biomarkers

    DEFF Research Database (Denmark)

    Pepe, Margaret S.; Janes, Holly; Li, Christopher I.

    2016-01-01

    of a positive biomarker test in cases (true positive) to cost associated with a positive biomarker test in controls (false positive). Guidance is offered on soliciting the cost/benefit ratio. The calculations are based on the longstanding decision theory concept of providing a net benefit on average...... impact on patient outcomes of using the biomarker to make clinical decisions....

  9. Rostrocaudal Dynamics of CSF Biomarkers

    NARCIS (Netherlands)

    Tarnaris, A.; Toma, A.K.; Chapman, M.D.; Petzold, A.F.S.; Keir, G.; Kitchen, N.D.; Watkins, L.D.

    2011-01-01

    The rostrocaudal gradient (RCG) of markers present in cerebrospinal fluid (CSF) has not been studied adequately due to lack of appropriate control populations and ethical restrictions. The aim of this study is to understand the rostrocaudal gradient of CSF biomarkers. We contacted a study comparing

  10. Imaging Biomarkers for Adult Medulloblastomas

    DEFF Research Database (Denmark)

    Keil, V C; Warmuth-Metz, M; Reh, C

    2017-01-01

    BACKGROUND AND PURPOSE: The occurrence of medulloblastomas in adults is rare; nevertheless, these tumors can be subdivided into genetic and histologic entities each having distinct prognoses. This study aimed to identify MR imaging biomarkers to classify these entities and to uncover differences ...

  11. Biomarkers of satiation and satiety

    NARCIS (Netherlands)

    Graaf, de C.; Blom, W.A.M.; Smeets, P.A.M.; Stafleu, A.; Hendriks, H.F.J.

    2004-01-01

    This review's objective is to give a critical summary of studies that focused on physiologic measures relating to subjectively rated appetite, actual food intake, or both. Biomarkers of satiation and satiety may be used as a tool for assessing the satiating efficiency of foods and for understanding

  12. Bias in Peripheral Depression Biomarkers

    DEFF Research Database (Denmark)

    Carvalho, André F; Köhler, Cristiano A; Brunoni, André R

    2016-01-01

    BACKGROUND: To aid in the differentiation of individuals with major depressive disorder (MDD) from healthy controls, numerous peripheral biomarkers have been proposed. To date, no comprehensive evaluation of the existence of bias favoring the publication of significant results or inflating effect...

  13. Biomarkers of spontaneous preterm birth

    DEFF Research Database (Denmark)

    Polettini, Jossimara; Cobo, Teresa; Kacerovsky, Marian

    2017-01-01

    biomarkers associated with PTB published from January 2005 to March 2014. Retrieved citations (3631) were screened, and relevant studies (33) were selected for full-text reading. Ten studies were included in the review. Forty-two PTB-related proteins were reported, and RANTES and IL-10 (three studies...

  14. Accounting for control mislabeling in case-control biomarker studies.

    Science.gov (United States)

    Rantalainen, Mattias; Holmes, Chris C

    2011-12-02

    In biomarker discovery studies, uncertainty associated with case and control labels is often overlooked. By omitting to take into account label uncertainty, model parameters and the predictive risk can become biased, sometimes severely. The most common situation is when the control set contains an unknown number of undiagnosed, or future, cases. This has a marked impact in situations where the model needs to be well-calibrated, e.g., when the prediction performance of a biomarker panel is evaluated. Failing to account for class label uncertainty may lead to underestimation of classification performance and bias in parameter estimates. This can further impact on meta-analysis for combining evidence from multiple studies. Using a simulation study, we outline how conventional statistical models can be modified to address class label uncertainty leading to well-calibrated prediction performance estimates and reduced bias in meta-analysis. We focus on the problem of mislabeled control subjects in case-control studies, i.e., when some of the control subjects are undiagnosed cases, although the procedures we report are generic. The uncertainty in control status is a particular situation common in biomarker discovery studies in the context of genomic and molecular epidemiology, where control subjects are commonly sampled from the general population with an established expected disease incidence rate.

  15. Biomarkers in neonatology: the new "omics" of bronchopulmonary dysplasia.

    Science.gov (United States)

    Piersigilli, Fiammetta; Bhandari, Vineet

    2016-01-01

    Bronchopulmonary dysplasia (BPD) is a complex disorder resulting from gene-environmental interactions. An improved understanding of the pathogenesis of this most common chronic lung disease in infants has been made by utilizing animal models and correlating with human data. Currently, while some (vitamin A, caffeine) pharmacotherapeutic options are being utilized to ameliorate this condition, there is still no specific or effective treatment for BPD. It would be helpful for prognostication and targeted potential novel therapeutic strategies to identify those babies accurately who are at risk for developing this disease. A reliable biomarker would have the capacity to be detected in the initial phase of the disease, to allow early interventions to avoid or minimize the detrimental effects of the disease. This review will focus on human studies performed with the "omic" techniques, specifically genomics, epigenomics, microbiomics, transciptomics, proteomics and metabolomics, and summarize the information available in the literature, as it pertains to biomarker identification for BPD. Using "omics" technologies, investigators have reported markers that have the potential to be used as biomarkers of BPD: SPOCK2, VEGF -624C > G, VEGF -460T > C, mast cells specific markers, miR-219 pathway, miR-152, -30a-3p, -133b, -206, -7, lactate, taurine, trimethylamine-N-oxide, gluconate, myoinositol and alterations in surfactant lipid profile.

  16. Biomarkers of adult and developmental neurotoxicity

    International Nuclear Information System (INIS)

    Slikker, William; Bowyer, John F.

    2005-01-01

    Neurotoxicity may be defined as any adverse effect on the structure or function of the central and/or peripheral nervous system by a biological, chemical, or physical agent. A multidisciplinary approach is necessary to assess adult and developmental neurotoxicity due to the complex and diverse functions of the nervous system. The overall strategy for understanding developmental neurotoxicity is based on two assumptions: (1) significant differences in the adult versus the developing nervous system susceptibility to neurotoxicity exist and they are often developmental stage dependent; (2) a multidisciplinary approach using neurobiological, including gene expression assays, neurophysiological, neuropathological, and behavioral function is necessary for a precise assessment of neurotoxicity. Application of genomic approaches to developmental studies must use the same criteria for evaluating microarray studies as those in adults including consideration of reproducibility, statistical analysis, homogenous cell populations, and confirmation with non-array methods. A study using amphetamine to induce neurotoxicity supports the following: (1) gene expression data can help define neurotoxic mechanism(s) (2) gene expression changes can be useful biomarkers of effect, and (3) the site-selective nature of gene expression in the nervous system may mandate assessment of selective cell populations

  17. Personal genomics services: whose genomes?

    Science.gov (United States)

    Gurwitz, David; Bregman-Eschet, Yael

    2009-07-01

    New companies offering personal whole-genome information services over the internet are dynamic and highly visible players in the personal genomics field. For fees currently ranging from US$399 to US$2500 and a vial of saliva, individuals can now purchase online access to their individual genetic information regarding susceptibility to a range of chronic diseases and phenotypic traits based on a genome-wide SNP scan. Most of the companies offering such services are based in the United States, but their clients may come from nearly anywhere in the world. Although the scientific validity, clinical utility and potential future implications of such services are being hotly debated, several ethical and regulatory questions related to direct-to-consumer (DTC) marketing strategies of genetic tests have not yet received sufficient attention. For example, how can we minimize the risk of unauthorized third parties from submitting other people's DNA for testing? Another pressing question concerns the ownership of (genotypic and phenotypic) information, as well as the unclear legal status of customers regarding their own personal information. Current legislation in the US and Europe falls short of providing clear answers to these questions. Until the regulation of personal genomics services catches up with the technology, we call upon commercial providers to self-regulate and coordinate their activities to minimize potential risks to individual privacy. We also point out some specific steps, along the trustee model, that providers of DTC personal genomics services as well as regulators and policy makers could consider for addressing some of the concerns raised below.

  18. Biomarker Identification and Pathway Analysis by Serum Metabolomics of Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yingrong Chen

    2015-01-01

    Full Text Available Lung cancer is one of the most common causes of cancer death, for which no validated tumor biomarker is sufficiently accurate to be useful for diagnosis. Additionally, the metabolic alterations associated with the disease are unclear. In this study, we investigated the construction, interaction, and pathways of potential lung cancer biomarkers using metabolomics pathway analysis based on the Kyoto Encyclopedia of Genes and Genomes database and the Human Metabolome Database to identify the top altered pathways for analysis and visualization. We constructed a diagnostic model using potential serum biomarkers from patients with lung cancer. We assessed their specificity and sensitivity according to the area under the curve of the receiver operator characteristic (ROC curves, which could be used to distinguish patients with lung cancer from normal subjects. The pathway analysis indicated that sphingolipid metabolism was the top altered pathway in lung cancer. ROC curve analysis indicated that glycerophospho-N-arachidonoyl ethanolamine (GpAEA and sphingosine were potential sensitive and specific biomarkers for lung cancer diagnosis and prognosis. Compared with the traditional lung cancer diagnostic biomarkers carcinoembryonic antigen and cytokeratin 19 fragment, GpAEA and sphingosine were as good or more appropriate for detecting lung cancer. We report our identification of potential metabolic diagnostic and prognostic biomarkers of lung cancer and clarify the metabolic alterations in lung cancer.

  19. New and emerging prognostic and predictive genetic biomarkers in B-cell precursor acute lymphoblastic leukemia

    Science.gov (United States)

    Moorman, Anthony V.

    2016-01-01

    Acute lymphoblastic leukemia (ALL) is a heterogeneous disease at the genetic level. Chromosomal abnormalities are used as diagnostic, prognostic and predictive biomarkers to provide subtype, outcome and drug response information. t(12;21)/ETV6-RUNX1 and high hyper-diploidy are good-risk prognostic biomarkers whereas KMT2A (MLL) translocations, t(17;19)/TCF3-HLF, haploidy or low hypodiploidy are high-risk biomarkers. t(9;22)/BCR-ABL1 patients require targeted treatment (imatinib/dasatinib), whereas iAMP21 patients achieve better outcomes when treated intensively. High-risk genetic biomarkers are four times more prevalent in adults compared to children. The application of genomic technologies to cases without an established abnormality (B-other) reveals copy number alterations which can be used either individually or in combination as prognostic biomarkers. Transcriptome sequencing studies have identified a network of fusion genes involving kinase genes - ABL1, ABL2, PDGFRB, CSF1R, CRLF2, JAK2 and EPOR. In vitro and in vivo studies along with emerging clinical observations indicate that patients with a kinase-activating aberration may respond to treatment with small molecular inhibitors like imatinib/dasatinib and ruxolitinib. Further work is required to determine the true frequency of these abnormalities across the age spectrum and the optimal way to incorporate such inhibitors into protocols. In conclusion, genetic biomarkers are playing an increasingly important role in the management of patients with ALL. PMID:27033238

  20. Visualization for genomics: the Microbial Genome Viewer.

    NARCIS (Netherlands)

    Kerkhoven, R.; Enckevort, F.H.J. van; Boekhorst, J.; Molenaar, D; Siezen, R.J.

    2004-01-01

    SUMMARY: A Web-based visualization tool, the Microbial Genome Viewer, is presented that allows the user to combine complex genomic data in a highly interactive way. This Web tool enables the interactive generation of chromosome wheels and linear genome maps from genome annotation data stored in a

  1. Implementation of proteomic biomarkers: making it work.

    Science.gov (United States)

    Mischak, Harald; Ioannidis, John P A; Argiles, Angel; Attwood, Teresa K; Bongcam-Rudloff, Erik; Broenstrup, Mark; Charonis, Aristidis; Chrousos, George P; Delles, Christian; Dominiczak, Anna; Dylag, Tomasz; Ehrich, Jochen; Egido, Jesus; Findeisen, Peter; Jankowski, Joachim; Johnson, Robert W; Julien, Bruce A; Lankisch, Tim; Leung, Hing Y; Maahs, David; Magni, Fulvio; Manns, Michael P; Manolis, Efthymios; Mayer, Gert; Navis, Gerjan; Novak, Jan; Ortiz, Alberto; Persson, Frederik; Peter, Karlheinz; Riese, Hans H; Rossing, Peter; Sattar, Naveed; Spasovski, Goce; Thongboonkerd, Visith; Vanholder, Raymond; Schanstra, Joost P; Vlahou, Antonia

    2012-09-01

    While large numbers of proteomic biomarkers have been described, they are generally not implemented in medical practice. We have investigated the reasons for this shortcoming, focusing on hurdles downstream of biomarker verification, and describe major obstacles and possible solutions to ease valid biomarker implementation. Some of the problems lie in suboptimal biomarker discovery and validation, especially lack of validated platforms with well-described performance characteristics to support biomarker qualification. These issues have been acknowledged and are being addressed, raising the hope that valid biomarkers may start accumulating in the foreseeable future. However, successful biomarker discovery and qualification alone does not suffice for successful implementation. Additional challenges include, among others, limited access to appropriate specimens and insufficient funding, the need to validate new biomarker utility in interventional trials, and large communication gaps between the parties involved in implementation. To address this problem, we propose an implementation roadmap. The implementation effort needs to involve a wide variety of stakeholders (clinicians, statisticians, health economists, and representatives of patient groups, health insurance, pharmaceutical companies, biobanks, and regulatory agencies). Knowledgeable panels with adequate representation of all these stakeholders may facilitate biomarker evaluation and guide implementation for the specific context of use. This approach may avoid unwarranted delays or failure to implement potentially useful biomarkers, and may expedite meaningful contributions of the biomarker community to healthcare. © 2012 The Authors. European Journal of Clinical Investigation © 2012 Stichting European Society for Clinical Investigation Journal Foundation.

  2. Biomarkers of PTSD: military applications and considerations

    Directory of Open Access Journals (Sweden)

    Amy Lehrner

    2014-08-01

    Full Text Available Background: Although there are no established biomarkers for posttraumatic stress disorder (PTSD as yet, biological investigations of PTSD have made progress identifying the pathophysiology of PTSD. Given the biological and clinical complexity of PTSD, it is increasingly unlikely that a single biomarker of disease will be identified. Rather, investigations will more likely identify different biomarkers that indicate the presence of clinically significant PTSD symptoms, associate with risk for PTSD following trauma exposure, and predict or identify recovery. While there has been much interest in PTSD biomarkers, there has been less discussion of their potential clinical applications, and of the social, legal, and ethical implications of such biomarkers. Objective: This article will discuss possible applications of PTSD biomarkers, including the social, legal, and ethical implications of such biomarkers, with an emphasis on military applications. Method: Literature on applications of PTSD biomarkers and on potential ethical and legal implications will be reviewed. Results: Biologically informed research findings hold promise for prevention, assessment, treatment planning, and the development of prophylactic and treatment interventions. As with any biological indicator of disorder, there are potentially positive and negative clinical, social, legal, and ethical consequences of using such biomarkers. Conclusions: Potential clinical applications of PTSD biomarkers hold promise for clinicians, patients, and employers. The search for biomarkers of PTSD should occur in tandem with an interdisciplinary discussion regarding the potential implications of applying biological findings in clinical and employment settings.

  3. Biomarkers of PTSD: military applications and considerations.

    Science.gov (United States)

    Lehrner, Amy; Yehuda, Rachel

    2014-01-01

    Although there are no established biomarkers for posttraumatic stress disorder (PTSD) as yet, biological investigations of PTSD have made progress identifying the pathophysiology of PTSD. Given the biological and clinical complexity of PTSD, it is increasingly unlikely that a single biomarker of disease will be identified. Rather, investigations will more likely identify different biomarkers that indicate the presence of clinically significant PTSD symptoms, associate with risk for PTSD following trauma exposure, and predict or identify recovery. While there has been much interest in PTSD biomarkers, there has been less discussion of their potential clinical applications, and of the social, legal, and ethical implications of such biomarkers. This article will discuss possible applications of PTSD biomarkers, including the social, legal, and ethical implications of such biomarkers, with an emphasis on military applications. Literature on applications of PTSD biomarkers and on potential ethical and legal implications will be reviewed. Biologically informed research findings hold promise for prevention, assessment, treatment planning, and the development of prophylactic and treatment interventions. As with any biological indicator of disorder, there are potentially positive and negative clinical, social, legal, and ethical consequences of using such biomarkers. Potential clinical applications of PTSD biomarkers hold promise for clinicians, patients, and employers. The search for biomarkers of PTSD should occur in tandem with an interdisciplinary discussion regarding the potential implications of applying biological findings in clinical and employment settings.

  4. Implementation of proteomic biomarkers: making it work

    Science.gov (United States)

    Mischak, Harald; Ioannidis, John PA; Argiles, Angel; Attwood, Teresa K; Bongcam-Rudloff, Erik; Broenstrup, Mark; Charonis, Aristidis; Chrousos, George P; Delles, Christian; Dominiczak, Anna; Dylag, Tomasz; Ehrich, Jochen; Egido, Jesus; Findeisen, Peter; Jankowski, Joachim; Johnson, Robert W; Julien, Bruce A; Lankisch, Tim; Leung, Hing Y; Maahs, David; Magni, Fulvio; Manns, Michael P; Manolis, Efthymios; Mayer, Gert; Navis, Gerjan; Novak, Jan; Ortiz, Alberto; Persson, Frederik; Peter, Karlheinz; Riese, Hans H; Rossing, Peter; Sattar, Naveed; Spasovski, Goce; Thongboonkerd, Visith; Vanholder, Raymond; Schanstra, Joost P; Vlahou, Antonia

    2012-01-01

    While large numbers of proteomic biomarkers have been described, they are generally not implemented in medical practice. We have investigated the reasons for this shortcoming, focusing on hurdles downstream of biomarker verification, and describe major obstacles and possible solutions to ease valid biomarker implementation. Some of the problems lie in suboptimal biomarker discovery and validation, especially lack of validated platforms with well-described performance characteristics to support biomarker qualification. These issues have been acknowledged and are being addressed, raising the hope that valid biomarkers may start accumulating in the foreseeable future. However, successful biomarker discovery and qualification alone does not suffice for successful implementation. Additional challenges include, among others, limited access to appropriate specimens and insufficient funding, the need to validate new biomarker utility in interventional trials, and large communication gaps between the parties involved in implementation. To address this problem, we propose an implementation roadmap. The implementation effort needs to involve a wide variety of stakeholders (clinicians, statisticians, health economists, and representatives of patient groups, health insurance, pharmaceutical companies, biobanks, and regulatory agencies). Knowledgeable panels with adequate representation of all these stakeholders may facilitate biomarker evaluation and guide implementation for the specific context of use. This approach may avoid unwarranted delays or failure to implement potentially useful biomarkers, and may expedite meaningful contributions of the biomarker community to healthcare. PMID:22519700

  5. Proteomic and metabolomic approaches to biomarker discovery

    CERN Document Server

    Issaq, Haleem J

    2013-01-01

    Proteomic and Metabolomic Approaches to Biomarker Discovery demonstrates how to leverage biomarkers to improve accuracy and reduce errors in research. Disease biomarker discovery is one of the most vibrant and important areas of research today, as the identification of reliable biomarkers has an enormous impact on disease diagnosis, selection of treatment regimens, and therapeutic monitoring. Various techniques are used in the biomarker discovery process, including techniques used in proteomics, the study of the proteins that make up an organism, and metabolomics, the study of chemical fingerprints created from cellular processes. Proteomic and Metabolomic Approaches to Biomarker Discovery is the only publication that covers techniques from both proteomics and metabolomics and includes all steps involved in biomarker discovery, from study design to study execution.  The book describes methods, and presents a standard operating procedure for sample selection, preparation, and storage, as well as data analysis...

  6. Applications of Support Vector Machine (SVM) Learning in Cancer Genomics.

    Science.gov (United States)

    Huang, Shujun; Cai, Nianguang; Pacheco, Pedro Penzuti; Narrandes, Shavira; Wang, Yang; Xu, Wayne

    2018-01-01

    Machine learning with maximization (support) of separating margin (vector), called support vector machine (SVM) learning, is a powerful classification tool that has been used for cancer genomic classification or subtyping. Today, as advancements in high-throughput technologies lead to production of large amounts of genomic and epigenomic data, the classification feature of SVMs is expanding its use in cancer genomics, leading to the discovery of new biomarkers, new drug targets, and a better understanding of cancer driver genes. Herein we reviewed the recent progress of SVMs in cancer genomic studies. We intend to comprehend the strength of the SVM learning and its future perspective in cancer genomic applications. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  7. Chronic Obstructive Pulmonary Disease Biomarkers

    Directory of Open Access Journals (Sweden)

    Tatsiana Beiko

    2016-04-01

    Full Text Available Despite significant decreases in morbidity and mortality of cardiovascular diseases (CVD and cancers, morbidity and cost associated with chronic obstructive pulmonary disease (COPD continue to be increasing. Failure to improve disease outcomes has been related to the paucity of interventions improving survival. Insidious onset and slow progression halter research successes in developing disease-modifying therapies. In part, the difficulty in finding new therapies is because of the extreme heterogeneity within recognized COPD phenotypes. Novel biomarkers are necessary to help understand the natural history and pathogenesis of the different COPD subtypes. A more accurate phenotyping and the ability to assess the therapeutic response to new interventions and pharmaceutical agents may improve the statistical power of longitudinal clinical studies. In this study, we will review known candidate biomarkers for COPD, proposed pathways of pathogenesis, and future directions in the field.

  8. Glycoscience aids in biomarker discovery

    Directory of Open Access Journals (Sweden)

    Serenus Hua1,2 & Hyun Joo An1,2,*

    2012-06-01

    Full Text Available The glycome consists of all glycans (or carbohydrates within abiological system, and modulates a wide range of important biologicalactivities, from protein folding to cellular communications.The mining of the glycome for disease markers representsa new paradigm for biomarker discovery; however, this effortis severely complicated by the vast complexity and structuraldiversity of glycans. This review summarizes recent developmentsin analytical technology and methodology as applied tothe fields of glycomics and glycoproteomics. Mass spectrometricstrategies for glycan compositional profiling are described, as arepotential refinements which allow structure-specific profiling.Analytical methods that can discern protein glycosylation at aspecific site of modification are also discussed in detail.Biomarker discovery applications are shown at each level ofanalysis, highlighting the key role that glycoscience can play inhelping scientists understand disease biology.

  9. Ancient genomics

    DEFF Research Database (Denmark)

    Der Sarkissian, Clio; Allentoft, Morten Erik; Avila Arcos, Maria del Carmen

    2015-01-01

    throughput of next generation sequencing platforms and the ability to target short and degraded DNA molecules. Many ancient specimens previously unsuitable for DNA analyses because of extensive degradation can now successfully be used as source materials. Additionally, the analytical power obtained...... by increasing the number of sequence reads to billions effectively means that contamination issues that have haunted aDNA research for decades, particularly in human studies, can now be efficiently and confidently quantified. At present, whole genomes have been sequenced from ancient anatomically modern humans...

  10. Marine genomics

    DEFF Research Database (Denmark)

    Oliveira Ribeiro, Ângela Maria; Foote, Andrew David; Kupczok, Anne

    2017-01-01

    Marine ecosystems occupy 71% of the surface of our planet, yet we know little about their diversity. Although the inventory of species is continually increasing, as registered by the Census of Marine Life program, only about 10% of the estimated two million marine species are known. This lag......-throughput sequencing approaches have been helping to improve our knowledge of marine biodiversity, from the rich microbial biota that forms the base of the tree of life to a wealth of plant and animal species. In this review, we present an overview of the applications of genomics to the study of marine life, from...

  11. Looking for biomarkers of Hg exposure by transcriptome analysis in the aquatic plant Elodea nuttallii

    Directory of Open Access Journals (Sweden)

    Regier N.

    2013-04-01

    Full Text Available Recently developed genomics tools have a promising potential to identify early biomarkers of exposure to toxicants. In the present work we used transcriptome analysis (RNA-seq of Elodea nuttallii –an invasive rooted macrophyte that is able to accumulate large amounts of metals- to identify biomarkers of Hg exposure. RNA-seq allowed identification of genes affected by Hg exposure and also unraveled plant response to the toxic metal: a change in energy/reserve metabolism caused by the inhibition of photosynthesis, and an adaptation of homeostasis networks to control accumulation of Hg. Data were validated by RT-qPCR and selected genes were further tested as biomarkers. Samples exposed in the field and to natural contaminated sediments clustered well with samples exposed to low metal concentrations under laboratory conditions. Our data suggest that this plant and/or this approach could be useful to develop new tests for water and sediment quality assessment.

  12. Potential biomarker panels in overall breast cancer management: advancements by multilevel diagnostics.

    Science.gov (United States)

    Girotra, Shantanu; Yeghiazaryan, Kristina; Golubnitschaja, Olga

    2016-09-01

    Breast cancer (BC) prevalence has reached an epidemic scale with half a million deaths annually. Current deficits in BC management include predictive and preventive approaches, optimized screening programs, individualized patient profiling, highly sensitive detection technologies for more precise diagnostics and therapy monitoring, individualized prediction and effective treatment of BC metastatic disease. To advance BC management, paradigm shift from delayed to predictive, preventive and personalized medical services is essential. Corresponding step forwards requires innovative multilevel diagnostics procuring specific panels of validated biomarkers. Here, we discuss current instrumental advancements including genomics, proteomics, epigenetics, miRNA, metabolomics, circulating tumor cells and cancer stem cells with a focus on biomarker discovery and multilevel diagnostic panels. A list of the recommended biomarker candidates is provided.

  13. Biomarkers in adult posthemorrhagic hydrocephalus.

    Science.gov (United States)

    Hua, Cong; Zhao, Gang

    2017-08-01

    Posthemorrhagic hydrocephalus is a severe complication following intracranial hemorrhage. Posthemorrhagic hydrocephalus is often associated with high morbidity and mortality and serves as an important clinical predictor of adverse outcomes after intracranial hemorrhage. Currently, no effective medical intervention exists to improve functional outcomes in posthemorrhagic hydrocephalus patients because little is still known about the mechanisms of posthemorrhagic hydrocephalus pathogenesis. Because a better understanding of the posthemorrhagic hydrocephalus pathogenesis would facilitate development of clinical treatments, this is an active research area. The purpose of this review is to describe recent progress in elucidation of molecular mechanisms that cause posthemorrhagic hydrocephalus. What we are certain of is that the entry of blood into the ventricular system and subarachnoid space results in release of lytic blood products which cause a series of physiological and pathological changes in the brain. Blood components that can be linked to pathology would serve as disease biomarkers. From studies of posthemorrhagic hydrocephalus, such biomarkers are known to mutually synergize to initiate and promote posthemorrhagic hydrocephalus progression. These findings suggest that modulation of biomarker expression or function may benefit posthemorrhagic hydrocephalus patients.

  14. Genomic rearrangements of PTEN in prostate cancer

    Directory of Open Access Journals (Sweden)

    Sopheap ePhin

    2013-09-01

    Full Text Available The phosphatase and tensin homolog gene on chromosome 10q23.3 (PTEN is a negative regulator of the PIK3/Akt survival pathway and is the most frequently deleted tumor suppressor gene in prostate cancer. Monoallelic loss of PTEN is present in up to 60% of localized prostate cancers and complete loss of PTEN in prostate cancer is linked to metastasis and androgen independent progression. Studies on the genomic status of PTEN in prostate cancer initially used a two-color fluorescence in-situ hybridization (FISH assay for PTEN copy number detection in formalin fixed paraffin embedded tissue preparations. More recently, a four-color FISH assay containing two additional control probes flanking the PTEN locus with a lower false-positive rate was reported. Combined with the detection of other critical genomic biomarkers for prostate cancer such as ERG, AR, and MYC, the evaluation of PTEN genomic status has proven to be invaluable for patient stratification and management. Although less frequent than allelic deletions, point mutations in the gene and epigenetic silencing are also known to contribute to loss of PTEN function, and ultimately to prostate cancer initiation. Overall, it is clear that PTEN is a powerful biomarker for prostate cancer. Used as a companion diagnostic for emerging therapeutic drugs, FISH analysis of PTEN is promisingly moving human prostate cancer closer to more effective cancer management and therapies.

  15. Biomarkers for Early Detection of Clinically Relevant Prostate Cancer. A Multi-Institutional Validation Trial

    Science.gov (United States)

    2016-10-01

    aim 2: Evaluate a panel of four-kallikrein plasma-based markers to determine the presence of or progression to clinically relevant prostate cancer...and sent to Genomic Health, Inc. for processing. Task 3: Analysis of scientific Aim 2: Evaluate a panel of four-kallikrein plasma-based markers to...site: FHCRC) PCA3 and the TMPRSS2:ERG fusion are prostate cancer-specific biomarkers that hold promise for stratifying risk in the setting of AS

  16. Robust prediction of anti-cancer drug sensitivity and sensitivity-specific biomarker.

    Directory of Open Access Journals (Sweden)

    Heewon Park

    Full Text Available The personal genomics era has attracted a large amount of attention for anti-cancer therapy by patient-specific analysis. Patient-specific analysis enables discovery of individual genomic characteristics for each patient, and thus we can effectively predict individual genetic risk of disease and perform personalized anti-cancer therapy. Although the existing methods for patient-specific analysis have successfully uncovered crucial biomarkers, their performance takes a sudden turn for the worst in the presence of outliers, since the methods are based on non-robust manners. In practice, clinical and genomic alterations datasets usually contain outliers from various sources (e.g., experiment error, coding error, etc. and the outliers may significantly affect the result of patient-specific analysis. We propose a robust methodology for patient-specific analysis in line with the NetwrokProfiler. In the proposed method, outliers in high dimensional gene expression levels and drug response datasets are simultaneously controlled by robust Mahalanobis distance in robust principal component space. Thus, we can effectively perform for predicting anti-cancer drug sensitivity and identifying sensitivity-specific biomarkers for individual patients. We observe through Monte Carlo simulations that the proposed robust method produces outstanding performances for predicting response variable in the presence of outliers. We also apply the proposed methodology to the Sanger dataset in order to uncover cancer biomarkers and predict anti-cancer drug sensitivity, and show the effectiveness of our method.

  17. Biomarker Qualification: Toward a Multiple Stakeholder Framework for Biomarker Development, Regulatory Acceptance, and Utilization.

    Science.gov (United States)

    Amur, S; LaVange, L; Zineh, I; Buckman-Garner, S; Woodcock, J

    2015-07-01

    The discovery, development, and use of biomarkers for a variety of drug development purposes are areas of tremendous interest and need. Biomarkers can become accepted for use through submission of biomarker data during the drug approval process. Another emerging pathway for acceptance of biomarkers is via the biomarker qualification program developed by the Center for Drug Evaluation and Research (CDER, US Food and Drug Administration). Evidentiary standards are needed to develop and evaluate various types of biomarkers for their intended use and multiple stakeholders, including academia, industry, government, and consortia must work together to help develop this evidence. The article describes various types of biomarkers that can be useful in drug development and evidentiary considerations that are important for qualification. A path forward for coordinating efforts to identify and explore needed biomarkers is proposed for consideration. © 2015 American Society for Clinical Pharmacology and Therapeutics.

  18. Biomarkers of carcinogen exposure and early effects.

    OpenAIRE

    2006-01-01

    The purpose of this review is to summarise the current situation regarding the types and uses of biomarkers of exposure and effect for the main classes of food-derived genotoxic carcinogens, and to consider some aspects of the intercomparison between these biomarkers. The biomarkers of exposure and early effects of carcinogens that have been most extensively developed are those for genotoxic agents and for compounds that generate hydroxyl radicals and other reactive radical species, and it is...

  19. Biomarkers of HIV-associated Cancer

    OpenAIRE

    Flepisi, Brian Thabile; Bouic, Patrick; Sissolak, Gerhard; Rosenkranz, Bernd

    2014-01-01

    Cancer biomarkers have provided great opportunities for improving the management of cancer patients by enhancing the efficiency of early detection, diagnosis, and efficacy of treatment. Every cell type has a unique molecular signature, referred to as biomarkers, which are identifiable characteristics such as levels or activities of a myriad of genes, proteins, or other molecular features. Biomarkers can facilitate the molecular definition of cancer, provide information about the course of can...

  20. Biomarkers of PTSD: military applications and considerations

    OpenAIRE

    Amy Lehrner; Rachel Yehuda

    2014-01-01

    Background: Although there are no established biomarkers for posttraumatic stress disorder (PTSD) as yet, biological investigations of PTSD have made progress identifying the pathophysiology of PTSD. Given the biological and clinical complexity of PTSD, it is increasingly unlikely that a single biomarker of disease will be identified. Rather, investigations will more likely identify different biomarkers that indicate the presence of clinically significant PTSD symptoms, associate with risk fo...

  1. [Acute lymphoblastic leukemia: a genomic perspective].

    Science.gov (United States)

    Jiménez-Morales, Silvia; Hidalgo-Miranda, Alfredo; Ramírez-Bello, Julián

    In parallel to the human genome sequencing project, several technological platforms have been developed that let us gain insight into the genome structure of human entities, as well as evaluate their usefulness in the clinical approach of the patient. Thus, in acute lymphoblastic leukemia (ALL), the most common pediatric malignancy, genomic tools promise to be useful to detect patients at high risk of relapse, either at diagnosis or during treatment (minimal residual disease), and they also increase the possibility to identify cases at risk of adverse reactions to chemotherapy. Therefore, the physician could offer patient-tailored therapeutic schemes. A clear example of the useful genomic tools is the identification of single nucleotide polymorphisms (SNPs) in the thiopurine methyl transferase (TPMT) gene, where the presence of two null alleles (homozygous or compound heterozygous) indicates the need to reduce the dose of mercaptopurine by up to 90% to avoid toxic effects which could lead to the death of the patient. In this review, we provide an overview of the genomic perspective of ALL, describing some strategies that contribute to the identification of biomarkers with potential clinical application. Copyright © 2017 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  2. Cardiovascular biomarkers in clinical studies of type 2 diabetes

    DEFF Research Database (Denmark)

    Baldassarre, M P A; Andersen, A; Consoli, A

    2018-01-01

    biomarkers and 3) novel biomarkers (oxidative stress and endothelial dysfunction biomarkers). Within each category we present the currently best validated biomarkers with special focus on the population of interest (type 2 diabetes). For each individual biomarker, the physiological role, the validation...

  3. Ensembl Genomes 2016: more genomes, more complexity.

    Science.gov (United States)

    Kersey, Paul Julian; Allen, James E; Armean, Irina; Boddu, Sanjay; Bolt, Bruce J; Carvalho-Silva, Denise; Christensen, Mikkel; Davis, Paul; Falin, Lee J; Grabmueller, Christoph; Humphrey, Jay; Kerhornou, Arnaud; Khobova, Julia; Aranganathan, Naveen K; Langridge, Nicholas; Lowy, Ernesto; McDowall, Mark D; Maheswari, Uma; Nuhn, Michael; Ong, Chuang Kee; Overduin, Bert; Paulini, Michael; Pedro, Helder; Perry, Emily; Spudich, Giulietta; Tapanari, Electra; Walts, Brandon; Williams, Gareth; Tello-Ruiz, Marcela; Stein, Joshua; Wei, Sharon; Ware, Doreen; Bolser, Daniel M; Howe, Kevin L; Kulesha, Eugene; Lawson, Daniel; Maslen, Gareth; Staines, Daniel M

    2016-01-04

    Ensembl Genomes (http://www.ensemblgenomes.org) is an integrating resource for genome-scale data from non-vertebrate species, complementing the resources for vertebrate genomics developed in the context of the Ensembl project (http://www.ensembl.org). Together, the two resources provide a consistent set of programmatic and interactive interfaces to a rich range of data including reference sequence, gene models, transcriptional data, genetic variation and comparative analysis. This paper provides an update to the previous publications about the resource, with a focus on recent developments. These include the development of new analyses and views to represent polyploid genomes (of which bread wheat is the primary exemplar); and the continued up-scaling of the resource, which now includes over 23 000 bacterial genomes, 400 fungal genomes and 100 protist genomes, in addition to 55 genomes from invertebrate metazoa and 39 genomes from plants. This dramatic increase in the number of included genomes is one part of a broader effort to automate the integration of archival data (genome sequence, but also associated RNA sequence data and variant calls) within the context of reference genomes and make it available through the Ensembl user interfaces. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  4. Rodent malaria parasites : genome organization & comparative genomics

    NARCIS (Netherlands)

    Kooij, Taco W.A.

    2006-01-01

    The aim of the studies described in this thesis was to investigate the genome organization of rodent malaria parasites (RMPs) and compare the organization and gene content of the genomes of RMPs and the human malaria parasite P. falciparum. The release of the complete genome sequence of P.

  5. A Review of the “Omics” Approach to Biomarkers of Oxidative Stress in Oryza sativa

    Directory of Open Access Journals (Sweden)

    Su Shiung Lam

    2013-04-01

    Full Text Available Physiological and ecological constraints that cause the slow growth and depleted production of crops have raised a major concern in the agriculture industry as they represent a possible threat of short food supply in the future. The key feature that regulates the stress signaling pathway is always related to the reactive oxygen species (ROS. The accumulation of ROS in plant cells would leave traces of biomarkers at the genome, proteome, and metabolome levels, which could be identified with the recent technological breakthrough coupled with improved performance of bioinformatics. This review highlights the recent breakthrough in molecular strategies (comprising transcriptomics, proteomics, and metabolomics in identifying oxidative stress biomarkers and the arising opportunities and obstacles observed in research on biomarkers in rice. The major issue in incorporating bioinformatics to validate the biomarkers from different omic platforms for the use of rice-breeding programs is also discussed. The development of powerful techniques for identification of oxidative stress-related biomarkers and the integration of data from different disciplines shed light on the oxidative response pathways in plants.

  6. Metabolomics, Nutrition, and Potential Biomarkers of Food Quality, Intake, and Health Status.

    Science.gov (United States)

    Sébédio, Jean-Louis

    Diet, dietary patterns, and other environmental factors such as exposure to toxins are playing an important role in the prevention/development of many diseases, like obesity, type 2 diabetes, and consequently on the health status of individuals. A major challenge nowadays is to identify novel biomarkers to detect as early as possible metabolic dysfunction and to predict evolution of health status in order to refine nutritional advices to specific population groups. Omics technologies such as genomics, transcriptomics, proteomics, and metabolomics coupled with statistical and bioinformatics tools have already shown great potential in this research field even if so far only few biomarkers have been validated. For the past two decades, important analytical techniques have been developed to detect as many metabolites as possible in human biofluids such as urine, blood, and saliva. In the field of food science and nutrition, many studies have been carried out for food authenticity, quality, and safety, as well as for food processing. Furthermore, metabolomic investigations have been carried out to discover new early biomarkers of metabolic dysfunction and predictive biomarkers of developing pathologies (obesity, metabolic syndrome, type-2 diabetes, etc.). Great emphasis is also placed in the development of methodologies to identify and validate biomarkers of nutrients exposure. © 2017 Elsevier Inc. All rights reserved.

  7. Biomarker Development for TLR4 Agonists

    National Research Council Canada - National Science Library

    Persing, David H

    2004-01-01

    .... To monitor the effectiveness of immunoprophylaxis in human trials, it may become necessary to develop surrogate biomarkers of protection since experimental challenge endpoints are not readily available...

  8. Serum Antibody Biomarkers for ASD

    Science.gov (United States)

    2015-10-01

    typically developing control. US, unaffected sibling control. 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a...typically developing (TD) children (e.g., Warren et al., 1990; Singh, 2009). The goal of this study is to identify a serum antibody biomarker for ASD using...50% less IgG1 antibody in ASD boys vs . TD boys (p=0.0096). The level of ASD1 binding to the AM group was the same as to the ASD boys. These data

  9. Funding Opportunity: Genomic Data Centers

    Science.gov (United States)

    Funding Opportunity CCG, Funding Opportunity Center for Cancer Genomics, CCG, Center for Cancer Genomics, CCG RFA, Center for cancer genomics rfa, genomic data analysis network, genomic data analysis network centers,

  10. Semi-automated literature mining to identify putative biomarkers of disease from multiple biofluids

    Science.gov (United States)

    2014-01-01

    Background Computational methods for mining of biomedical literature can be useful in augmenting manual searches of the literature using keywords for disease-specific biomarker discovery from biofluids. In this work, we develop and apply a semi-automated literature mining method to mine abstracts obtained from PubMed to discover putative biomarkers of breast and lung cancers in specific biofluids. Methodology A positive set of abstracts was defined by the terms ‘breast cancer’ and ‘lung cancer’ in conjunction with 14 separate ‘biofluids’ (bile, blood, breastmilk, cerebrospinal fluid, mucus, plasma, saliva, semen, serum, synovial fluid, stool, sweat, tears, and urine), while a negative set of abstracts was defined by the terms ‘(biofluid) NOT breast cancer’ or ‘(biofluid) NOT lung cancer.’ More than 5.3 million total abstracts were obtained from PubMed and examined for biomarker-disease-biofluid associations (34,296 positive and 2,653,396 negative for breast cancer; 28,355 positive and 2,595,034 negative for lung cancer). Biological entities such as genes and proteins were tagged using ABNER, and processed using Python scripts to produce a list of putative biomarkers. Z-scores were calculated, ranked, and used to determine significance of putative biomarkers found. Manual verification of relevant abstracts was performed to assess our method’s performance. Results Biofluid-specific markers were identified from the literature, assigned relevance scores based on frequency of occurrence, and validated using known biomarker lists and/or databases for lung and breast cancer [NCBI’s On-line Mendelian Inheritance in Man (OMIM), Cancer Gene annotation server for cancer genomics (CAGE), NCBI’s Genes & Disease, NCI’s Early Detection Research Network (EDRN), and others]. The specificity of each marker for a given biofluid was calculated, and the performance of our semi-automated literature mining method assessed for breast and lung cancer

  11. Exploring Other Genomes: Bacteria.

    Science.gov (United States)

    Flannery, Maura C.

    2001-01-01

    Points out the importance of genomes other than the human genome project and provides information on the identified bacterial genomes Pseudomonas aeuroginosa, Leprosy, Cholera, Meningitis, Tuberculosis, Bubonic Plague, and plant pathogens. Considers the computer's use in genome studies. (Contains 14 references.) (YDS)

  12. Pathogenesis and biomarkers of carcinogenesis in ulcerative colitis

    DEFF Research Database (Denmark)

    Thorsteinsdottir, Sigrun; Gudjonsson, Thorkell; Nielsen, Ole Haagen

    2011-01-01

    on the current understanding of the pathogenesis of ulcerative colitis-associated colorectal cancer and how this knowledge can be transferred into patient management to assist clinicians and pathologists in identifying patients with ulcerative colitis who have an increased risk of colorectal cancer. Inflammation......One of the most serious complications of ulcerative colitis is the development of colorectal cancer. Screening patients with ulcerative colitis by standard histological examination of random intestinal biopsy samples might be inefficient as a method of cancer surveillance. This Review focuses......-driven mechanisms of DNA damage, including the generation and effects of reactive oxygen species, microsatellite instability, telomere shortening and chromosomal instability, are reviewed, as are the molecular responses to genomic stress. We also discuss how these mechanisms can be translated into usable biomarkers...

  13. The Somatic Genomic Landscape of Glioblastoma

    Science.gov (United States)

    Brennan, Cameron W.; Verhaak, Roel G.W.; McKenna, Aaron; Campos, Benito; Noushmehr, Houtan; Salama, Sofie R.; Zheng, Siyuan; Chakravarty, Debyani; Sanborn, J. Zachary; Berman, Samuel H.; Beroukhim, Rameen; Bernard, Brady; Wu, Chang-Jiun; Genovese, Giannicola; Shmulevich, Ilya; Barnholtz-Sloan, Jill; Zou, Lihua; Vegesna, Rahulsimham; Shukla, Sachet A.; Ciriello, Giovanni; Yung, WK; Zhang, Wei; Sougnez, Carrie; Mikkelsen, Tom; Aldape, Kenneth; Bigner, Darell D.; Van Meir, Erwin G.; Prados, Michael; Sloan, Andrew; Black, Keith L.; Eschbacher, Jennifer; Finocchiaro, Gaetano; Friedman, William; Andrews, David W.; Guha, Abhijit; Iacocca, Mary; O’Neill, Brian P.; Foltz, Greg; Myers, Jerome; Weisenberger, Daniel J.; Penny, Robert; Kucherlapati, Raju; Perou, Charles M.; Hayes, D. Neil; Gibbs, Richard; Marra, Marco; Mills, Gordon B.; Lander, Eric; Spellman, Paul; Wilson, Richard; Sander, Chris; Weinstein, John; Meyerson, Matthew; Gabriel, Stacey; Laird, Peter W.; Haussler, David; Getz, Gad; Chin, Lynda

    2013-01-01

    We describe the landscape of somatic genomic alterations based on multi-dimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer. PMID:24120142

  14. Proteomic Biomarkers for Spontaneous Preterm Birth

    DEFF Research Database (Denmark)

    Kacerovsky, Marian; Lenco, Juraj; Musilova, Ivana

    2014-01-01

    This review aimed to identify, synthesize, and analyze the findings of studies on proteomic biomarkers for spontaneous preterm birth (PTB). Three electronic databases (Medline, Embase, and Scopus) were searched for studies in any language reporting the use of proteomic biomarkers for PTB published...

  15. Biomarkers of Renal Function : Towards Clinical Actionability

    NARCIS (Netherlands)

    Binnenmars, S Heleen; Hijmans, R S; Navis, G; de Borst, M H

    This review provides an overview of the clinical value of themost relevant renal biomarkers, focusing on two main clinical conditions: acute kidney injury and chronic kidney disease. We categorize biomarkers according to their actionability, in terms of a documented response to treatment in relation

  16. MicroRNA biomarkers in glioblastoma

    DEFF Research Database (Denmark)

    Hermansen, Simon Kjær; Kristensen, Bjarne Winther

    2013-01-01

    tissues. Understanding these alterations is key to developing new biomarkers and intelligent treatment strategies. This review presents an overview of current knowledge about miRNA alterations in glioblastoma while focusing on the clinical future of miRNAs as biomarkers and discussing the strengths...

  17. Stable isotopes and biomarkers in microbial ecology

    NARCIS (Netherlands)

    Boschker, H.T.S.; Middelburg, J.J.

    2002-01-01

    The use of biomarkers in combination with stable isotope analysis is a new approach in microbial ecology and a number of papers on a variety of subjects have appeared. We will first discuss the techniques for analysing stable isotopes in biomarkers, primarily gas chromatography-combustion-isotope

  18. DNA Methylation Biomarkers: Cancer and Beyond

    Directory of Open Access Journals (Sweden)

    Thomas Mikeska

    2014-09-01

    Full Text Available Biomarkers are naturally-occurring characteristics by which a particular pathological process or disease can be identified or monitored. They can reflect past environmental exposures, predict disease onset or course, or determine a patient’s response to therapy. Epigenetic changes are such characteristics, with most epigenetic biomarkers discovered to date based on the epigenetic mark of DNA methylation. Many tissue types are suitable for the discovery of DNA methylation biomarkers including cell-based samples such as blood and tumor material and cell-free DNA samples such as plasma. DNA methylation biomarkers with diagnostic, prognostic and predictive power are already in clinical trials or in a clinical setting for cancer. Outside cancer, strong evidence that complex disease originates in early life is opening up exciting new avenues for the detection of DNA methylation biomarkers for adverse early life environment and for estimation of future disease risk. However, there are a number of limitations to overcome before such biomarkers reach the clinic. Nevertheless, DNA methylation biomarkers have great potential to contribute to personalized medicine throughout life. We review the current state of play for DNA methylation biomarkers, discuss the barriers that must be crossed on the way to implementation in a clinical setting, and predict their future use for human disease.

  19. Bias in emerging biomarkers for bipolar disorder

    DEFF Research Database (Denmark)

    Carvalho, A F; Köhler, C A; Fernandes, B S

    2016-01-01

    BACKGROUND: To date no comprehensive evaluation has appraised the likelihood of bias or the strength of the evidence of peripheral biomarkers for bipolar disorder (BD). Here we performed an umbrella review of meta-analyses of peripheral non-genetic biomarkers for BD. METHOD: The Pubmed/Medline, E...

  20. Imaging biomarker roadmap for cancer studies

    NARCIS (Netherlands)

    O'Connor, James P. B.; Aboagye, Eric O.; Adams, Judith E.; Aerts, Hugo J. W. L.; Barrington, Sally F.; Beer, Ambros J.; Boellaard, Ronald; Bohndiek, Sarah E.; Brady, Michael; Brown, Gina; Buckley, David L.; Chenevert, Thomas L.; Clarke, Laurence P.; Collette, Sandra; Cook, Gary J.; Desouza, Nandita M.; Dickson, John C.; Dive, Caroline; Evelhoch, Jeffrey L.; Faivre-Finn, Corinne; Gallagher, Ferdia A.; Gilbert, Fiona J.; Gillies, Robert J.; Goh, Vicky; Griffiths, J. R.; Groves, Ashley M.; Halligan, Steve; Harris, Adrian L.; Hawkes, David J.; Hoekstra, Otto S.; Huang, Erich P.; Hutton, Brian F.; Jackson, Edward F.; Jayson, Gordon C.; Jones, Andrew; Koh, Dow-Mu; Lacombe, Denis; Lambin, Philippe; Lassau, Nathalie; Leach, Martin O.; Lee, Ting-Yim; Leen, Edward L.; Lewis, Jason S.; Liu, Yan; Lythgoe, Mark F.; Manoharan, Prakash; Maxwell, Ross J.; Miles, Kenneth A.; Morgan, Bruno; Morris, Steve; Ng, Tony; Padhani, Anwar R.; Parker, Geoff J. M.; Partridge, Mike; Pathak, Arvind P.; Peet, Andrew C.; Punwani, Shonit; Reynolds, Andrew R.; Robinson, Simon P.; Shankar, Lalitha K.; Sharma, Ricky A.; Soloviev, Dmitry; Stroobants, Sigrid G.; Sullivan, Daniel C.; Taylor, Stuart A.; Tofts, Paul S.; Tozer, Gillian M.; van Herk, Marcel B.; Walker-Samuel, Simon; Wason, James; Williams, Kaye J.; Workman, Paul; Yankeelov, Thomas E.; Brindle, Kevin M.; McShane, Lisa M.; Jackson, Alan; Waterton, John C.

    Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and

  1. Implementation of proteomic biomarkers : Making it work

    NARCIS (Netherlands)

    Mischak, Harald; Ioannidis, John P. A.; Argiles, Angel; Attwood, Teresa K.; Bongcam-Rudloff, Erik; Broenstrup, Mark; Charonis, Aristidis; Chrousos, George P.; Delles, Christian; Dominiczak, Anna; Dylag, Tomasz; Ehrich, Jochen; Egido, Jesus; Findeisen, Peter; Jankowski, Joachim; Johnson, Robert W.; Julien, Bruce A.; Lankisch, Tim; Leung, Hing Y.; Maahs, David; Magni, Fulvio; Manns, Michael P.; Manolis, Efthymios; Mayer, Gert; Navis, Gerarda; Novak, Jan; Ortiz, Alberto; Persson, Frederik; Peter, Karlheinz; Riese, Hans H.; Rossing, Peter; Sattar, Naveed; Spasovski, Goce; Thongboonkerd, Visith; Vanholder, Raymond; Schanstra, Joost P.; Vlahou, Antonia

    Eur J Clin Invest 2012; 42 (9): 10271036 Abstract While large numbers of proteomic biomarkers have been described, they are generally not implemented in medical practice. We have investigated the reasons for this shortcoming, focusing on hurdles downstream of biomarker verification, and describe

  2. Functional genomics in renal transplantation and chronic kidney disease

    International Nuclear Information System (INIS)

    Wilflingseder, J.

    2010-01-01

    For the past decade, the development of genomic technology has revolutionized modern biological research. Functional genomic analyses enable biologists to study genetic events on a genome wide scale. Examples of applications are gene discovery, biomarker determination, disease classification, and drug target identification. Global expression profiles performed with microarrays enable a better understanding of molecular signature of human disease, including acute and chronic kidney disease. About 10 % of the population in western industrialized nations suffers from chronic kidney disease (CKD). Treatment of end stage renal disease, the final stage of CKD is performed by either hemo- or peritoneal dialysis or renal transplantation. The preferred treatment is renal transplantation, because of the higher quality of life. But the pathophysiology of the disease on a molecular level is not well enough understood and early biomarkers for acute and chronic kidney disease are missing. In my studies I focused on genomics of allograft biopsies, prevention of delayed graft function after renal transplantation, anemia after renal transplantation, biocompatibility of hemodialysis membranes and peritoneal dialysis fluids and cardiovascular diseases and bone disorders in CKD patients. Gene expression profiles, pathway analysis and protein-protein interaction networks were used to elucidate the underlying pathophysiological mechanism of the disease or phenomena, identifying early biomarkers or predictors of disease state and potentially drug targets. In summery my PhD thesis represents the application of functional genomic analyses in chronic kidney disease and renal transplantation. The results provide a deeper view into the molecular and cellular mechanisms of kidney disease. Nevertheless, future multicenter collaborative studies, meta-analyses of existing data, incorporation of functional genomics into large-scale prospective clinical trials are needed and will give biomedical

  3. Subject-based steroid profiling and the determination of novel biomarkers for DHT and DHEA misuse in sports.

    Science.gov (United States)

    Van Renterghem, Pieter; Van Eenoo, Peter; Sottas, Pierre-Edouard; Saugy, Martial; Delbeke, Frans

    2010-01-01

    Doping with natural steroids can be detected by evaluating the urinary concentrations and ratios of several endogenous steroids. Since these biomarkers of steroid doping are known to present large inter-individual variations, monitoring of individual steroid profiles over time allows switching from population-based towards subject-based reference ranges for improved detection. In an Athlete Biological Passport (ABP), biomarkers data are collated throughout the athlete's sporting career and individual thresholds defined adaptively. For now, this approach has been validated on a limited number of markers of steroid doping, such as the testosterone (T) over epitestosterone (E) ratio to detect T misuse in athletes. Additional markers are required for other endogenous steroids like dihydrotestosterone (DHT) and dehydroepiandrosterone (DHEA). By combining comprehensive steroid profiles composed of 24 steroid concentrations with Bayesian inference techniques for longitudinal profiling, a selection was made for the detection of DHT and DHEA misuse. The biomarkers found were rated according to relative response, parameter stability, discriminative power, and maximal detection time. This analysis revealed DHT/E, DHT/5β-androstane-3α,17β-diol and 5α-androstane-3α,17β-diol/5β-androstane-3α,17β-diol as best biomarkers for DHT administration and DHEA/E, 16α-hydroxydehydroepiandrosterone/E, 7β-hydroxydehydroepiandrosterone/E and 5β-androstane-3α,17β-diol/5α-androstane-3α,17β-diol for DHEA. The selected biomarkers were found suitable for individual referencing. A drastic overall increase in sensitivity was obtained. The use of multiple markers as formalized in an Athlete Steroidal Passport (ASP) can provide firm evidence of doping with endogenous steroids. Copyright © 2010 John Wiley & Sons, Ltd.

  4. Biomarkers in molecular epidemiology study of oral squamous cell carcinoma in the era of precision medicine

    Directory of Open Access Journals (Sweden)

    Qing-Hao Zhu

    2017-01-01

    Full Text Available Oral cancer, which occurs in the mouth, lips, and tongue, is a multifactorial disease whose etiology involves environment, genetic, and epigenetic factors. Tobacco use and alcohol consumption are regarded as the primary risk factors for oral squamous cell carcinoma (OSCC, and betel use, other chemicals, radiation, environmental, and genetics are reported as relevant risk factors for oral carcinogenesis. The human papillomavirus infection is an independent risk factor. Traditional epidemiology studies have revealed that environmental carcinogens are risk factors for OSCC. Molecular epidemiology studies have revealed that the susceptibility to OSCC is influenced by both environmental and genetic risk factors. However, the details and mechanisms of risk factors involved in OSCC are unclear. Advanced methods and techniques used in human genome studies provide great opportunities for researchers to explore and identify (a the details of such risk factors and (b genetic susceptibility involved in OSCC. Human genome epidemiology is a new branch of epidemiology, which leads the epidemiology study from the molecular epidemiology era into the era of genome-wide association study. In the era of precision medicine, molecular epidemiology studies should focus on biomarkers for cancer genomics and their potential utility in clinical practice. Here, we briefly reviewed several molecular epidemiology studies of OSCC, focusing on biomarkers as valuable utility in risk assessment, clinical screening, diagnosis, and prognosis prediction of OSCC in the era of precision medicine.

  5. Genomics With Cloud Computing

    OpenAIRE

    Sukhamrit Kaur; Sandeep Kaur

    2015-01-01

    Abstract Genomics is study of genome which provides large amount of data for which large storage and computation power is needed. These issues are solved by cloud computing that provides various cloud platforms for genomics. These platforms provides many services to user like easy access to data easy sharing and transfer providing storage in hundreds of terabytes more computational power. Some cloud platforms are Google genomics DNAnexus and Globus genomics. Various features of cloud computin...

  6. Fluid biomarkers in multiple system atrophy

    DEFF Research Database (Denmark)

    Laurens, Brice; Constantinescu, Radu; Freeman, Roy

    2015-01-01

    Despite growing research efforts, no reliable biomarker currently exists for the diagnosis and prognosis of multiple system atrophy (MSA). Such biomarkers are urgently needed to improve diagnostic accuracy, prognostic guidance and also to serve as efficacy measures or surrogates of target...... engagement for future clinical trials. We here review candidate fluid biomarkers for MSA and provide considerations for further developments and harmonization of standard operating procedures. A PubMed search was performed until April 24, 2015 to review the literature with regard to candidate blood...... and cerebrospinal fluid (CSF) biomarkers for MSA. Abstracts of 1760 studies were retrieved and screened for eligibility. The final list included 60 studies assessing fluid biomarkers in patients with MSA. Most studies have focused on alpha-synuclein, markers of axonal degeneration or catecholamines. Their results...

  7. RECENT ADVANCES IN BIOMARKERS IN SEVERE BURNS.

    Science.gov (United States)

    Ruiz-Castilla, Mireia; Roca, Oriol; Masclans, Joan R; Barret, Joan P

    2016-02-01

    The pathophysiology of burn injuries is tremendously complex. A thorough understanding is essential for correct treatment of the burned area and also to limit the appearance of organ dysfunction, which, in fact, is a key determinant of morbidity and mortality. In this context, research into biomarkers may play a major role. Biomarkers have traditionally been considered an important area of medical research: the measurement of certain biomarkers has led to a better understanding of pathophysiology, while others have been used either to assess the effectiveness of specific treatments or for prognostic purposes. Research into biomarkers may help to improve the prognosis of patients with severe burn injury. The aim of the present clinical review is to discuss new evidence of the value of biomarkers in this setting.

  8. Diagnostic and prognostic epigenetic biomarkers in cancer.

    Science.gov (United States)

    Costa-Pinheiro, Pedro; Montezuma, Diana; Henrique, Rui; Jerónimo, Carmen

    2015-01-01

    Growing cancer incidence and mortality worldwide demands development of accurate biomarkers to perfect detection, diagnosis, prognostication and monitoring. Urologic (prostate, bladder, kidney), lung, breast and colorectal cancers are the most common and despite major advances in their characterization, this has seldom translated into biomarkers amenable for clinical practice. Epigenetic alterations are innovative cancer biomarkers owing to stability, frequency, reversibility and accessibility in body fluids, entailing great potential of assay development to assist in patient management. Several studies identified putative epigenetic cancer biomarkers, some of which have been commercialized. However, large multicenter validation studies are required to foster translation to the clinics. Herein we review the most promising epigenetic detection, diagnostic, prognostic and predictive biomarkers for the most common cancers.

  9. The Indian Consensus Document on cardiac biomarker

    Directory of Open Access Journals (Sweden)

    I. Satyamurthy

    2014-01-01

    Full Text Available Despite recent advances, the diagnosis and management of heart failure evades the clinicians. The etiology of congestive heart failure (CHF in the Indian scenario comprises of coronary artery disease, diabetes mellitus and hypertension. With better insights into the pathophysiology of CHF, biomarkers have evolved rapidly and received diagnostic and prognostic value. In CHF biomarkers prove as measures of the extent of pathophysiological derangement; examples include biomarkers of myocyte necrosis, myocardial remodeling, neurohormonal activation, etc. In CHF biomarkers act as indicators for the presence, degree of severity and prognosis of the disease, they may be employed in combination with the present conventional clinical assessments. These make the biomarkers feasible options against the present expensive measurements and may provide clinical benefits.

  10. Biomarkers: in medicine, drug discovery, and environmental health

    National Research Council Canada - National Science Library

    Vaidya, Vishal S; Bonventre, Joseph V

    2010-01-01

    ... Identification Using Mass Spectrometry Sample Preparation Protein Quantitation Examples of Biomarker Discovery and Evaluation Challenges in Proteomic Biomarker Discovery The Road Forward: Targeted ...

  11. Genome Maps, a new generation genome browser.

    Science.gov (United States)

    Medina, Ignacio; Salavert, Francisco; Sanchez, Rubén; de Maria, Alejandro; Alonso, Roberto; Escobar, Pablo; Bleda, Marta; Dopazo, Joaquín

    2013-07-01

    Genome browsers have gained importance as more genomes and related genomic information become available. However, the increase of information brought about by new generation sequencing technologies is, at the same time, causing a subtle but continuous decrease in the efficiency of conventional genome browsers. Here, we present Genome Maps, a genome browser that implements an innovative model of data transfer and management. The program uses highly efficient technologies from the new HTML5 standard, such as scalable vector graphics, that optimize workloads at both server and client sides and ensure future scalability. Thus, data management and representation are entirely carried out by the browser, without the need of any Java Applet, Flash or other plug-in technology installation. Relevant biological data on genes, transcripts, exons, regulatory features, single-nucleotide polymorphisms, karyotype and so forth, are imported from web services and are available as tracks. In addition, several DAS servers are already included in Genome Maps. As a novelty, this web-based genome browser allows the local upload of huge genomic data files (e.g. VCF or BAM) that can be dynamically visualized in real time at the client side, thus facilitating the management of medical data affected by privacy restrictions. Finally, Genome Maps can easily be integrated in any web application by including only a few lines of code. Genome Maps is an open source collaborative initiative available in the GitHub repository (https://github.com/compbio-bigdata-viz/genome-maps). Genome Maps is available at: http://www.genomemaps.org.

  12. Break Breast Cancer Addiction by CRISPR/Cas9 Genome Editing.

    Science.gov (United States)

    Yang, Haitao; Jaeger, MariaLynn; Walker, Averi; Wei, Daniel; Leiker, Katie; Weitao, Tao

    2018-01-01

    Breast cancer is the leading diagnosed cancer for women globally. Evolution of breast cancer in tumorigenesis, metastasis and treatment resistance appears to be driven by the aberrant gene expression and protein degradation encoded by the cancer genomes. The uncontrolled cancer growth relies on these cellular events, thus constituting the cancerous programs and rendering the addiction towards them. These programs are likely the potential anticancer biomarkers for Personalized Medicine of breast cancer. This review intends to delineate the impact of the CRSPR/Cas-mediated genome editing in identification and validation of these anticancer biomarkers. It reviews the progress in three aspects of CRISPR/Cas9-mediated editing of the breast cancer genomes: Somatic genome editing, transcription and protein degradation addictions.

  13. PET Metabolic Biomarkers for Cancer

    Directory of Open Access Journals (Sweden)

    Etienne Croteau

    2016-01-01

    Full Text Available The body's main fuel sources are fats, carbohydrates (glucose, proteins, and ketone bodies. It is well known that an important hallmark of cancer cells is the overconsumption of glucose. Positron emission tomography (PET imaging using the glucose analog 18 F-fluorodeoxyglucose ( 18 F-FDG has been a powerful cancer diagnostic tool for many decades. Apart from surgery, chemotherapy and radiotherapy represent the two main domains for cancer therapy, targeting tumor proliferation, cell division, and DNA replication–-all processes that require a large amount of energy. Currently, in vivo clinical imaging of metabolism is performed almost exclusively using PET radiotracers that assess oxygen consumption and mechanisms of energy substrate consumption. This paper reviews the utility of PET imaging biomarkers for the detection of cancer proliferation, vascularization, metabolism, treatment response, and follow-up after radiation therapy, chemotherapy, and chemotherapy-related side effects.

  14. JGI Fungal Genomics Program

    Energy Technology Data Exchange (ETDEWEB)

    Grigoriev, Igor V.

    2011-03-14

    Genomes of energy and environment fungi are in focus of the Fungal Genomic Program at the US Department of Energy Joint Genome Institute (JGI). Its key project, the Genomics Encyclopedia of Fungi, targets fungi related to plant health (symbionts, pathogens, and biocontrol agents) and biorefinery processes (cellulose degradation, sugar fermentation, industrial hosts), and explores fungal diversity by means of genome sequencing and analysis. Over 50 fungal genomes have been sequenced by JGI to date and released through MycoCosm (www.jgi.doe.gov/fungi), a fungal web-portal, which integrates sequence and functional data with genome analysis tools for user community. Sequence analysis supported by functional genomics leads to developing parts list for complex systems ranging from ecosystems of biofuel crops to biorefineries. Recent examples of such 'parts' suggested by comparative genomics and functional analysis in these areas are presented here

  15. Genomic Encyclopedia of Fungi

    Energy Technology Data Exchange (ETDEWEB)

    Grigoriev, Igor

    2012-08-10

    Genomes of fungi relevant to energy and environment are in focus of the Fungal Genomic Program at the US Department of Energy Joint Genome Institute (JGI). Its key project, the Genomics Encyclopedia of Fungi, targets fungi related to plant health (symbionts, pathogens, and biocontrol agents) and biorefinery processes (cellulose degradation, sugar fermentation, industrial hosts), and explores fungal diversity by means of genome sequencing and analysis. Over 150 fungal genomes have been sequenced by JGI to date and released through MycoCosm (www.jgi.doe.gov/fungi), a fungal web-portal, which integrates sequence and functional data with genome analysis tools for user community. Sequence analysis supported by functional genomics leads to developing parts list for complex systems ranging from ecosystems of biofuel crops to biorefineries. Recent examples of such parts suggested by comparative genomics and functional analysis in these areas are presented here.

  16. Clinical significance of BRAF non-V600E mutations on the therapeutic effects of anti-EGFR monoclonal antibody treatment in patients with pretreated metastatic colorectal cancer: the Biomarker Research for anti-EGFR monoclonal Antibodies by Comprehensive Cancer genomics (BREAC) study.

    Science.gov (United States)

    Shinozaki, Eiji; Yoshino, Takayuki; Yamazaki, Kentaro; Muro, Kei; Yamaguchi, Kensei; Nishina, Tomohiro; Yuki, Satoshi; Shitara, Kohei; Bando, Hideaki; Mimaki, Sachiyo; Nakai, Chikako; Matsushima, Koutatsu; Suzuki, Yutaka; Akagi, Kiwamu; Yamanaka, Takeharu; Nomura, Shogo; Fujii, Satoshi; Esumi, Hiroyasu; Sugiyama, Masaya; Nishida, Nao; Mizokami, Masashi; Koh, Yasuhiro; Abe, Yukiko; Ohtsu, Atsushi; Tsuchihara, Katsuya

    2017-11-07

    Patients with BRAF V600E -mutated metastatic colorectal cancer (mCRC) have a poorer prognosis as well as resistance to anti-EGFR antibodies. However, it is unclear whether BRAF mutations other than BRAF V600E (BRAF non-V600E mutations) contribute to anti-EGFR antibody resistance. This study was composed of exploratory and inference cohorts. Candidate biomarkers identified by whole exome sequencing from super-responders and nonresponders in the exploratory cohort were validated by targeted resequencing for patients who received anti-EGFR antibody in the inference cohort. In the exploratory cohort, 31 candidate biomarkers, including KRAS/NRAS/BRAF mutations, were identified. Targeted resequencing of 150 patients in the inference cohort revealed 40 patients with RAS (26.7%), 9 patients with BRAF V600E (6.0%), and 7 patients with BRAF non-V600E mutations (4.7%), respectively. The response rates in RAS, BRAF V600E , and BRAF non-V600E were lower than those in RAS/BRAF wild-type (2.5%, 0%, and 0% vs 31.9%). The median PFS in BRAF non-V600E mutations was 2.4 months, similar to that in RAS or BRAF V600E mutations (2.1 and 1.6 months) but significantly worse than that in wild-type RAS/BRAF (5.9 months). Although BRAF non-V600E mutations identified were a rare and unestablished molecular subtype, certain BRAF non-V600E mutations might contribute to a lesser benefit of anti-EGFR monoclonal antibody treatment.

  17. CBD: a biomarker database for colorectal cancer.

    Science.gov (United States)

    Zhang, Xueli; Sun, Xiao-Feng; Cao, Yang; Ye, Benchen; Peng, Qiliang; Liu, Xingyun; Shen, Bairong; Zhang, Hong

    2018-01-01

    Colorectal cancer (CRC) biomarker database (CBD) was established based on 870 identified CRC biomarkers and their relevant information from 1115 original articles in PubMed published from 1986 to 2017. In this version of the CBD, CRC biomarker data were collected, sorted, displayed and analysed. The CBD with the credible contents as a powerful and time-saving tool provide more comprehensive and accurate information for further CRC biomarker research. The CBD was constructed under MySQL server. HTML, PHP and JavaScript languages have been used to implement the web interface. The Apache was selected as HTTP server. All of these web operations were implemented under the Windows system. The CBD could provide to users the multiple individual biomarker information and categorized into the biological category, source and application of biomarkers; the experiment methods, results, authors and publication resources; the research region, the average age of cohort, gender, race, the number of tumours, tumour location and stage. We only collect data from the articles with clear and credible results to prove the biomarkers are useful in the diagnosis, treatment or prognosis of CRC. The CBD can also provide a professional platform to researchers who are interested in CRC research to communicate, exchange their research ideas and further design high-quality research in CRC. They can submit their new findings to our database via the submission page and communicate with us in the CBD.Database URL: http://sysbio.suda.edu.cn/CBD/.

  18. Using gene co-expression network analysis to predict biomarkers for chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Borlawsky Tara B

    2010-10-01

    Full Text Available Abstract Background Chronic lymphocytic leukemia (CLL is the most common adult leukemia. It is a highly heterogeneous disease, and can be divided roughly into indolent and progressive stages based on classic clinical markers. Immunoglobin heavy chain variable region (IgVH mutational status was found to be associated with patient survival outcome, and biomarkers linked to the IgVH status has been a focus in the CLL prognosis research field. However, biomarkers highly correlated with IgVH mutational status which can accurately predict the survival outcome are yet to be discovered. Results In this paper, we investigate the use of gene co-expression network analysis to identify potential biomarkers for CLL. Specifically we focused on the co-expression network involving ZAP70, a well characterized biomarker for CLL. We selected 23 microarray datasets corresponding to multiple types of cancer from the Gene Expression Omnibus (GEO and used the frequent network mining algorithm CODENSE to identify highly connected gene co-expression networks spanning the entire genome, then evaluated the genes in the co-expression network in which ZAP70 is involved. We then applied a set of feature selection methods to further select genes which are capable of predicting IgVH mutation status from the ZAP70 co-expression network. Conclusions We have identified a set of genes that are potential CLL prognostic biomarkers IL2RB, CD8A, CD247, LAG3 and KLRK1, which can predict CLL patient IgVH mutational status with high accuracies. Their prognostic capabilities were cross-validated by applying these biomarker candidates to classify patients into different outcome groups using a CLL microarray datasets with clinical information.

  19. Sequencing-based breast cancer diagnostics as an alternative to routine biomarkers.

    Science.gov (United States)

    Rantalainen, Mattias; Klevebring, Daniel; Lindberg, Johan; Ivansson, Emma; Rosin, Gustaf; Kis, Lorand; Celebioglu, Fuat; Fredriksson, Irma; Czene, Kamila; Frisell, Jan; Hartman, Johan; Bergh, Jonas; Grönberg, Henrik

    2016-11-30

    Sequencing-based breast cancer diagnostics have the potential to replace routine biomarkers and provide molecular characterization that enable personalized precision medicine. Here we investigate the concordance between sequencing-based and routine diagnostic biomarkers and to what extent tumor sequencing contributes clinically actionable information. We applied DNA- and RNA-sequencing to characterize tumors from 307 breast cancer patients with replication in up to 739 patients. We developed models to predict status of routine biomarkers (ER, HER2,Ki-67, histological grade) from sequencing data. Non-routine biomarkers, including mutations in BRCA1, BRCA2 and ERBB2(HER2), and additional clinically actionable somatic alterations were also investigated. Concordance with routine diagnostic biomarkers was high for ER status (AUC = 0.95;AUC(replication) = 0.97) and HER2 status (AUC = 0.97;AUC(replication) = 0.92). The transcriptomic grade model enabled classification of histological grade 1 and histological grade 3 tumors with high accuracy (AUC = 0.98;AUC(replication) = 0.94). Clinically actionable mutations in BRCA1, BRCA2 and ERBB2(HER2) were detected in 5.5% of patients, while 53% had genomic alterations matching ongoing or concluded breast cancer studies. Sequencing-based molecular profiling can be applied as an alternative to histopathology to determine ER and HER2 status, in addition to providing improved tumor grading and clinically actionable mutations and molecular subtypes. Our results suggest that sequencing-based breast cancer diagnostics in a near future can replace routine biomarkers.

  20. Genomics With Cloud Computing

    Directory of Open Access Journals (Sweden)

    Sukhamrit Kaur

    2015-04-01

    Full Text Available Abstract Genomics is study of genome which provides large amount of data for which large storage and computation power is needed. These issues are solved by cloud computing that provides various cloud platforms for genomics. These platforms provides many services to user like easy access to data easy sharing and transfer providing storage in hundreds of terabytes more computational power. Some cloud platforms are Google genomics DNAnexus and Globus genomics. Various features of cloud computing to genomics are like easy access and sharing of data security of data less cost to pay for resources but still there are some demerits like large time needed to transfer data less network bandwidth.

  1. Biomarkers in DILI: one more step forward

    Directory of Open Access Journals (Sweden)

    Mercedes Robles-Díaz

    2016-08-01

    Full Text Available Despite being relatively rare, drug-induced liver injury (DILI is a serious condition, both for the individual patient due to the risk of acute liver failure, and for the drug development industry and regulatory agencies due to associations with drug development attritions, black box warnings and postmarketing withdrawals. A major limitation in DILI diagnosis and prediction is the current lack of specific biomarkers. Despite refined usage of traditional liver biomarkers in DILI, reliable disease outcome predictions are still difficult to make. These limitations have driven the growing interest in developing new more sensitive and specific DILI biomarkers, which can improve early DILI prediction, diagnosis and course of action. Several promising DILI biomarker candidates have been discovered to date, including mechanistic-based biomarker candidates such as glutamate dehydrogenase, high-mobility group box 1 protein and keratin-18, which can also provide information on the injury mechanism of different causative agents. Furthermore, microRNAs have received much attention lately as potential non-invasive DILI biomarker candidates, in particular miR-122. Advances in omics technologies offer a new approach for biomarker exploration studies. The ability to screen a large number of molecules (for example metabolites, proteins or DNA simultaneously enables the identification of ‘toxicity signatures’, which may be used to enhance preclinical safety assessments and disease diagnostics. Omics-based studies can also provide information on the underlying mechanisms of distinct forms of DILI that may further facilitate the identification of early diagnostic biomarkers and safer implementation of personalized medicine. In this review we summarize recent advances in the area of DILI biomarker studies.

  2. Biomarkers for equine joint injury and osteoarthritis.

    Science.gov (United States)

    McIlwraith, C Wayne; Kawcak, Christopher E; Frisbie, David D; Little, Christopher B; Clegg, Peter D; Peffers, Mandy J; Karsdal, Morten A; Ekman, Stina; Laverty, Sheila; Slayden, Richard A; Sandell, Linda J; Lohmander, L S; Kraus, Virginia B

    2018-03-01

    We report the results of a symposium aimed at identifying validated biomarkers that can be used to complement clinical observations for diagnosis and prognosis of joint injury leading to equine osteoarthritis (OA). Biomarkers might also predict pre-fracture change that could lead to catastrophic bone failure in equine athletes. The workshop was attended by leading scientists in the fields of equine and human musculoskeletal biomarkers to enable cross-disciplinary exchange and improve knowledge in both. Detailed proceedings with strategic planning was written, added to, edited and referenced to develop this manuscript. The most recent information from work in equine and human osteoarthritic biomarkers was accumulated, including the use of personalized healthcare to stratify OA phenotypes, transcriptome analysis of anterior cruciate ligament (ACL) and meniscal injuries in the human knee. The spectrum of "wet" biomarker assays that are antibody based that have achieved usefulness in both humans and horses, imaging biomarkers and the role they can play in equine and human OA was discussed. Prediction of musculoskeletal injury in the horse remains a challenge, and the potential usefulness of spectroscopy, metabolomics, proteomics, and development of biobanks to classify biomarkers in different stages of equine and human OA were reviewed. The participants concluded that new information and studies in equine musculoskeletal biomarkers have potential translational value for humans and vice versa. OA is equally important in humans and horses, and the welfare issues associated with catastrophic musculoskeletal injury in horses add further emphasis to the need for good validated biomarkers in the horse. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:823-831, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  3. Cardiac Biomarkers and Cycling Race

    Directory of Open Access Journals (Sweden)

    Caroline Le Goff, Jean-François Kaux, Sébastien Goffaux, Etienne Cavalier

    2015-06-01

    Full Text Available In cycling as in other types of strenuous exercise, there exists a risk of sudden death. It is important both to understand its causes and to see if the behavior of certain biomarkers might highlight athletes at risk. Many reports describe changes in biomarkers after strenuous exercise (Nie et al., 2011, but interpreting these changes, and notably distinguishing normal physiological responses from pathological changes, is not easy. Here we have focused on the kinetics of different cardiac biomarkers: creatin kinase (CK, creating kinase midbrain (CK-MB, myoglobin (MYO, highly sensitive troponin T (hs-TnT and N-terminal brain natriuretic peptide (NT-proBNP. The population studied was a group of young trained cyclists participating in a 177-km cycling race. The group of individuals was selected for maximal homogeneity. Their annual training volume was between 10,000 and 16,000 kilometers. The rhythm of races is comparable and averages 35 km/h, depending on the race’s difficulty. The cardiac frequency was recorded via a heart rate monitor. Three blood tests were taken. The first blood test, T0, was taken approximately 2 hours before the start of the race and was intended to gather values which would act as references for the following tests. The second blood test, T1, was realized within 5 minutes of their arrival. The third and final blood test, T3, was taken 3 hours following their arrival. The CK, CK-MB, MYO, hs-TnT and NT-proBNP were measured on the Roche Diagnostic modular E (Manhein, Germany. For the statistical analysis, an ANOVA and post hoc test of Scheffé were calculated with the Statistica Software version 9.1. We noticed an important significant variation in the cardiac frequency between T0 and T1 (p < 0.0001, T0 and T3 (p < 0.0001, and T1 and T3 (p < 0.01. Table 1 shows the results obtained for the different biomarkers. CK and CK-MB showed significant variation between T0-T1 and T0-T3 (p < 0.0001. Myoglobin increased significantly

  4. Mining biomarker information in biomedical literature

    Directory of Open Access Journals (Sweden)

    Younesi Erfan

    2012-12-01

    Full Text Available Abstract Background For selection and evaluation of potential biomarkers, inclusion of already published information is of utmost importance. In spite of significant advancements in text- and data-mining techniques, the vast knowledge space of biomarkers in biomedical text has remained unexplored. Existing named entity recognition approaches are not sufficiently selective for the retrieval of biomarker information from the literature. The purpose of this study was to identify textual features that enhance the effectiveness of biomarker information retrieval for different indication areas and diverse end user perspectives. Methods A biomarker terminology was created and further organized into six concept classes. Performance of this terminology was optimized towards balanced selectivity and specificity. The information retrieval performance using the biomarker terminology was evaluated based on various combinations of the terminology's six classes. Further validation of these results was performed on two independent corpora representing two different neurodegenerative diseases. Results The current state of the biomarker terminology contains 119 entity classes supported by 1890 different synonyms. The result of information retrieval shows improved retrieval rate of informative abstracts, which is achieved by including clinical management terms and evidence of gene/protein alterations (e.g. gene/protein expression status or certain polymorphisms in combination with disease and gene name recognition. When additional filtering through other classes (e.g. diagnostic or prognostic methods is applied, the typical high number of unspecific search results is significantly reduced. The evaluation results suggest that this approach enables the automated identification of biomarker information in the literature. A demo version of the search engine SCAIView, including the biomarker retrieval, is made available to the public through http

  5. Molecular Characterization of Gastric Carcinoma: Therapeutic Implications for Biomarkers and Targets

    Directory of Open Access Journals (Sweden)

    Lionel Kankeu Fonkoua

    2018-03-01

    Full Text Available Palliative chemotherapy is the mainstay of treatment of advanced gastric carcinoma (GC. Monoclonal antibodies including trastuzumab, ramucirumab, and pembrolizumab have been shown to provide additional benefits. However, the clinical outcomes are often unpredictable and they can vary widely among patients. Currently, no biomarker is available for predicting treatment response in the individual patient except human epidermal growth factor receptor 2 (HER2 amplification and programmed death-ligand 1 (PD-L1 expression for effectiveness of trastuzumab and pembrolizumab, respectively. Multi-platform molecular analysis of cancer, including GC, may help identify predictive biomarkers to guide selection of therapeutic agents. Molecular classification of GC by The Cancer Genome Atlas Research Network and the Asian Cancer Research Group is expected to identify therapeutic targets and predictive biomarkers. Complementary to molecular characterization of GC is molecular profiling by expression analysis and genomic sequencing of tumor DNA. Initial analysis of patients with gastroesophageal carcinoma demonstrates that the ratio of progression-free survival (PFS on molecular profile (MP-based treatment to PFS on treatment prior to molecular profiling exceeds 1.3, suggesting the potential value of MP in guiding selection of individualized therapy. Future strategies aiming to integrate molecular classification and profiling of tumors with therapeutic agents for achieving the goal of personalized treatment of GC are indicated.

  6. Molecular Characterization of Gastric Carcinoma: Therapeutic Implications for Biomarkers and Targets.

    Science.gov (United States)

    Kankeu Fonkoua, Lionel; Yee, Nelson S

    2018-03-09

    Palliative chemotherapy is the mainstay of treatment of advanced gastric carcinoma (GC). Monoclonal antibodies including trastuzumab, ramucirumab, and pembrolizumab have been shown to provide additional benefits. However, the clinical outcomes are often unpredictable and they can vary widely among patients. Currently, no biomarker is available for predicting treatment response in the individual patient except human epidermal growth factor receptor 2 (HER2) amplification and programmed death-ligand 1 (PD-L1) expression for effectiveness of trastuzumab and pembrolizumab, respectively. Multi-platform molecular analysis of cancer, including GC, may help identify predictive biomarkers to guide selection of therapeutic agents. Molecular classification of GC by The Cancer Genome Atlas Research Network and the Asian Cancer Research Group is expected to identify therapeutic targets and predictive biomarkers. Complementary to molecular characterization of GC is molecular profiling by expression analysis and genomic sequencing of tumor DNA. Initial analysis of patients with gastroesophageal carcinoma demonstrates that the ratio of progression-free survival (PFS) on molecular profile (MP)-based treatment to PFS on treatment prior to molecular profiling exceeds 1.3, suggesting the potential value of MP in guiding selection of individualized therapy. Future strategies aiming to integrate molecular classification and profiling of tumors with therapeutic agents for achieving the goal of personalized treatment of GC are indicated.

  7. A Novel Panel of Serum Biomarkers for MPM Diagnosis

    Directory of Open Access Journals (Sweden)

    A. Bonotti

    2017-01-01

    Full Text Available Exposure to asbestos is the main cause of malignant pleural mesothelioma (MPM, a highly aggressive cancer of the pleura. Since the only tools for early detection are based on radiological tests, some authors focused on serum markers (i.e., mesothelin. The aim of this study was the evaluation of new serum biomarkers to be used individually or in combination, in order to improve the outcome of patients whose disease would be diagnosed at an earlier stage. Serum and plasma were available from 43 subjects previously exposed to asbestos and 27 MPM patients, all being epithelioid type. All the new markers found differentially expressed in MPM and healthy subjects, by proteomic and genomic approaches, have been validated in the serum by the use of specific ELISA. The combined approach, using tools of genomics and proteomics, is found to be highly innovative for this type of disease and led to the identification of new serum markers in the diagnosis of MPM. These results, if confirmed in a larger series, may have a strong impact in this area, because early detection of this cancer in people at high risk could significantly improve the course of the disease and the clinical approach to an individualized therapy.

  8. Comparative Genome Analysis and Genome Evolution

    NARCIS (Netherlands)

    Snel, Berend

    2002-01-01

    This thesis described a collection of bioinformatic analyses on complete genome sequence data. We have studied the evolution of gene content and find that vertical inheritance dominates over horizontal gene trasnfer, even to the extent that we can use the gene content to make genome phylogenies.

  9. Dietary and health biomarkers-time for an update

    NARCIS (Netherlands)

    Dragsted, L.O.; Gao Qizian,; Praticò, G.; Manach, Claudine; Wishart, D.S.; Scalbert, A.; Feskens, E.J.M.

    2017-01-01

    In the dietary and health research area, biomarkers are extensively used for multiple purposes. These include biomarkers of dietary intake and nutrient status, biomarkers used to measure the biological effects of specific dietary components, and biomarkers to assess the effects of diet on health.

  10. Potentials of single-cell biology in identification and validation of disease biomarkers.

    Science.gov (United States)

    Niu, Furong; Wang, Diane C; Lu, Jiapei; Wu, Wei; Wang, Xiangdong

    2016-09-01

    Single-cell biology is considered a new approach to identify and validate disease-specific biomarkers. However, the concern raised by clinicians is how to apply single-cell measurements for clinical practice, translate the message of single-cell systems biology into clinical phenotype or explain alterations of single-cell gene sequencing and function in patient response to therapies. This study is to address the importance and necessity of single-cell gene sequencing in the identification and development of disease-specific biomarkers, the definition and significance of single-cell biology and single-cell systems biology in the understanding of single-cell full picture, the development and establishment of whole-cell models in the validation of targeted biological function and the figure and meaning of single-molecule imaging in single cell to trace intra-single-cell molecule expression, signal, interaction and location. We headline the important role of single-cell biology in the discovery and development of disease-specific biomarkers with a special emphasis on understanding single-cell biological functions, e.g. mechanical phenotypes, single-cell biology, heterogeneity and organization of genome function. We have reason to believe that such multi-dimensional, multi-layer, multi-crossing and stereoscopic single-cell biology definitely benefits the discovery and development of disease-specific biomarkers. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  11. Genomic Data Commons launches

    Science.gov (United States)

    The Genomic Data Commons (GDC), a unified data system that promotes sharing of genomic and clinical data between researchers, launched today with a visit from Vice President Joe Biden to the operations center at the University of Chicago.

  12. Rat Genome Database (RGD)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Rat Genome Database (RGD) is a collaborative effort between leading research institutions involved in rat genetic and genomic research to collect, consolidate,...

  13. Visualization for genomics: the Microbial Genome Viewer.

    Science.gov (United States)

    Kerkhoven, Robert; van Enckevort, Frank H J; Boekhorst, Jos; Molenaar, Douwe; Siezen, Roland J

    2004-07-22

    A Web-based visualization tool, the Microbial Genome Viewer, is presented that allows the user to combine complex genomic data in a highly interactive way. This Web tool enables the interactive generation of chromosome wheels and linear genome maps from genome annotation data stored in a MySQL database. The generated images are in scalable vector graphics (SVG) format, which is suitable for creating high-quality scalable images and dynamic Web representations. Gene-related data such as transcriptome and time-course microarray experiments can be superimposed on the maps for visual inspection. The Microbial Genome Viewer 1.0 is freely available at http://www.cmbi.kun.nl/MGV

  14. Biomarker monitoring in sports doping control.

    Science.gov (United States)

    Pottgiesser, Torben; Schumacher, Yorck Olaf

    2012-06-01

    Biomarker monitoring can be considered a new era in the effort against doping. Opposed to the old concept in doping control of direct detection of a prohibited substance in a biological sample such as urine or blood, the new paradigm allows a personalized longitudinal monitoring of biomarkers that indicate non-physiological responses independently of the used doping technique or substance, and may cause sanctioning of illicit practices. This review presents the development of biomarker monitoring in sports doping control and focuses on the implementation of the Athlete Biological Passport as the current concept of the World Anti Doping Agency for the detection of blood doping (hematological module). The scope of the article extends to the description of novel biomarkers and future concepts of application.

  15. Cellular Models for Environmental Toxicant Biomarker Discovery

    National Research Council Canada - National Science Library

    Halverson, Kelly M; Lewsis, John A; Jackson, David A; Dennis, William; Brennan, Linda; Krakaner, Teresa

    2006-01-01

    ...) is the development of biomarkers of exposure, effect, and susceptibility. As exposure monitoring using environmental sampling equipment can be impractical and doesn't account for differences in individual responses, new methodologies must be sought...

  16. Radiation Biomarker Research Using Mass Spectrometry

    National Research Council Canada - National Science Library

    Bach, Stephan B; Hubert, Walter

    2007-01-01

    .... This review is intended to give an overview of mass spectrometry and its application to biological systems and biomarker discovery and how that might relate to relevant radiation dosimetry studies...

  17. The development and applications of biomarkers

    International Nuclear Information System (INIS)

    Normandy, J.; Peeters, J.

    1994-01-01

    This report is a compilation of submitted abstracts of scientific papers presented at the second Department of Energy-supported workshop on the use and applications of biomarkers held in Santa Fe, New Mexico, from April 26--29, 1994. The abstracts present a synopsis of the latest scientific developments in biomarker research and how these developments meet with the practical needs of the occupational physician as well as the industrial hygienist and the health physicist. In addition to considering the practical applications and potential benefits of this promising technology, the potential ethical and legal ramifications of using biomarkers to monitor workers are discussed. The abstracts further present insights on the present benefits that can be derived from using biomarkers as well as a perspective on what further research is required to fully meet the needs of the medical community

  18. International Team Identifies Biomarker for Scleroderma

    Science.gov (United States)

    ... Spotlight on Research International Team Identifies Biomarker for Scleroderma By Kirstie Saltsman, Ph.D. | May 5, 2014 ... molecule correlates with a more severe form of scleroderma, a chronic autoimmune disorder that involves the abnormal ...

  19. Biomarkers in psoriasis and psoriatic arthritis.

    Science.gov (United States)

    Villanova, Federica; Di Meglio, Paola; Nestle, Frank O

    2013-04-01

    Psoriasis is a common immune-mediated disease of the skin, which associates in 20-30% of patients with psoriatic arthritis (PsA). The immunopathogenesis of both conditions is not fully understood as it is the result of a complex interaction between genetic, environmental and immunological factors. At present there is no cure for psoriasis and there are no specific markers that can accurately predict disease progression and therapeutic response. Therefore, biomarkers for disease prognosis and response to treatment are urgently needed to help clinicians with objective indications to improve patient management and outcomes. Although many efforts have been made to identify psoriasis/PsA biomarkers none of them has yet been translated into routine clinical practice. In this review we summarise the different classes of possible biomarkers explored in psoriasis and PsA so far and discuss novel strategies for biomarker discovery.

  20. Novel Biomarker for Prognosis, Treatment Response

    Science.gov (United States)

    An NCI Cancer Currents blog about a study of a new type of cancer biomarker that measures the extent of chromosomal instability as a way to potentially predict patient prognosis and help guide cancer treatment choices.

  1. The development and applications of biomarkers

    Energy Technology Data Exchange (ETDEWEB)

    Normandy, J.; Peeters, J. [eds.

    1994-04-15

    This report is a compilation of submitted abstracts of scientific papers presented at the second Department of Energy-supported workshop on the use and applications of biomarkers held in Santa Fe, New Mexico, from April 26--29, 1994. The abstracts present a synopsis of the latest scientific developments in biomarker research and how these developments meet with the practical needs of the occupational physician as well as the industrial hygienist and the health physicist. In addition to considering the practical applications and potential benefits of this promising technology, the potential ethical and legal ramifications of using biomarkers to monitor workers are discussed. The abstracts further present insights on the present benefits that can be derived from using biomarkers as well as a perspective on what further research is required to fully meet the needs of the medical community.

  2. Genomic prediction using subsampling

    OpenAIRE

    Xavier, Alencar; Xu, Shizhong; Muir, William; Rainey, Katy Martin

    2017-01-01

    Background Genome-wide assisted selection is a critical tool for the?genetic improvement of plants and animals. Whole-genome regression models in Bayesian framework represent the main family of prediction methods. Fitting such models with a large number of observations involves a prohibitive computational burden. We propose the use of subsampling bootstrap Markov chain in genomic prediction. Such method consists of fitting whole-genome regression models by subsampling observations in each rou...

  3. Have biomarkers made their mark? A brief review of dental biomarkers

    Directory of Open Access Journals (Sweden)

    Mohammed Kaleem Sultan

    2014-01-01

    Full Text Available Biomarkers are substances that are released into the human body by tumor cells or by other cells in response to tumor. A high level of a tumor marker is considered a sign of certain cancer, which makes biomarker the subject of many testing methods for the diagnosis of cancers. In recent times, these biomarkers have been successfully isolated to diagnose dental-related tumors, benign and malignant conditions. This article is a brief review of literature for various biomarkers used in the field of dentistry.

  4. Salivary pH: A diagnostic biomarker

    OpenAIRE

    Baliga, Sharmila; Muglikar, Sangeeta; Kale, Rahul

    2013-01-01

    Objectives: Saliva contains a variety of host defense factors. It influences calculus formation and periodontal disease. Different studies have been done to find exact correlation of salivary biomarkers with periodontal disease. With a multitude of biomarkers and complexities in their determination, the salivary pH may be tried to be used as a quick chairside test. The aim of this study was to analyze the pH of saliva and determine its relevance to the severity of periodontal disease. Study D...

  5. Ebolavirus comparative genomics

    DEFF Research Database (Denmark)

    Jun, Se-Ran; Leuze, Michael R.; Nookaew, Intawat

    2015-01-01

    The 2014 Ebola outbreak in West Africa is the largest documented for this virus. To examine the dynamics of this genome, we compare more than 100 currently available ebolavirus genomes to each other and to other viral genomes. Based on oligomer frequency analysis, the family Filoviridae forms...

  6. Quality assurance in biomarker measurement.

    Science.gov (United States)

    Aitio, A; Apostoli, P

    1995-05-01

    Quality assurance (QA) concerns the validity of all the analytical processes (from collection of the samples to interpretation of the results). It is not an abstract concept but must be adapted to the different situations such as the different exposure levels, the different analytical methods, and the context of use (risk assessment procedures, research, routine determinations). The main requirements in QA programmes regard the control of all the known sources of preanalytical and analytical variations, while the instruments with which adequate QA can be implemented are the certified materials and the quality control programmes (quality manual, internal and external quality controls). Another important concept in QA is that measurements must be placed a different metrological levels: at the highest there are the methods (definitive, reference) to be used for assessing accuracy of routine methods. QA programmes should enable a grading of biomarkers (from experimental only to full evaluated) and of the laboratories in order to identify the significance of the test and to assess the level at which a laboratory could operate.

  7. Shotgun Proteomics and Biomarker Discovery

    Directory of Open Access Journals (Sweden)

    W. Hayes McDonald

    2002-01-01

    Full Text Available Coupling large-scale sequencing projects with the amino acid sequence information that can be gleaned from tandem mass spectrometry (MS/MS has made it much easier to analyze complex mixtures of proteins. The limits of this “shotgun” approach, in which the protein mixture is proteolytically digested before separation, can be further expanded by separating the resulting mixture of peptides prior to MS/MS analysis. Both single dimensional high pressure liquid chromatography (LC and multidimensional LC (LC/LC can be directly interfaced with the mass spectrometer to allow for automated collection of tremendous quantities of data. While there is no single technique that addresses all proteomic challenges, the shotgun approaches, especially LC/LC-MS/MS-based techniques such as MudPIT (multidimensional protein identification technology, show advantages over gel-based techniques in speed, sensitivity, scope of analysis, and dynamic range. Advances in the ability to quantitate differences between samples and to detect for an array of post-translational modifications allow for the discovery of classes of protein biomarkers that were previously unassailable.

  8. Crevicular fluid biomarkers and periodontal disease progression.

    Science.gov (United States)

    Kinney, Janet S; Morelli, Thiago; Oh, Min; Braun, Thomas M; Ramseier, Christoph A; Sugai, Jim V; Giannobile, William V

    2014-02-01

    Assess the ability of a panel of gingival crevicular fluid (GCF) biomarkers as predictors of periodontal disease progression (PDP). In this study, 100 individuals participated in a 12-month longitudinal investigation and were categorized into four groups according to their periodontal status. GCF, clinical parameters and saliva were collected bi-monthly. Subgingival plaque and serum were collected bi-annually. For 6 months, no periodontal treatment was provided. At 6 months, patients received periodontal therapy and continued participation from 6 to 12 months. GCF samples were analysed by ELISA for MMP-8, MMP-9, Osteoprotegerin, C-reactive Protein and IL-1β. Differences in median levels of GCF biomarkers were compared between stable and progressing participants using Wilcoxon Rank Sum test (p = 0.05). Clustering algorithm was used to evaluate the ability of oral biomarkers to classify patients as either stable or progressing. Eighty-three individuals completed the 6-month monitoring phase. With the exception of GCF C-reactive protein, all biomarkers were significantly higher in the PDP group compared to stable patients. Clustering analysis showed highest sensitivity levels when biofilm pathogens and GCF biomarkers were combined with clinical measures, 74% (95% CI = 61, 86). Signature of GCF fluid-derived biomarkers combined with pathogens and clinical measures provides a sensitive measure for discrimination of PDP (ClinicalTrials.gov NCT00277745). © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Biomarkers in T cell therapy clinical trials

    Directory of Open Access Journals (Sweden)

    Kalos Michael

    2011-08-01

    Full Text Available Abstract T cell therapy represents an emerging and promising modality for the treatment of both infectious disease and cancer. Data from recent clinical trials have highlighted the potential for this therapeutic modality to effect potent anti-tumor activity. Biomarkers, operationally defined as biological parameters measured from patients that provide information about treatment impact, play a central role in the development of novel therapeutic agents. In the absence of information about primary clinical endpoints, biomarkers can provide critical insights that allow investigators to guide the clinical development of the candidate product. In the context of cell therapy trials, the definition of biomarkers can be extended to include a description of parameters of the cell product that are important for product bioactivity. This review will focus on biomarker studies as they relate to T cell therapy trials, and more specifically: i. An overview and description of categories and classes of biomarkers that are specifically relevant to T cell therapy trials, and ii. Insights into future directions and challenges for the appropriate development of biomarkers to evaluate both product bioactivity and treatment efficacy of T cell therapy trials.

  10. Análise da associação entre índices de risco ao desenvolvimento infantil e produção inicial de fala entre 13 e 16 meses

    Directory of Open Access Journals (Sweden)

    Anelise Henrich Crestani

    2015-02-01

    Full Text Available OBJETIVOS: investigar a associação entre presença de risco ao desenvolvimento infantil e produção inicial de fala de crianças na faixa de 13 a 16 meses de idade e analisar o valor preditivo dos índices de risco ao desenvolvimento infantil em relação à aquisição inicial da linguagem. MÉTODOS: a amostra foi constituída de 52 díades mães-bebês, seguidas em estudo de coorte de zero aos 18 meses, por meio dos Índices de risco ao desenvolvimento infantil e avaliadas quanto à produção de fala entre 13 e 16 meses por meio de lembranças espontâneas das mães e da observação do comportamento infantil. Os dados foram organizados em categorias e lançados para a análise estatística no aplicativo computacional STATISTICA 9.0. RESULTADOS: a aquisição da linguagem inicial, medida pelo número de palavras faladas pelo bebê, difere de modo significante na presença de riscos ao desenvolvimento na primeira fase (0 - 4 meses e considerando bebês que apresentaram risco em alguma das quatro fases (0 - 18 meses, visto que bebês com risco apresentam número de produção de vocábulos estatisticamente inferior em relação aos sem risco. CONCLUSÃO: pela análise dos resultados a pesquisa demonstrou associação estatística entre risco ao desenvolvimento infantil e produção inicial de fala. Quanto maior o risco menor a produção de fala.

  11. The Sequenced Angiosperm Genomes and Genome Databases.

    Science.gov (United States)

    Chen, Fei; Dong, Wei; Zhang, Jiawei; Guo, Xinyue; Chen, Junhao; Wang, Zhengjia; Lin, Zhenguo; Tang, Haibao; Zhang, Liangsheng

    2018-01-01

    Angiosperms, the flowering plants, provide the essential resources for human life, such as food, energy, oxygen, and materials. They also promoted the evolution of human, animals, and the planet earth. Despite the numerous advances in genome reports or sequencing technologies, no review covers all the released angiosperm genomes and the genome databases for data sharing. Based on the rapid advances and innovations in the database reconstruction in the last few years, here we provide a comprehensive review for three major types of angiosperm genome databases, including databases for a single species, for a specific angiosperm clade, and for multiple angiosperm species. The scope, tools, and data of each type of databases and their features are concisely discussed. The genome databases for a single species or a clade of species are especially popular for specific group of researchers, while a timely-updated comprehensive database is more powerful for address of major scientific mysteries at the genome scale. Considering the low coverage of flowering plants in any available database, we propose construction of a comprehensive database to facilitate large-scale comparative studies of angiosperm genomes and to promote the collaborative studies of important questions in plant biology.

  12. Biomarkers of exposure, effect, and susceptibility of arsenic-induced health hazards in Taiwan

    International Nuclear Information System (INIS)

    Chen, C.-J.; Hsu, L.-I; Wang, C.-H.

    2005-01-01

    Long-term exposure to inorganic arsenic from drinking water has been documented to induce cancers and vascular diseases in a dose-response relationship. A series of molecular environmental epidemiological studies have been carried out to elucidate biomarkers of exposure, effect, and susceptibility for arsenic-related health hazards in Taiwan. Arsenic levels in urine, hair, and nail are biomarkers for short-term (<1 year) internal dose, skin hyperpigmentation and palmoplantar hyperkeratosis are for long-term (many years) internal dose, and percentage of monomethylarsonic acid in total metabolites of inorganic arsenic in urine may be considered as an exposure marker for biologically effective dose. The biomarkers of early biological effects of ingested inorganic arsenic included blood levels of reactive oxidants and anti-oxidant capacity, genetic expression of inflammatory molecules, as well as cytogenetic changes including sister chromatid exchange, micronuclei, and chromosome aberrations of peripheral lymphocytes. Both mutation type and hot spots of p53 gene were significantly different in arsenic-induced and non-arsenic-induced TCCs. The frequency of chromosomal imbalances analyzed by comparative genomic hybridization and the frequency of loss of heterozygosity were significantly higher in arsenic-induced TCC than non-arsenic-induced TCC at specific sites. Biomarkers of susceptibility to arsenic-induced health hazards included genetic polymorphisms of enzymes involved in xenobiotic metabolism, DNA repair, and oxidative stress, as well as serum level of carotenoids. Gene-gene and gene-environment interactions are involved in arsenic-induced health hazards through toxicological mechanisms including genomic instability and oxidative stress

  13. Genome sequencing elucidates Sardinian genetic architecture and augments association analyses for lipid and blood inflammatory markers

    Science.gov (United States)

    Zoledziewska, Magdalena; Mulas, Antonella; Pistis, Giorgio; Steri, Maristella; Danjou, Fabrice; Kwong, Alan; Ortega del Vecchyo, Vicente Diego; Chiang, Charleston W. K.; Bragg-Gresham, Jennifer; Pitzalis, Maristella; Nagaraja, Ramaiah; Tarrier, Brendan; Brennan, Christine; Uzzau, Sergio; Fuchsberger, Christian; Atzeni, Rossano; Reinier, Frederic; Berutti, Riccardo; Huang, Jie; Timpson, Nicholas J; Toniolo, Daniela; Gasparini, Paolo; Malerba, Giovanni; Dedoussis, George; Zeggini, Eleftheria; Soranzo, Nicole; Jones, Chris; Lyons, Robert; Angius, Andrea; Kang, Hyun M.; Novembre, John; Sanna, Serena; Schlessinger, David; Cucca, Francesco; Abecasis, Gonçalo R

    2015-01-01

    We report ~17.6M genetic variants from whole-genome sequencing of 2,120 Sardinians; 22% are absent from prior sequencing-based compilations and enriched for predicted functional consequence. Furthermore, ~76K variants common in our sample (frequency >5%) are rare elsewhere (Genomes Project). We assessed the impact of these variants on circulating lipid levels and five inflammatory biomarkers. Fourteen signals, including two major new loci, were observed for lipid levels, and 19, including two novel loci, for inflammatory markers. New associations would be missed in analyses based on 1000 Genomes data, underlining the advantages of large-scale sequencing in this founder population. PMID:26366554

  14. Potential Impact on Clinical Decision Making via a Genome-Wide Expression Profiling: A Case Report

    Directory of Open Access Journals (Sweden)

    Hyun Kim

    2016-11-01

    Full Text Available Management of men with prostate cancer is fraught with uncertainty as physicians and patients balance efficacy with potential toxicity and diminished quality of life. Utilization of genomics as a prognostic biomarker has improved the informed decision-making process by enabling more rationale treatment choices. Recently investigations have begun to determine whether genomic information from tumor transcriptome data can be used to impact clinical decision-making beyond prognosis. Here we discuss the potential of genomics to alter management of a patient who presented with high-risk prostate adenocarcinoma. We suggest that this information help selecting patients for advanced imaging, chemotherapies, or clinical trial.

  15. Biomarkers, Natural Course and Prognosis.

    Science.gov (United States)

    Arenillas, Juan F; López-Cancio, Elena; Wong, Ka Sing

    2016-01-01

    Increasing our knowledge about intracranial atherosclerosis (ICAS) natural history and prognostic factors is essential to improve its preventive therapy and thus reduce the dramatic clinical consequences caused by this entity. ICAS is characterized by a chronic and progressive course until it becomes symptomatic, mostly through complication of an unstable intracranial atherosclerotic plaque. Population-based studies in healthy subjects have shown that the prevalence of asymptomatic ICAS is higher in Asian than in Caucasian populations. In both settings, asymptomatic ICAS is associated with classical vascular risk factors and with the metabolic syndrome, and it is burdened with an increasing risk of having incident stroke and cognitive impairment. When it reaches its symptomatic stage, ICAS is a dynamic and aggressive condition, and affected patients are at high risk of having recurrent stroke and other major vascular events. The Stenting versus Aggressive Medical Therapy for Intracranial Arterial Stenosis (SAMMPRIS) trial has recently shown a robust impact of intensive medical therapy reducing the risk of clinical recurrence of symptomatic ICAS. However, even under best medical therapy and degree of risk factor control, symptomatic ICAS-related recurrence risk continues to be the highest among all stroke etiologic subtypes. The second part of the chapter reviews the current understanding of prognostic factors that may help discriminate the high-risk ICAS patients, divided into local factors (vulnerable ICAS plaque) and systemic factors (vulnerable ICAS patient). Regarding research on local factors, high-resolution magnetic resonance imaging (HRMRI) is an emerging technique that allows in vivo evaluation of intracranial arterial wall, which is displacing our research focus from intracranial stenosis degree towards intracranial atherosclerotic plaque composition and activity. Characterization of the vulnerable ICAS patient may be improved with biomarker research. The

  16. Genome-wide comparison of medieval and modern Mycobacterium leprae.

    Science.gov (United States)

    Schuenemann, Verena J; Singh, Pushpendra; Mendum, Thomas A; Krause-Kyora, Ben; Jäger, Günter; Bos, Kirsten I; Herbig, Alexander; Economou, Christos; Benjak, Andrej; Busso, Philippe; Nebel, Almut; Boldsen, Jesper L; Kjellström, Anna; Wu, Huihai; Stewart, Graham R; Taylor, G Michael; Bauer, Peter; Lee, Oona Y-C; Wu, Houdini H T; Minnikin, David E; Besra, Gurdyal S; Tucker, Katie; Roffey, Simon; Sow, Samba O; Cole, Stewart T; Nieselt, Kay; Krause, Johannes

    2013-07-12

    Leprosy was endemic in Europe until the Middle Ages. Using DNA array capture, we have obtained genome sequences of Mycobacterium leprae from skeletons of five medieval leprosy cases from the United Kingdom, Sweden, and Denmark. In one case, the DNA was so well preserved that full de novo assembly of the ancient bacterial genome could be achieved through shotgun sequencing alone. The ancient M. leprae sequences were compared with those of 11 modern strains, representing diverse genotypes and geographic origins. The comparisons revealed remarkable genomic conservation during the past 1000 years, a European origin for leprosy in the Americas, and the presence of an M. leprae genotype in medieval Europe now commonly associated with the Middle East. The exceptional preservation of M. leprae biomarkers, both DNA and mycolic acids, in ancient skeletons has major implications for palaeomicrobiology and human pathogen evolution.

  17. Protein biomarker enrichment by biomarker antibody complex elution for immunoassay biosensing

    NARCIS (Netherlands)

    Sabatté, G.S.; Feitsma, H.; Evers, T.H.; Prins, M.W.J.

    2011-01-01

    It is very challenging to perform sample enrichment for protein biomarkers because proteins can easily change conformation and denature. In this paper we demonstrate protein enrichment suited for high-sensitivity integrated immuno-biosensing. The method enhances the concentration of the biomarkers

  18. Validation of biomarkers of food intake − critical assessment of candidate biomarkers

    DEFF Research Database (Denmark)

    Dragsted, Lars Ove; Gao, Qian; Scalbert, Augustin

    2018-01-01

    Biomarkers of food intake (BFIs) are a promising tool for limiting misclassification in nutrition research where more subjective dietary assessment instruments are used. They may also be used to assess compliance to dietary guidelines or to a dietary intervention. Biomarkers therefore hold promis...

  19. Dietary and health biomarkers - time for an update

    DEFF Research Database (Denmark)

    Dragsted, Lars Ove; Gao, Qian; Pratico, Giulia

    2017-01-01

    for these biomarker classes, and no recent systematic review of all proposed biomarkers for food intake. While advanced databases exist for the human and food metabolomes, additional tools are needed to curate and evaluate current data on dietary and health biomarkers. The Food Biomarkers Alliance (FoodBAll) under......In the dietary and health research area, biomarkers are extensively used for multiple purposes. These include biomarkers of dietary intake and nutrient status, biomarkers used to measure the biological effects of specific dietary components, and biomarkers to assess the effects of diet on health...... much mechanistic insight into the effects of food components and diets. Although hundreds of papers in nutrition are published annually, there is no current ontology for the area, no generally accepted classification terminology for biomarkers in nutrition and health, no systematic validation scheme...

  20. Prostate Cancer Imaging and Biomarkers Guiding Safe Selection of Active Surveillance

    Directory of Open Access Journals (Sweden)

    Zachary A. Glaser

    2017-10-01

    Full Text Available BackgroundActive surveillance (AS is a widely adopted strategy to monitor men with low-risk, localized prostate cancer (PCa. Current AS inclusion criteria may misclassify as many as one in four patients. The advent of multiparametric magnetic resonance imaging (mpMRI and novel PCa biomarkers may offer improved risk stratification. We performed a review of recently published literature to characterize emerging evidence in support of these novel modalities.MethodsAn English literature search was conducted on PubMed for available original investigations on localized PCa, AS, imaging, and biomarkers published within the past 3 years. Our Boolean criteria included the following terms: PCa, AS, imaging, biomarker, genetic, genomic, prospective, retrospective, and comparative. The bibliographies and diagnostic modalities of the identified studies were used to expand our search.ResultsOur review identified 222 original studies. Our expanded search yielded 244 studies. Among these, 70 met our inclusion criteria. Evidence suggests mpMRI offers improved detection of clinically significant PCa, and MRI-fusion technology enhances the sensitivity of surveillance biopsies. Multiple studies demonstrate the promise of commercially available screening assays for prediction of AS failure, and several novel biomarkers show promise in this setting.ConclusionIn the era of AS for men with low-risk PCa, improved strategies for proper stratification are needed. mpMRI has dramatically enhanced the detection of clinically significant PCa. The advent of novel biomarkers for prediction of aggressive disease and AS failure has shown some initial promise, but further validation is warranted.

  1. Comprehensive Analysis of Cancer-Proteogenome to Identify Biomarkers for the Early Diagnosis and Prognosis of Cancer.

    Science.gov (United States)

    Shukla, Hem D

    2017-10-25

    During the past century, our understanding of cancer diagnosis and treatment has been based on a monogenic approach, and as a consequence our knowledge of the clinical genetic underpinnings of cancer is incomplete. Since the completion of the human genome in 2003, it has steered us into therapeutic target discovery, enabling us to mine the genome using cutting edge proteogenomics tools. A number of novel and promising cancer targets have emerged from the genome project for diagnostics, therapeutics, and prognostic markers, which are being used to monitor response to cancer treatment. The heterogeneous nature of cancer has hindered progress in understanding the underlying mechanisms that lead to abnormal cellular growth. Since, the start of The Cancer Genome Atlas (TCGA), and the International Genome consortium projects, there has been tremendous progress in genome sequencing and immense numbers of cancer genomes have been completed, and this approach has transformed our understanding of the diagnosis and treatment of different types of cancers. By employing Genomics and proteomics technologies, an immense amount of genomic data is being generated on clinical tumors, which has transformed the cancer landscape and has the potential to transform cancer diagnosis and prognosis. A complete molecular view of the cancer landscape is necessary for understanding the underlying mechanisms of cancer initiation to improve diagnosis and prognosis, which ultimately will lead to personalized treatment. Interestingly, cancer proteome analysis has also allowed us to identify biomarkers to monitor drug and radiation resistance in patients undergoing cancer treatment. Further, TCGA-funded studies have allowed for the genomic and transcriptomic characterization of targeted cancers, this analysis aiding the development of targeted therapies for highly lethal malignancy. High-throughput technologies, such as complete proteome, epigenome, protein-protein interaction, and pharmacogenomics

  2. Comprehensive Analysis of Cancer-Proteogenome to Identify Biomarkers for the Early Diagnosis and Prognosis of Cancer

    Directory of Open Access Journals (Sweden)

    Hem D. Shukla

    2017-10-01

    Full Text Available During the past century, our understanding of cancer diagnosis and treatment has been based on a monogenic approach, and as a consequence our knowledge of the clinical genetic underpinnings of cancer is incomplete. Since the completion of the human genome in 2003, it has steered us into therapeutic target discovery, enabling us to mine the genome using cutting edge proteogenomics tools. A number of novel and promising cancer targets have emerged from the genome project for diagnostics, therapeutics, and prognostic markers, which are being used to monitor response to cancer treatment. The heterogeneous nature of cancer has hindered progress in understanding the underlying mechanisms that lead to abnormal cellular growth. Since, the start of The Cancer Genome Atlas (TCGA, and the International Genome consortium projects, there has been tremendous progress in genome sequencing and immense numbers of cancer genomes have been completed, and this approach has transformed our understanding of the diagnosis and treatment of different types of cancers. By employing Genomics and proteomics technologies, an immense amount of genomic data is being generated on clinical tumors, which has transformed the cancer landscape and has the potential to transform cancer diagnosis and prognosis. A complete molecular view of the cancer landscape is necessary for understanding the underlying mechanisms of cancer initiation to improve diagnosis and prognosis, which ultimately will lead to personalized treatment. Interestingly, cancer proteome analysis has also allowed us to identify biomarkers to monitor drug and radiation resistance in patients undergoing cancer treatment. Further, TCGA-funded studies have allowed for the genomic and transcriptomic characterization of targeted cancers, this analysis aiding the development of targeted therapies for highly lethal malignancy. High-throughput technologies, such as complete proteome, epigenome, protein–protein interaction

  3. Bioinformatics decoding the genome

    CERN Multimedia

    CERN. Geneva; Deutsch, Sam; Michielin, Olivier; Thomas, Arthur; Descombes, Patrick

    2006-01-01

    Extracting the fundamental genomic sequence from the DNA From Genome to Sequence : Biology in the early 21st century has been radically transformed by the availability of the full genome sequences of an ever increasing number of life forms, from bacteria to major crop plants and to humans. The lecture will concentrate on the computational challenges associated with the production, storage and analysis of genome sequence data, with an emphasis on mammalian genomes. The quality and usability of genome sequences is increasingly conditioned by the careful integration of strategies for data collection and computational analysis, from the construction of maps and libraries to the assembly of raw data into sequence contigs and chromosome-sized scaffolds. Once the sequence is assembled, a major challenge is the mapping of biologically relevant information onto this sequence: promoters, introns and exons of protein-encoding genes, regulatory elements, functional RNAs, pseudogenes, transposons, etc. The methodological ...

  4. Genomic research in Eucalyptus.

    Science.gov (United States)

    Poke, Fiona S; Vaillancourt, René E; Potts, Brad M; Reid, James B

    2005-09-01

    Eucalyptus L'Hérit. is a genus comprised of more than 700 species that is of vital importance ecologically to Australia and to the forestry industry world-wide, being grown in plantations for the production of solid wood products as well as pulp for paper. With the sequencing of the genomes of Arabidopsis thaliana and Oryza sativa and the recent completion of the first tree genome sequence, Populus trichocarpa, attention has turned to the current status of genomic research in Eucalyptus. For several eucalypt species, large segregating families have been established, high-resolution genetic maps constructed and large EST databases generated. Collaborative efforts have been initiated for the integration of diverse genomic projects and will provide the framework for future research including exploiting the sequence of the entire eucalypt genome which is currently being sequenced. This review summarises the current position of genomic research in Eucalyptus and discusses the direction of future research.

  5. Nanomaterials based biosensors for cancer biomarker detection

    International Nuclear Information System (INIS)

    Malhotra, Bansi D; Kumar, Saurabh; Pandey, Chandra Mouli

    2016-01-01

    Biosensors have enormous potential to contribute to the evolution of new molecular diagnostic techniques for patients suffering with cancerous diseases. A major obstacle preventing faster development of biosensors pertains to the fact that cancer is a highly complex set of diseases. The oncologists currently rely on a few biomarkers and histological characterization of tumors. Some of the signatures include epigenetic and genetic markers, protein profiles, changes in gene expression, and post-translational modifications of proteins. These molecular signatures offer new opportunities for development of biosensors for cancer detection. In this context, conducting paper has recently been found to play an important role towards the fabrication of a biosensor for cancer biomarker detection. In this paper we will focus on results of some of the recent studies obtained in our laboratories relating to fabrication and application of nanomaterial modified paper based biosensors for cancer biomarker detection. (paper)

  6. Using Aptamers for Cancer Biomarker Discovery

    Directory of Open Access Journals (Sweden)

    Yun Min Chang

    2013-01-01

    Full Text Available Aptamers are single-stranded synthetic DNA- or RNA-based oligonucleotides that fold into various shapes to bind to a specific target, which includes proteins, metals, and molecules. Aptamers have high affinity and high specificity that are comparable to that of antibodies. They are obtained using iterative method, called (Systematic Evolution of Ligands by Exponential Enrichment SELEX and cell-based SELEX (cell-SELEX. Aptamers can be paired with recent advances in nanotechnology, microarray, microfluidics, and other technologies for applications in clinical medicine. One particular area that aptamers can shed a light on is biomarker discovery. Biomarkers are important in diagnosis and treatment of cancer. In this paper, we will describe ways in which aptamers can be used to discover biomarkers for cancer diagnosis and therapeutics.

  7. Biomarkers in pancreatic adenocarcinoma: current perspectives.

    Science.gov (United States)

    Swords, Douglas S; Firpo, Matthew A; Scaife, Courtney L; Mulvihill, Sean J

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year survival rate of 7.7%. Most patients are diagnosed at an advanced stage not amenable to potentially curative resection. A substantial portion of this review is dedicated to reviewing the current literature on carbohydrate antigen (CA 19-9), which is currently the only guideline-recommended biomarker for PDAC. It provides valuable prognostic information, can predict resectability, and is useful in decision making about neoadjuvant therapy. We also discuss carcinoembryonic antigen (CEA), CA 125, serum biomarker panels, circulating tumor cells, and cell-free nucleic acids. Although many biomarkers have now been studied in relation to PDAC, significant work still needs to be done to validate their usefulness in the early detection of PDAC and management of patients with PDAC.

  8. Biomarkers in the evolution of multiple sclerosis.

    Science.gov (United States)

    Berger, Thomas

    2017-11-01

    Nonimaging biomarkers can be applied in differential diagnosis, evaluation of disease progression and therapy monitoring of multiple sclerosis (MS). Presence of oligoclonal IgG bands in cerebrospinal fluid is a diagnostic element and a negative predictor of MS evolution. AQP4 antibodies are pathogenic and diagnostic for neuromyelitis optica spectrum disorder. Antibodies to myelin oligodendrocyte glycoprotein develop in about 50% of predominantly pediatric patients with acute disseminated encephalomyelitis, but their possible role in pathogenesis is unknown. Currently, there are no individualized biomarkers suitable to track disease progression. Neutralizing antibodies against IFN-β, natalizumab and daclizumab arise with variable frequency and reduce treatment efficacy. The anti-John Cunningham virus antibody index has potential as a biomarker for risk of progressive multifocal leukoencephalopathy.

  9. Other biomarkers for detecting prostate cancer.

    Science.gov (United States)

    Nogueira, Lucas; Corradi, Renato; Eastham, James A

    2010-01-01

    Prostate-specific antigen (PSA) has been used for detecting prostate cancer since 1994. Although it is the best cancer biomarker available, PSA is not perfect. It lacks both the sensitivity and specificity to accurately detect the presence of prostate cancer. None of the PSA thresholds currently in use consistently identify patients with prostate cancer and exclude patients without cancer. Novel approaches to improve our ability to detect prostate cancer and predict the course of the disease are needed. Additional methods for detecting prostate cancer have been evaluated. Despite the discovery of many new biomarkers, only a few have shown some clinical value. These markers include human kallikrein 2, urokinase-type plasminogen activator receptor, prostate-specific membrane antigen, early prostate cancer antigen, PCA3, alpha-methylacyl-CoA racemase and glutathione S-transferase pi hypermethylation. We review the reports on biomarkers for prostate cancer detection, and their possible role in the clinical practice.

  10. Molecular biomarkers in idiopathic pulmonary fibrosis

    Science.gov (United States)

    Ley, Brett; Brown, Kevin K.

    2014-01-01

    Molecular biomarkers are highly desired in idiopathic pulmonary fibrosis (IPF), where they hold the potential to elucidate underlying disease mechanisms, accelerated drug development, and advance clinical management. Currently, there are no molecular biomarkers in widespread clinical use for IPF, and the search for potential markers remains in its infancy. Proposed core mechanisms in the pathogenesis of IPF for which candidate markers have been offered include alveolar epithelial cell dysfunction, immune dysregulation, and fibrogenesis. Useful markers reflect important pathological pathways, are practically and accurately measured, have undergone extensive validation, and are an improvement upon the current approach for their intended use. The successful development of useful molecular biomarkers is a central challenge for the future of translational research in IPF and will require collaborative efforts among those parties invested in advancing the care of patients with IPF. PMID:25260757

  11. Biomarkers for CNS involvement in pediatric lupus

    Science.gov (United States)

    Rubinstein, Tamar B; Putterman, Chaim; Goilav, Beatrice

    2015-01-01

    CNS disease, or central neuropsychiatric lupus erythematosus (cNPSLE), occurs frequently in pediatric lupus, leading to significant morbidity and poor long-term outcomes. Diagnosing cNPSLE is especially difficult in pediatrics; many current diagnostic tools are invasive and/or costly, and there are no current accepted screening mechanisms. The most complicated aspect of diagnosis is differentiating primary disease from other etiologies; research to discover new biomarkers is attempting to address this dilemma. With many mechanisms involved in the pathogenesis of cNPSLE, biomarker profiles across several modalities (molecular, psychometric and neuroimaging) will need to be used. For the care of children with lupus, the challenge will be to develop biomarkers that are accessible by noninvasive measures and reliable in a pediatric population. PMID:26079959

  12. Emerging biomarkers for cancer immunotherapy in melanoma.

    Science.gov (United States)

    Axelrod, Margaret L; Johnson, Douglas B; Balko, Justin M

    2017-09-14

    The treatment and prognosis of metastatic melanoma has changed substantially since the advent of novel immune checkpoint inhibitors (ICI), agents that enhance the anti-tumor immune response. Despite the success of these agents, clinically actionable biomarkers to aid patient and regimen selection are lacking. Herein, we summarize and review the evidence for candidate biomarkers of response to ICIs in melanoma. Many of these candidates can be examined as parts of a known molecular pathway of immune response, while others are clinical in nature. Due to the ability of ICIs to illicit dramatic and durable responses, well-validated biomarkers that can be effectively implemented in the clinic will require strong negative predictive values that do not limit patients with who may benefit from ICI therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Genome packaging in viruses

    OpenAIRE

    Sun, Siyang; Rao, Venigalla B.; Rossmann, Michael G.

    2010-01-01

    Genome packaging is a fundamental process in a viral life cycle. Many viruses assemble preformed capsids into which the genomic material is subsequently packaged. These viruses use a packaging motor protein that is driven by the hydrolysis of ATP to condense the nucleic acids into a confined space. How these motor proteins package viral genomes had been poorly understood until recently, when a few X-ray crystal structures and cryo-electron microscopy structures became available. Here we discu...

  14. Between Two Fern Genomes

    Science.gov (United States)

    2014-01-01

    Ferns are the only major lineage of vascular plants not represented by a sequenced nuclear genome. This lack of genome sequence information significantly impedes our ability to understand and reconstruct genome evolution not only in ferns, but across all land plants. Azolla and Ceratopteris are ideal and complementary candidates to be the first ferns to have their nuclear genomes sequenced. They differ dramatically in genome size, life history, and habit, and thus represent the immense diversity of extant ferns. Together, this pair of genomes will facilitate myriad large-scale comparative analyses across ferns and all land plants. Here we review the unique biological characteristics of ferns and describe a number of outstanding questions in plant biology that will benefit from the addition of ferns to the set of taxa with sequenced nuclear genomes. We explain why the fern clade is pivotal for understanding genome evolution across land plants, and we provide a rationale for how knowledge of fern genomes will enable progress in research beyond the ferns themselves. PMID:25324969

  15. Causes of genome instability

    DEFF Research Database (Denmark)

    Langie, Sabine A S; Koppen, Gudrun; Desaulniers, Daniel

    2015-01-01

    function, chromosome segregation, telomere length). The purpose of this review is to describe the crucial aspects of genome instability, to outline the ways in which environmental chemicals can affect this cancer hallmark and to identify candidate chemicals for further study. The overall aim is to make......Genome instability is a prerequisite for the development of cancer. It occurs when genome maintenance systems fail to safeguard the genome's integrity, whether as a consequence of inherited defects or induced via exposure to environmental agents (chemicals, biological agents and radiation). Thus...

  16. Fungal Genomics Program

    Energy Technology Data Exchange (ETDEWEB)

    Grigoriev, Igor

    2012-03-12

    The JGI Fungal Genomics Program aims to scale up sequencing and analysis of fungal genomes to explore the diversity of fungi important for energy and the environment, and to promote functional studies on a system level. Combining new sequencing technologies and comparative genomics tools, JGI is now leading the world in fungal genome sequencing and analysis. Over 120 sequenced fungal genomes with analytical tools are available via MycoCosm (www.jgi.doe.gov/fungi), a web-portal for fungal biologists. Our model of interacting with user communities, unique among other sequencing centers, helps organize these communities, improves genome annotation and analysis work, and facilitates new larger-scale genomic projects. This resulted in 20 high-profile papers published in 2011 alone and contributing to the Genomics Encyclopedia of Fungi, which targets fungi related to plant health (symbionts, pathogens, and biocontrol agents) and biorefinery processes (cellulose degradation, sugar fermentation, industrial hosts). Our next grand challenges include larger scale exploration of fungal diversity (1000 fungal genomes), developing molecular tools for DOE-relevant model organisms, and analysis of complex systems and metagenomes.

  17. MIPS plant genome information resources.

    Science.gov (United States)

    Spannagl, Manuel; Haberer, Georg; Ernst, Rebecca; Schoof, Heiko; Mayer, Klaus F X

    2007-01-01

    The Munich Institute for Protein Sequences (MIPS) has been involved in maintaining plant genome databases since the Arabidopsis thaliana genome project. Genome databases and analysis resources have focused on individual genomes and aim to provide flexible and maintainable data sets for model plant genomes as a backbone against which experimental data, for example from high-throughput functional genomics, can be organized and evaluated. In addition, model genomes also form a scaffold for comparative genomics, and much can be learned from genome-wide evolutionary studies.

  18. Biomarkers and Targeted Therapy in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Fataneh Karandish

    2016-01-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC constitutes 90% of pancreatic cancers. PDAC is a complex and devastating disease with only 1%–3% survival rate in five years after the second stage. Treatment of PDAC is complicated due to the tumor microenvironment, changing cell behaviors to the mesenchymal type, altered drug delivery, and drug resistance. Considering that pancreatic cancer shows early invasion and metastasis, critical research is needed to explore different aspects of the disease, such as elaboration of biomarkers, specific signaling pathways, and gene aberration. In this review, we highlight the biomarkers, the fundamental signaling pathways, and their importance in targeted drug delivery for pancreatic cancers.

  19. Biomarkers and Targeted Therapy in Pancreatic Cancer.

    Science.gov (United States)

    Karandish, Fataneh; Mallik, Sanku

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) constitutes 90% of pancreatic cancers. PDAC is a complex and devastating disease with only 1%-3% survival rate in five years after the second stage. Treatment of PDAC is complicated due to the tumor microenvironment, changing cell behaviors to the mesenchymal type, altered drug delivery, and drug resistance. Considering that pancreatic cancer shows early invasion and metastasis, critical research is needed to explore different aspects of the disease, such as elaboration of biomarkers, specific signaling pathways, and gene aberration. In this review, we highlight the biomarkers, the fundamental signaling pathways, and their importance in targeted drug delivery for pancreatic cancers.

  20. Biomarkers of multiorgan injury in neonatal encephalopathy.

    Science.gov (United States)

    Aslam, Saima; Molloy, Eleanor J

    2015-01-01

    Neonatal encephalopathy (NE) is a major contributor to neurodevelopmental deficits including cerebral palsy in term and near-term infants. The long-term neurodevelopmental outcome is difficult to predict with certainty in first few days of life. Multiorgan involvement is common but not part of the diagnostic criteria for NE. The most frequently involved organs are the heart, liver, kidneys and hematological system. Cerebral and organ involvement is associated with the release of organ specific biomarkers in cerebrospinal fluid, urine and blood. These biomarkers may have a role in the assessment of the severity of asphyxia and long-term outcome in neonates with NE.

  1. Biomarkers of necrotising soft tissue infections

    DEFF Research Database (Denmark)

    Hansen, Marco Bo; Simonsen, Ulf; Garred, Peter

    2015-01-01

    INTRODUCTION: The mortality and amputation rates are still high in patients with necrotising soft tissue infections (NSTIs). It would be ideal to have a set of biomarkers that enables the clinician to identify high-risk patients with NSTI on admission. The objectives of this study are to evaluate...... and mortality in patients with NSTI and that HBOT reduces the inflammatory response. METHODS AND ANALYSIS: This is a prospective, observational study being conducted in a tertiary referral centre. Biomarkers will be measured in 114 patients who have been operatively diagnosed with NSTI. On admission, baseline...

  2. De Novo Identification of Biomarker Proteins Using Tandem Mass Spectrometry

    Science.gov (United States)

    Many studies have shown that biological fluids contain an important number of biomarkers associated with various pathologies. For instance, there has been extensive research to identify effective biomarkers as prognostic indicators of breast cancer. An effective approach for biom...

  3. Immune biomarkers in the spectrum of childhood noncommunicable diseases

    NARCIS (Netherlands)

    Skevaki, Chrysanthi; Van Den Berg, Jolice; Jones, Nicholas; Garssen, Johan; Vuillermin, Peter; Levin, Michael; Landay, Alan; Renz, Harald; Calder, Philip C.; Thornton, Catherine A.

    2016-01-01

    A biomarker is an accurately and reproducibly quantifiable biological characteristic that provides an objective measure of health status or disease. Benefits of biomarkers include identification of therapeutic targets, monitoring of clinical interventions, and development of personalized (or

  4. Biomarker Detection using PS2-Thioaptamers, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — AM Biotechnologies (AM) will develop a system to detect and quantify bone demineralization biomarkers as outlined in SBIR Topic "Technologies to Detect Biomarkers"....

  5. Molecular Biomarkers: Their significance and application in marine pollution monitoring

    Digital Repository Service at National Institute of Oceanography (India)

    Sarkar, A.; Ray, D.; Shrivastava, A.N.; Sarkar, S.

    worldwide. Among the various types of biomarkers, the following have received special attention: cytochrome P4501A induction, DNA integrity, acetylcholinesterase activity and metallothionein induction. These biomarkers are being used to evaluate exposure...

  6. Computational genomics of hyperthermophiles

    NARCIS (Netherlands)

    Werken, van de H.J.G.

    2008-01-01

    With the ever increasing number of completely sequenced prokaryotic genomes and the subsequent use of functional genomics tools, e.g. DNA microarray and proteomics, computational data analysis and the integration of microbial and molecular data is inevitable. This thesis describes the computational

  7. Safeguarding genome integrity

    DEFF Research Database (Denmark)

    Sørensen, Claus Storgaard; Syljuåsen, Randi G

    2012-01-01

    Mechanisms that preserve genome integrity are highly important during the normal life cycle of human cells. Loss of genome protective mechanisms can lead to the development of diseases such as cancer. Checkpoint kinases function in the cellular surveillance pathways that help cells to cope with D...

  8. Human genome I

    International Nuclear Information System (INIS)

    Anon.

    1989-01-01

    An international conference, Human Genome I, was held Oct. 2-4, 1989 in San Diego, Calif. Selected speakers discussed: Current Status of the Genome Project; Technique Innovations; Interesting regions; Applications; and Organization - Different Views of Current and Future Science and Procedures. Posters, consisting of 119 presentations, were displayed during the sessions. 119 were indexed for inclusion to the Energy Data Base

  9. Challenging homeostasis to define biomarkers for nutrition related health

    NARCIS (Netherlands)

    Ommen, van B.; Keijer, J.; Heil, S.G.; Kaput, J.

    2009-01-01

    A primary goal of nutrition research is to optimize health and prevent or delay disease. Biomarkers to quantify health optimization are needed since many if not most biomarkers are developed for diseases. Quantifying normal homeostasis and developing validated biomarkers are formidable tasks because

  10. Biomarkers: Delivering on the expectation of molecularly driven, quantitative health.

    Science.gov (United States)

    Wilson, Jennifer L; Altman, Russ B

    2018-02-01

    Biomarkers are the pillars of precision medicine and are delivering on expectations of molecular, quantitative health. These features have made clinical decisions more precise and personalized, but require a high bar for validation. Biomarkers have improved health outcomes in a few areas such as cancer, pharmacogenetics, and safety. Burgeoning big data research infrastructure, the internet of things, and increased patient participation will accelerate discovery in the many areas that have not yet realized the full potential of biomarkers for precision health. Here we review themes of biomarker discovery, current implementations of biomarkers for precision health, and future opportunities and challenges for biomarker discovery. Impact statement Precision medicine evolved because of the understanding that human disease is molecularly driven and is highly variable across patients. This understanding has made biomarkers, a diverse class of biological measurements, more relevant for disease diagnosis, monitoring, and selection of treatment strategy. Biomarkers' impact on precision medicine can be seen in cancer, pharmacogenomics, and safety. The successes in these cases suggest many more applications for biomarkers and a greater impact for precision medicine across the spectrum of human disease. The authors assess the status of biomarker-guided medical practice by analyzing themes for biomarker discovery, reviewing the impact of these markers in the clinic, and highlight future and ongoing challenges for biomarker discovery. This work is timely and relevant, as the molecular, quantitative approach of precision medicine is spreading to many disease indications.

  11. Biomarkører for anorexia nervosa

    DEFF Research Database (Denmark)

    Sjögren, Magnus

    2017-01-01

    Biomarkers for anorexia nervosa (AN) which reflect the pathophysiology and relate to the aetiology of the disease, are warranted and could bring us one step closer to targeted treatment of AN. Some leads may be found in the biochemistry which often is found disturbed in AN, although normalization...

  12. Plasma inflammatory biomarkers response to aerobic versus ...

    African Journals Online (AJOL)

    Plasma inflammatory biomarkers response to aerobic versus resisted exercise training for chronic obstructive pulmonary disease patients. ... Recent studies proved that morbidity and mortality of COPD is related to systemic inflammation as it contributes to the pathogenesis of atherosclerosis and cardiovascular disease.

  13. Stratum corneum biomarkers for inflammatory skin diseases

    NARCIS (Netherlands)

    Koppes, S.A.

    2017-01-01

    This thesis focusses on development of biomarkers, obtained by a non-invasive sampling method, for skin inflammatory diseases relevant for occupational settings; irritant contact dermatitis (ICD), allergic contact dermatitis (ACD) and atopic dermatitis (AD). In various studies, in which different

  14. Cerebrospinal fluid biomarkers for Parkinson's disease

    DEFF Research Database (Denmark)

    Dammann Andersen, Andreas; Binzer, Michael; Stenager, Egon

    2017-01-01

    Diagnosticering af Parkinson's sygdom (PD) er baseret på den kliniske udvikling af sygdommen samt en fysisk undersøgelse af patienten, men fejldiagnosticering sker hyppigt; specielt i tidlige stadier. Biomarkører for PD kan muliggøre en tidligere og mere præcis diagnosticering samt monitorering a...

  15. Biomarkers of problem drinking in homeless patients

    DEFF Research Database (Denmark)

    Hesse, Morten; Thiesen, Henrik

    2010-01-01

    Objective. In the search for optimal biomarkers of excessive drinking, a central limitation has been the lack of sensitivity of measures. Many patients have apparently normal values of liver markers despite a considerable alcohol intake. This study aimed to test a novel combined indicator...

  16. Biomarkers in pancreatic adenocarcinoma: current perspectives

    Directory of Open Access Journals (Sweden)

    Swords DS

    2016-12-01

    Full Text Available Douglas S Swords, Matthew A Firpo, Courtney L Scaife, Sean J Mulvihill Department of Surgery, University of Utah Health Sciences, Salt Lake City, UT, USA Abstract: Pancreatic ductal adenocarcinoma (PDAC has a poor prognosis, with a 5-year survival rate of 7.7%. Most patients are diagnosed at an advanced stage not amenable to potentially curative resection. A substantial portion of this review is dedicated to reviewing the current literature on carbohydrate antigen (CA 19-9, which is currently the only guideline-recommended biomarker for PDAC. It provides valuable prognostic information, can predict resectability, and is useful in decision making about neoadjuvant therapy. We also discuss carcinoembryonic antigen (CEA, CA 125, serum biomarker panels, circulating tumor cells, and cell-free nucleic acids. Although many biomarkers have now been studied in relation to PDAC, significant work still needs to be done to validate their usefulness in the early detection of PDAC and management of patients with PDAC. Keywords: pancreatic cancer, biomarkers, screening, CA 19-9, CEA

  17. Quantitative multiplex detection of pathogen biomarkers

    Energy Technology Data Exchange (ETDEWEB)

    Mukundan, Harshini; Xie, Hongzhi; Swanson, Basil I.; Martinez, Jennifer; Grace, Wynne K.

    2016-02-09

    The present invention addresses the simultaneous detection and quantitative measurement of multiple biomolecules, e.g., pathogen biomarkers through either a sandwich assay approach or a lipid insertion approach. The invention can further employ a multichannel, structure with multi-sensor elements per channel.

  18. Quantitative multiplex detection of pathogen biomarkers

    Science.gov (United States)

    Mukundan, Harshini; Xie, Hongzhi; Swanson, Basil I; Martinez, Jennifer; Grace, Wynne K

    2014-10-14

    The present invention addresses the simultaneous detection and quantitative measurement of multiple biomolecules, e.g., pathogen biomarkers through either a sandwich assay approach or a lipid insertion approach. The invention can further employ a multichannel, structure with multi-sensor elements per channel.

  19. BLOOD BIOMARKERS FOR EVALUATION OF PERINATAL ENCEPHALOPATHY

    Directory of Open Access Journals (Sweden)

    Ernest Marshall Graham

    2016-07-01

    Full Text Available Recent research in identification of brain injury after trauma shows many possible blood biomarkers that may help identify the fetus and neonate with encephalopathy. Traumatic brain injury shares many common features with perinatal hypoxic-ischemic encephalopathy. Trauma has a hypoxic component, and one of the 1st physiologic consequences of moderate-severe traumatic brain injury is apnea. Trauma and hypoxia-ischemia initiate an excitotoxic cascade and free radical injury followed by the inflammatory cascade, producing injury in neurons, glial cells and white matter. Increased excitatory amino acids, lipid peroxidation products and alteration in microRNAs and inflammatory markers are common to both traumatic brain injury and perinatal encephalopathy. The blood-brain barrier is disrupted in both leading to egress of substances normally only found in the central nervous system. Brain exosomes may represent ideal biomarker containers, as RNA and protein transported within the vesicles are protected from enzymatic degradation. Evaluation of fetal or neonatal brain derived exosomes that cross the blood-brain barrier and circulate peripherally has been referred to as the liquid brain biopsy. A multiplex of serum biomarkers could improve upon the current imprecise methods of identifying fetal and neonatal brain injury such as fetal heart rate abnormalities, meconium, cord gases at delivery, and Apgar scores. Quantitative biomarker measurements of perinatal brain injury and recovery could lead to operative delivery only in the presence of significant fetal risk, triage to appropriate therapy after birth and measure the effectiveness of treatment.

  20. Biomarker Guided Therapy in Chronic Heart Failure

    Science.gov (United States)

    Bektas, Sema

    2015-01-01

    This review article addresses the question of whether biomarker-guided therapy is ready for clinical implementation in chronic heart failure. The most well-known biomarkers in heart failure are natriuretic peptides, namely B-type natriuretic peptide (BNP) and N-terminal pro-BNP. They are well-established in the diagnostic process of acute heart failure and prediction of disease prognosis. They may also be helpful in screening patients at risk of developing heart failure. Although studied by 11 small- to medium-scale trials resulting in several positive meta-analyses, it is less well-established whether natriuretic peptides are also helpful for guiding chronic heart failure therapy. This uncertainty is expressed by differences in European and American guideline recommendations. In addition to reviewing the evidence surrounding the use of natriuretic peptides to guide chronic heart failure therapy, this article gives an overview of the shortcomings of the trials, how the results may be interpreted and the future directions necessary to fill the current gaps in knowledge. Therapy guidance in chronic heart failure using other biomarkers has not been prospectively tested to date. Emerging biomarkers, such as galectin-3 and soluble ST2, might be useful in this regard, as suggested by several post-hoc analyses. PMID:28785440

  1. Biomarkers of Hypoxic Ischemic Encephalopathy in Newborns

    Directory of Open Access Journals (Sweden)

    Martha V. Douglas-Escobar

    2012-11-01

    Full Text Available As neonatal intensive care has evolved, the focus has shifted from improving mortality alone to an effort to improve both mortality and morbidity. The most frequent source of neonatal brain injury occurs as a result of hypoxic-ischemic injury. Hypoxic-ischemic injury occurs in about 2 of 1,000 full-term infants and severe injured infants will have lifetime disabilities and neurodevelopmental delays. Most recently, remarkable efforts toward neuroprotection have been started with the advent of therapeutic hypothermia and a key step in the evolution of neonatal neuroprotection is the discovery of biomarkers that enable the clinician-scientist to screen infants for brain injury, monitor progression of disease, identify injured brain regions, and assess efficacy of neuroprotective clinical trials. Lastly, biomarkers offer great hope identifying when an injury occurred shedding light on the potential pathophysiology and the most effective therapy. In this article, we will review biomarkers of HIE including S100b, neuron specific enolase, umbilical cord IL-6, CK-BB, GFAP, myelin basic protein, UCHL-1, and pNF-H. We hope to contribute to the awareness, validation and clinical use of established as well as novel neonatal brain injury biomarkers.

  2. Imaging biomarkers in primary brain tumours

    Energy Technology Data Exchange (ETDEWEB)

    Lopci, Egesta; Chiti, Arturo [Humanitas Clinical and Research Center, Nuclear Medicine Department, Rozzano, MI (Italy); Franzese, Ciro; Navarria, Pierina; Scorsetti, Marta [Humanitas Clinical and Research Center, Radiosurgery and Radiotherapy, Rozzano, MI (Italy); Grimaldi, Marco [Humanitas Clinical and Research Center, Radiology, Rozzano, MI (Italy); Zucali, Paolo Andrea; Simonelli, Matteo [Humanitas Clinical and Research Center, Medical Oncology, Rozzano, MI (Italy); Bello, Lorenzo [Humanitas Clinical and Research Center, Neurosurgery, Rozzano, MI (Italy)

    2015-04-01

    We are getting used to referring to instrumentally detectable biological features in medical language as ''imaging biomarkers''. These two terms combined reflect the evolution of medical imaging during recent decades, and conceptually comprise the principle of noninvasive detection of internal processes that can become targets for supplementary therapeutic strategies. These targets in oncology include those biological pathways that are associated with several tumour features including independence from growth and growth-inhibitory signals, avoidance of apoptosis and immune system control, unlimited potential for replication, self-sufficiency in vascular supply and neoangiogenesis, acquired tissue invasiveness and metastatic diffusion. Concerning brain tumours, there have been major improvements in neurosurgical techniques and radiotherapy planning, and developments of novel target drugs, thus increasing the need for reproducible, noninvasive, quantitative imaging biomarkers. However, in this context, conventional radiological criteria may be inappropriate to determine the best therapeutic option and subsequently to assess response to therapy. Integration of molecular imaging for the evaluation of brain tumours has for this reason become necessary, and an important role in this setting is played by imaging biomarkers in PET and MRI. In the current review, we describe most relevant techniques and biomarkers used for imaging primary brain tumours in clinical practice, and discuss potential future developments from the experimental context. (orig.)

  3. Biomarkers and Genetics in Peripheral Artery Disease.

    Science.gov (United States)

    Hazarika, Surovi; Annex, Brian H

    2017-01-01

    Peripheral artery disease (PAD) is highly prevalent and there is considerable diversity in the initial clinical manifestation and disease progression among individuals. Currently, there is no ideal biomarker to screen for PAD, to risk stratify patients with PAD, or to monitor therapeutic response to revascularization procedures. Advances in human genetics have markedly enhanced the ability to develop novel diagnostic and therapeutic approaches across a host of human diseases, but such developments in the field of PAD are lagging. In this article, we will discuss the epidemiology, traditional risk factors for, and clinical presentations of PAD. We will discuss the possible role of genetic factors and gene-environment interactions in the development and/or progression of PAD. We will further explore future avenues through which genetic advances can be used to better our understanding of the pathophysiology of PAD and potentially find newer therapeutic targets. We will discuss the potential role of biomarkers in identifying patients at risk for PAD and for risk stratifying patients with PAD, and novel approaches to identification of reliable biomarkers in PAD. The exponential growth of genetic tools and newer technologies provides opportunities to investigate and identify newer pathways in the development and progression of PAD, and thereby in the identification of newer biomarkers and therapies. © 2016 American Association for Clinical Chemistry.

  4. Phospholipids as Biomarkers for Excessive Alcohol Use

    Science.gov (United States)

    2013-10-01

    NUMBER Phospholipids as Biomarkers for Excessive Alcohol Use 5b. GRANT NUMBER W81XWH-12-1-0497 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...suspected of alcohol abuse. Toxicol Lett, 151(1), 235-241. Graham, D. P., Cardon , A. L., & Uhl, G. R. (2008). An update on substance use and treatment

  5. Blood Biomarkers in Idiopathic Pulmonary Fibrosis.

    Science.gov (United States)

    Guiot, Julien; Moermans, Catherine; Henket, Monique; Corhay, Jean-Louis; Louis, Renaud

    2017-06-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease of unknown origin whose incidence has been increasing over the latest decade partly as a consequence of population ageing. New anti-fibrotic therapy including pirfenidone and nintedanib have now proven efficacy in slowing down the disease. Nevertheless, diagnosis and follow-up of IPF remain challenging. This review examines the recent literature on potentially useful blood molecular and cellular biomarkers in IPF. Most of the proposed biomarkers belong to chemokines (IL-8, CCL18), proteases (MMP-1 and MMP-7), and growth factors (IGBPs) families. Circulating T cells and fibrocytes have also gained recent interest in that respect. Up to now, though several interesting candidates are profiling there has not been a single biomarker, which proved to be specific of the disease and predictive of the evolution (decline of pulmonary function test values, risk of acute exacerbation or mortality). Large scale multicentric studies are eagerly needed to confirm the utility of these biomarkers.

  6. Plasma biomarker of dietary phytosterol intake.

    Directory of Open Access Journals (Sweden)

    Xiaobo Lin

    Full Text Available Dietary phytosterols, plant sterols structurally similar to cholesterol, reduce intestinal cholesterol absorption and have many other potentially beneficial biological effects in humans. Due to limited information on phytosterol levels in foods, however, it is difficult to quantify habitual dietary phytosterol intake (DPI. Therefore, we sought to identify a plasma biomarker of DPI.Data were analyzed from two feeding studies with a total of 38 subjects during 94 dietary periods. DPI was carefully controlled at low, intermediate, and high levels. Plasma levels of phytosterols and cholesterol metabolites were assessed at the end of each diet period. Based on simple ordinary least squares regression analysis, the best biomarker for DPI was the ratio of plasma campesterol to the endogenous cholesterol metabolite 5-α-cholestanol (R2 = 0.785, P 0.600; P < 0.01.The ratio of plasma campesterol to the coordinately regulated endogenous cholesterol metabolite 5-α-cholestanol is a biomarker of dietary phytosterol intake. Conversely, plasma phytosterol levels alone are not ideal biomarkers of DPI because they are confounded by large inter-individual variation in absorption and turnover of non-cholesterol sterols. Further work is needed to assess the relation between non-cholesterol sterol metabolism and associated cholesterol transport in the genesis of coronary heart disease.

  7. Functional MRI and CT biomarkers in oncology

    Energy Technology Data Exchange (ETDEWEB)

    Winfield, J.M. [Institute of Cancer Research and Royal Marsden NHS Foundation Trust, CRUK Imaging Centre at the Institute of Cancer Research, Sutton (United Kingdom); Institute of Cancer Research and Royal Marsden Hospital, MRI Unit, Sutton (United Kingdom); Payne, G.S.; DeSouza, N.M. [Institute of Cancer Research and Royal Marsden NHS Foundation Trust, CRUK Imaging Centre at the Institute of Cancer Research, Sutton (United Kingdom)

    2015-04-01

    Imaging biomarkers derived from MRI or CT describe functional properties of tumours and normal tissues. They are finding increasing numbers of applications in diagnosis, monitoring of response to treatment and assessment of progression or recurrence. Imaging biomarkers also provide scope for assessment of heterogeneity within and between lesions. A wide variety of functional parameters have been investigated for use as biomarkers in oncology. Some imaging techniques are used routinely in clinical applications while others are currently restricted to clinical trials or preclinical studies. Apparent diffusion coefficient, magnetization transfer ratio and native T{sub 1} relaxation time provide information about structure and organization of tissues. Vascular properties may be described using parameters derived from dynamic contrast-enhanced MRI, dynamic contrast-enhanced CT, transverse relaxation rate (R{sub 2}*), vessel size index and relative blood volume, while magnetic resonance spectroscopy may be used to probe the metabolic profile of tumours. This review describes the mechanisms of contrast underpinning each technique and the technical requirements for robust and reproducible imaging. The current status of each biomarker is described in terms of its validation, qualification and clinical applications, followed by a discussion of the current limitations and future perspectives. (orig.)

  8. Cellular biomarker responses of bagrid catfish, Chrysichthys ...

    African Journals Online (AJOL)

    An assessment of the pollution status of Agboyi creek, a water body associated with various anthropogenic activities was carried out in order to determine responses induced in Catfishes, Chrysichthys nigrodigitatus inhabiting it. Cellular biomarkers of stress including the antioxidative stress enzyme, catalase (CAT), lipid ...

  9. Biomarkers of drug-induced vascular injury

    International Nuclear Information System (INIS)

    Brott, D.; Gould, S.; Jones, H.; Schofield, J.; Prior, H.; Valentin, J.P; Bjurstrom, S.; Kenne, K.; Schuppe-Koistinen, I.; Katein, A.; Foster-Brown, L.; Betton, G.; Richardson, R.; Evans, G.; Louden, C.

    2005-01-01

    In pre-clinical safety studies, drug-induced vascular injury is an issue of concern because there are no obvious diagnostic markers for pre-clinical or clinical monitoring and there is an intellectual gap in our understanding of the pathogenesis of this lesion. While vasodilatation and increased shear stress appear to play a role, the exact mechanism(s) of injury to the primary targets, smooth muscle and endothelial cells are unknown. However, evaluation of novel markers for potential clinical monitoring with a mechanistic underpinning would add value in risk assessment and management. This mini review focuses on the progress to identify diagnostic markers of drug-induced vascular injury. Von Willebrand factor (vWF), released upon perturbation of endothelial cells, is transiently increased in plasma prior to morphological evidence of damage in dogs or rats treated with vascular toxicants. Therefore, vWF might be a predictive biomarker of vascular injury. However, vWF is not an appropriate biomarker of lesion progression or severity since levels return to baseline values when there is morphological evidence of injury. A potential mechanistically linked biomarker of vascular injury is caveolin-1. Expression of this protein, localized primarily to smooth muscle and endothelial cells, decreases with the onset of vascular damage. Since vascular injury involves multiple mediators and cell types, evaluation of a panel rather than a single biomarker may be more useful in monitoring early and severe progressive vascular injury

  10. Pulmonary biomarkers in chronic obstructive pulmonary disease

    NARCIS (Netherlands)

    Barnes, Peter J.; Chowdhury, Badrul; Kharitonov, Sergei A.; Magnussen, Helgo; Page, Clive P.; Postma, Dirkje; Saetta, Marina

    2006-01-01

    There has been increasing interest in using pulmonary biomarkers to understand and monitor the inflammation in the respiratory tract of patients with chronic obstructive pulmonary disease (COPD). In this Pulmonary Perspective we discuss the merits of the various approaches by reviewing the current

  11. Biomarkers and Prognosis in Malignant Lymphomas

    NARCIS (Netherlands)

    Hagenbeek, Anton; Gascoyne, Randy D.; Dreyling, Martin; Kluin, Philip; Engert, Andreas; Salles, Gilles

    2009-01-01

    Approximately 100 hematologists and pathologists from Europe, the United States, and Canada participated in the workshop Biomarkers and Prognosis in Malignant Lymphomas, held in Mandelieu, France,April 11-13, 2008, under the leadership of Anton Hagenbeek, Randy Gascoyne, and Gilles Salles.

  12. Blood-borne biomarkers and bioindicators for linking exposure to health effects in environmental health science.

    Science.gov (United States)

    Wallace, M Ariel Geer; Kormos, Tzipporah M; Pleil, Joachim D

    2016-01-01

    Environmental health science aims to link environmental pollution sources to adverse health outcomes to develop effective exposure intervention strategies that reduce long-term disease risks. Over the past few decades, the public health community recognized that health risk is driven by interaction between the human genome and external environment. Now that the human genetic code has been sequenced, establishing this "G × E" (gene-environment) interaction requires a similar effort to decode the human exposome, which is the accumulation of an individual's environmental exposures and metabolic responses throughout the person's lifetime. The exposome is composed of endogenous and exogenous chemicals, many of which are measurable as biomarkers in blood, breath, and urine. Exposure to pollutants is assessed by analyzing biofluids for the pollutant itself or its metabolic products. New methods are being developed to use a subset of biomarkers, termed bioindicators, to demonstrate biological changes indicative of future adverse health effects. Typically, environmental biomarkers are assessed using noninvasive (excreted) media, such as breath and urine. Blood is often avoided for biomonitoring due to practical reasons such as medical personnel, infectious waste, or clinical setting, despite the fact that blood represents the central compartment that interacts with every living cell and is the most relevant biofluid for certain applications and analyses. The aims of this study were to (1) review the current use of blood samples in environmental health research, (2) briefly contrast blood with other biological media, and (3) propose additional applications for blood analysis in human exposure research.

  13. Metabolomics approaches for discovering biomarkers of drug-induced hepatotoxicity and nephrotoxicity

    International Nuclear Information System (INIS)

    Beger, Richard D.; Sun, Jinchun; Schnackenberg, Laura K.

    2010-01-01

    Hepatotoxicity and nephrotoxicity are two major reasons that drugs are withdrawn post-market, and hence it is of major concern to both the FDA and pharmaceutical companies. The number of cases of serious adverse effects (SAEs) in marketed drugs has climbed faster than the number of total drug prescriptions issued. In some cases, preclinical animal studies fail to identify the potential toxicity of a new chemical entity (NCE) under development. The current clinical chemistry biomarkers of liver and kidney injury are inadequate in terms of sensitivity and/or specificity, prompting the need to discover new translational specific biomarkers of organ injury. Metabolomics along with genomics and proteomics technologies have the capability of providing translational diagnostic and prognostic biomarkers specific for early stages of liver and kidney injury. Metabolomics has several advantages over the other omics platforms such as ease of sample preparation, data acquisition and use of biofluids collected through minimally invasive procedures in preclinical and clinical studies. The metabolomics platform is reviewed with particular emphasis on applications involving drug-induced hepatotoxicity and nephrotoxicity. Analytical platforms for metabolomics, chemometrics for mining metabolomics data and the applications of the metabolomics technologies are covered in detail with emphasis on recent work in the field.

  14. Precision Oncology Medicine: The Clinical Relevance of Patient-Specific Biomarkers Used to Optimize Cancer Treatment.

    Science.gov (United States)

    Schmidt, Keith T; Chau, Cindy H; Price, Douglas K; Figg, William D

    2016-12-01

    Precision medicine in oncology is the result of an increasing awareness of patient-specific clinical features coupled with the development of genomic-based diagnostics and targeted therapeutics. Companion diagnostics designed for specific drug-target pairs were the first to widely utilize clinically applicable tumor biomarkers (eg, HER2, EGFR), directing treatment for patients whose tumors exhibit a mutation susceptible to an FDA-approved targeted therapy (eg, trastuzumab, erlotinib). Clinically relevant germline mutations in drug-metabolizing enzymes and transporters (eg, TPMT, DPYD) have been shown to impact drug response, providing a rationale for individualized dosing to optimize treatment. The use of multigene expression-based assays to analyze an array of prognostic biomarkers has been shown to help direct treatment decisions, especially in breast cancer (eg, Oncotype DX). More recently, the use of next-generation sequencing to detect many potential "actionable" cancer molecular alterations is further shifting the 1 gene-1 drug paradigm toward a more comprehensive, multigene approach. Currently, many clinical trials (eg, NCI-MATCH, NCI-MPACT) are assessing novel diagnostic tools with a combination of different targeted therapeutics while also examining tumor biomarkers that were previously unexplored in a variety of cancer histologies. Results from ongoing trials such as the NCI-MATCH will help determine the clinical utility and future development of the precision-medicine approach. © 2016, The American College of Clinical Pharmacology.

  15. How Nanotechnology and Biomedical Engineering Are Supporting the Identification of Predictive Biomarkers in Neuro-Oncology.

    Science.gov (United States)

    Ganau, Mario; Paris, Marco; Syrmos, Nikolaos; Ganau, Laura; Ligarotti, Gianfranco K I; Moghaddamjou, Ali; Prisco, Lara; Ambu, Rossano; Chibbaro, Salvatore

    2018-02-26

    The field of neuro-oncology is rapidly progressing and internalizing many of the recent discoveries coming from research conducted in basic science laboratories worldwide. This systematic review aims to summarize the impact of nanotechnology and biomedical engineering in defining clinically meaningful predictive biomarkers with a potential application in the management of patients with brain tumors. Data were collected through a review of the existing English literature performed on Scopus, MEDLINE, MEDLINE in Process, EMBASE, and/or Cochrane Central Register of Controlled Trials: all available basic science and clinical papers relevant to address the above-stated research question were included and analyzed in this study. Based on the results of this systematic review we can conclude that: (1) the advances in nanotechnology and bioengineering are supporting tremendous efforts in optimizing the methods for genomic, epigenomic and proteomic profiling; (2) a successful translational approach is attempting to identify a growing number of biomarkers, some of which appear to be promising candidates in many areas of neuro-oncology; (3) the designing of Randomized Controlled Trials will be warranted to better define the prognostic value of those biomarkers and biosignatures.

  16. How Nanotechnology and Biomedical Engineering Are Supporting the Identification of Predictive Biomarkers in Neuro-Oncology

    Directory of Open Access Journals (Sweden)

    Mario Ganau

    2018-02-01

    Full Text Available The field of neuro-oncology is rapidly progressing and internalizing many of the recent discoveries coming from research conducted in basic science laboratories worldwide. This systematic review aims to summarize the impact of nanotechnology and biomedical engineering in defining clinically meaningful predictive biomarkers with a potential application in the management of patients with brain tumors. Data were collected through a review of the existing English literature performed on Scopus, MEDLINE, MEDLINE in Process, EMBASE, and/or Cochrane Central Register of Controlled Trials: all available basic science and clinical papers relevant to address the above-stated research question were included and analyzed in this study. Based on the results of this systematic review we can conclude that: (1 the advances in nanotechnology and bioengineering are supporting tremendous efforts in optimizing the methods for genomic, epigenomic and proteomic profiling; (2 a successful translational approach is attempting to identify a growing number of biomarkers, some of which appear to be promising candidates in many areas of neuro-oncology; (3 the designing of Randomized Controlled Trials will be warranted to better define the prognostic value of those biomarkers and biosignatures.

  17. Innovative biomarkers in psychiatric disorders: a major clinical challenge in psychiatry.

    Science.gov (United States)

    Lozupone, Madia; Seripa, Davide; Stella, Eleonora; La Montagna, Maddalena; Solfrizzi, Vincenzo; Quaranta, Nicola; Veneziani, Federica; Cester, Alberto; Sardone, Rodolfo; Bonfiglio, Caterina; Giannelli, Gianluigi; Bisceglia, Paola; Bringiotti, Roberto; Daniele, Antonio; Greco, Antonio; Bellomo, Antonello; Logroscino, Giancarlo; Panza, Francesco

    2017-09-01

    Currently, the diagnosis of psychiatric illnesses is based upon DSM-5 criteria. Although endophenotype-specificity for a particular disorder is discussed, the identification of objective biomarkers is ongoing for aiding diagnosis, prognosis, or clinical response to treatment. We need to improve the understanding of the biological abnormalities in psychiatric illnesses across conventional diagnostic boundaries. The present review investigates the innovative post-genomic knowledge used for psychiatric illness diagnostics and treatment response, with a particular focus on proteomics. Areas covered: This review underlines the contribution that psychiatric innovative biomarkers have reached in relation to diagnosis and theragnosis of psychiatric illnesses. Furthermore, it encompasses a reliable representation of their involvement in disease through proteomics, metabolomics/pharmacometabolomics and lipidomics techniques, including the possible role that gut microbiota and CYP2D6 polimorphisms may play in psychiatric illnesses. Expert opinion: Etiologic heterogeneity, variable expressivity, and epigenetics may impact clinical manifestations, making it difficult for a single measurement to be pathognomonic for multifaceted psychiatric disorders. Academic, industry, or government's partnerships may successfully identify and validate new biomarkers so that unfailing clinical tests can be developed. Proteomics, metabolomics, and lipidomics techniques are considered to be helpful tools beyond neuroimaging and neuropsychology for the phenotypic characterization of brain diseases.

  18. Genetic biomarkers for brain hemisphere differentiation in Parkinson's Disease

    Science.gov (United States)

    Hourani, Mou'ath; Mendes, Alexandre; Berretta, Regina; Moscato, Pablo

    2007-11-01

    This work presents a study on the genetic profile of the left and right hemispheres of the brain of a mouse model of Parkinson's disease (PD). The goal is to characterize, in a genetic basis, PD as a disease that affects these two brain regions in different ways. Using the same whole-genome microarray expression data introduced by Brown et al. (2002) [1], we could find significant differences in the expression of some key genes, well-known to be involved in the mechanisms of dopamine production control and PD. The problem of selecting such genes was modeled as the MIN (α,β)—FEATURE SET problem [2]; a similar approach to that employed previously to find biomarkers for different types of cancer using gene expression microarray data [3]. The Feature Selection method produced a series of genetic signatures for PD, with distinct expression profiles in the Parkinson's model and control mice experiments. In addition, a close examination of the genes composing those signatures shows that many of them belong to genetic pathways or have ontology annotations considered to be involved in the onset and development of PD. Such elements could provide new clues on which mechanisms are implicated in hemisphere differentiation in PD.

  19. Chronic psychosocial stressors and salivary biomarkers in emerging adults.

    Science.gov (United States)

    Bergen, Andrew W; Mallick, Aditi; Nishita, Denise; Wei, Xin; Michel, Martha; Wacholder, Aaron; David, Sean P; Swan, Gary E; Reid, Mark W; Simons, Anne; Andrews, Judy A

    2012-08-01

    We investigated whole saliva as a source of biomarkers to distinguish individuals who have, and who have not, been chronically exposed to severe and threatening life difficulties. We evaluated RNA and DNA metrics, expression of 37 candidate genes, and cortisol release in response to the Trier Social Stress Test, as well as clinical characteristics, from 48 individuals stratified on chronic exposure to psychosocial stressors within the last year as measured by the Life Events and Difficulties Schedule. Candidate genes were selected based on their differential gene expression ratio in circulating monocytes from a published genome-wide analysis of adults experiencing different levels of exposure to a chronic stressor. In univariate analyses, we observed significantly decreased RNA integrity (RIN) score (P = 0.04), and reduced expression of glucocorticoid receptor-regulated genes (Ps stressors, as compared to those with no exposure. In those exposed, we observed significantly decreased BMI (P adults chronically exposed to severe and threatening psychosocial stressors. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Rumen microbial genomics

    International Nuclear Information System (INIS)

    Morrison, M.; Nelson, K.E.

    2005-01-01

    Improving microbial degradation of plant cell wall polysaccharides remains one of the highest priority goals for all livestock enterprises, including the cattle herds and draught animals of developing countries. The North American Consortium for Genomics of Fibrolytic Ruminal Bacteria was created to promote the sequencing and comparative analysis of rumen microbial genomes, offering the potential to fully assess the genetic potential in a functional and comparative fashion. It has been found that the Fibrobacter succinogenes genome encodes many more endoglucanases and cellodextrinases than previously isolated, and several new processive endoglucanases have been identified by genome and proteomic analysis of Ruminococcus albus, in addition to a variety of strategies for its adhesion to fibre. The ramifications of acquiring genome sequence data for rumen microorganisms are profound, including the potential to elucidate and overcome the biochemical, ecological or physiological processes that are rate limiting for ruminal fibre degradation. (author)

  1. Microbial Genomes Multiply

    Science.gov (United States)

    Doolittle, Russell F.

    2002-01-01

    The publication of the first complete sequence of a bacterial genome in 1995 was a signal event, underscored by the fact that the article has been cited more than 2,100 times during the intervening seven years. It was a marvelous technical achievement, made possible by automatic DNA-sequencing machines. The feat is the more impressive in that complete genome sequencing has now been adopted in many different laboratories around the world. Four years ago in these columns I examined the situation after a dozen microbial genomes had been completed. Now, with upwards of 60 microbial genome sequences determined and twice that many in progress, it seems reasonable to assess just what is being learned. Are new concepts emerging about how cells work? Have there been practical benefits in the fields of medicine and agriculture? Is it feasible to determine the genomic sequence of every bacterial species on Earth? The answers to these questions maybe Yes, Perhaps, and No, respectively.

  2. Musa sebagai Model Genom

    Directory of Open Access Journals (Sweden)

    RITA MEGIA

    2005-12-01

    Full Text Available During the meeting in Arlington, USA in 2001, the scientists grouped in PROMUSA agreed with the launching of the Global Musa Genomics Consortium. The Consortium aims to apply genomics technologies to the improvement of this important crop. These genome projects put banana as the third model species after Arabidopsis and rice that will be analyzed and sequenced. Comparing to Arabidopsis and rice, banana genome provides a unique and powerful insight into structural and in functional genomics that could not be found in those two species. This paper discussed these subjects-including the importance of banana as the fourth main food in the world, the evolution and biodiversity of this genetic resource and its parasite.

  3. The genome editing revolution

    DEFF Research Database (Denmark)

    Stella, Stefano; Montoya, Guillermo

    2016-01-01

    -Cas system has become the main tool for genome editing in many laboratories. Currently the targeted genome editing technology has been used in many fields and may be a possible approach for human gene therapy. Furthermore, it can also be used to modifying the genomes of model organisms for studying human......In the last 10 years, we have witnessed a blooming of targeted genome editing systems and applications. The area was revolutionized by the discovery and characterization of the transcription activator-like effector proteins, which are easier to engineer to target new DNA sequences than...... sequence). This ribonucleoprotein complex protects bacteria from invading DNAs, and it was adapted to be used in genome editing. The CRISPR ribonucleic acid (RNA) molecule guides to the specific DNA site the Cas9 nuclease to cleave the DNA target. Two years and more than 1000 publications later, the CRISPR...

  4. Genomic Heterogeneity as a Barrier to Precision Medicine in Gastroesophageal Adenocarcinoma.

    Science.gov (United States)

    Pectasides, Eirini; Stachler, Matthew D; Derks, Sarah; Liu, Yang; Maron, Steven; Islam, Mirazul; Alpert, Lindsay; Kwak, Heewon; Kindler, Hedy; Polite, Blase; Sharma, Manish R; Allen, Kenisha; O'Day, Emily; Lomnicki, Samantha; Maranto, Melissa; Kanteti, Rajani; Fitzpatrick, Carrie; Weber, Christopher; Setia, Namrata; Xiao, Shu-Yuan; Hart, John; Nagy, Rebecca J; Kim, Kyoung-Mee; Choi, Min-Gew; Min, Byung-Hoon; Nason, Katie S; O'Keefe, Lea; Watanabe, Masayuki; Baba, Hideo; Lanman, Rick; Agoston, Agoston T; Oh, David J; Dunford, Andrew; Thorner, Aaron R; Ducar, Matthew D; Wollison, Bruce M; Coleman, Haley A; Ji, Yuan; Posner, Mitchell C; Roggin, Kevin; Turaga, Kiran; Chang, Paul; Hogarth, Kyle; Siddiqui, Uzma; Gelrud, Andres; Ha, Gavin; Freeman, Samuel S; Rhoades, Justin; Reed, Sarah; Gydush, Greg; Rotem, Denisse; Davison, Jon; Imamura, Yu; Adalsteinsson, Viktor; Lee, Jeeyun; Bass, Adam J; Catenacci, Daniel V

    2018-01-01

    Gastroesophageal adenocarcinoma (GEA) is a lethal disease where targeted therapies, even when guided by genomic biomarkers, have had limited efficacy. A potential reason for the failure of such therapies is that genomic profiling results could commonly differ between the primary and metastatic tumors. To evaluate genomic heterogeneity, we sequenced paired primary GEA and synchronous metastatic lesions across multiple cohorts, finding extensive differences in genomic alterations, including discrepancies in potentially clinically relevant alterations. Multiregion sequencing showed significant discrepancy within the primary tumor (PT) and between the PT and disseminated disease, with oncogene amplification profiles commonly discordant. In addition, a pilot analysis of cell-free DNA (cfDNA) sequencing demonstrated the feasibility of detecting genomic amplifications not detected in PT sampling. Lastly, we profiled paired primary tumors, metastatic tumors, and cfDNA from patients enrolled in the personalized antibodies for GEA (PANGEA) trial of targeted therapies in GEA and found that genomic biomarkers were recurrently discrepant between the PT and untreated metastases. Divergent primary and metastatic tissue profiling led to treatment reassignment in 32% (9/28) of patients. In discordant primary and metastatic lesions, we found 87.5% concordance for targetable alterations in metastatic tissue and cfDNA, suggesting the potential for cfDNA profiling to enhance selection of therapy. Significance: We demonstrate frequent baseline heterogeneity in targetable genomic alterations in GEA, indicating that current tissue sampling practices for biomarker testing do not effectively guide precision medicine in this disease and that routine profiling of metastatic lesions and/or cfDNA should be systematically evaluated. Cancer Discov; 8(1); 37-48. ©2017 AACR. See related commentary by Sundar and Tan, p. 14 See related article by Janjigian et al., p. 49 This article is highlighted

  5. A sequence-based survey of the complex structural organization of tumor genomes

    Energy Technology Data Exchange (ETDEWEB)

    Collins, Colin; Raphael, Benjamin J.; Volik, Stanislav; Yu, Peng; Wu, Chunxiao; Huang, Guiqing; Linardopoulou, Elena V.; Trask, Barbara J.; Waldman, Frederic; Costello, Joseph; Pienta, Kenneth J.; Mills, Gordon B.; Bajsarowicz, Krystyna; Kobayashi, Yasuko; Sridharan, Shivaranjani; Paris, Pamela; Tao, Quanzhou; Aerni, Sarah J.; Brown, Raymond P.; Bashir, Ali; Gray, Joe W.; Cheng, Jan-Fang; de Jong, Pieter; Nefedov, Mikhail; Ried, Thomas; Padilla-Nash, Hesed M.; Collins, Colin C.

    2008-04-03

    The genomes of many epithelial tumors exhibit extensive chromosomal rearrangements. All classes of genome rearrangements can be identified using End Sequencing Profiling (ESP), which relies on paired-end sequencing of cloned tumor genomes. In this study, brain, breast, ovary and prostate tumors along with three breast cancer cell lines were surveyed with ESP yielding the largest available collection of sequence-ready tumor genome breakpoints and providing evidence that some rearrangements may be recurrent. Sequencing and fluorescence in situ hybridization (FISH) confirmed translocations and complex tumor genome structures that include coamplification and packaging of disparate genomic loci with associated molecular heterogeneity. Comparison of the tumor genomes suggests recurrent rearrangements. Some are likely to be novel structural polymorphisms, whereas others may be bona fide somatic rearrangements. A recurrent fusion transcript in breast tumors and a constitutional fusion transcript resulting from a segmental duplication were identified. Analysis of end sequences for single nucleotide polymorphisms (SNPs) revealed candidate somatic mutations and an elevated rate of novel SNPs in an ovarian tumor. These results suggest that the genomes of many epithelial tumors may be far more dynamic and complex than previously appreciated and that genomic fusions including fusion transcripts and proteins may be common, possibly yielding tumor-specific biomarkers and therapeutic targets.

  6. Phytozome Comparative Plant Genomics Portal

    Energy Technology Data Exchange (ETDEWEB)

    Goodstein, David; Batra, Sajeev; Carlson, Joseph; Hayes, Richard; Phillips, Jeremy; Shu, Shengqiang; Schmutz, Jeremy; Rokhsar, Daniel

    2014-09-09

    The Dept. of Energy Joint Genome Institute is a genomics user facility supporting DOE mission science in the areas of Bioenergy, Carbon Cycling, and Biogeochemistry. The Plant Program at the JGI applies genomic, analytical, computational and informatics platforms and methods to: 1. Understand and accelerate the improvement (domestication) of bioenergy crops 2. Characterize and moderate plant response to climate change 3. Use comparative genomics to identify constrained elements and infer gene function 4. Build high quality genomic resource platforms of JGI Plant Flagship genomes for functional and experimental work 5. Expand functional genomic resources for Plant Flagship genomes

  7. Emerging Biomarkers and Metabolomics for Assessing Toxic Nephropathy and Acute Kidney Injury (AKI in Neonatology

    Directory of Open Access Journals (Sweden)

    M. Mussap

    2014-01-01

    Full Text Available Identification of novel drug-induced toxic nephropathy and acute kidney injury (AKI biomarkers has been designated as a top priority by the American Society of Nephrology. Increasing knowledge in the science of biology and medicine is leading to the discovery of still more new biomarkers and of their roles in molecular pathways triggered by physiological and pathological conditions. Concomitantly, the development of the so-called “omics” allows the progressive clinical utilization of a multitude of information, from those related to the human genome (genomics and proteome (proteomics, including the emerging epigenomics, to those related to metabolites (metabolomics. In preterm newborns, one of the most important factors causing the pathogenesis and the progression of AKI is the interaction between the individual genetic code, the environment, the gestational age, and the disease. By analyzing a small urine sample, metabolomics allows to identify instantly any change in phenotype, including changes due to genetic modifications. The role of liquid chromatography-mass spectrometry (LC-MS, proton nuclear magnetic resonance (1H NMR, and other emerging technologies is strategic, contributing basically to the sudden development of new biochemical and molecular tests. Urine neutrophil gelatinase-associated lipocalin (uNGAL and kidney injury molecule-1 (KIM-1 are closely correlated with the severity of kidney injury, representing noninvasive sensitive surrogate biomarkers for diagnosing, monitoring, and quantifying kidney damage. To become routine tests, uNGAL and KIM-1 should be carefully tested in multicenter clinical trials and should be measured in biological fluids by robust, standardized analytical methods.

  8. Blood DNA methylation biomarkers predict clinical reactivity in food-sensitized infants.

    Science.gov (United States)

    Martino, David; Dang, Thanh; Sexton-Oates, Alexandra; Prescott, Susan; Tang, Mimi L K; Dharmage, Shyamali; Gurrin, Lyle; Koplin, Jennifer; Ponsonby, Anne-Louise; Allen, Katrina J; Saffery, Richard

    2015-05-01

    The diagnosis of food allergy (FA) can be challenging because approximately half of food-sensitized patients are asymptomatic. Current diagnostic tests are excellent makers of sensitization but poor predictors of clinical reactivity. Thus oral food challenges (OFCs) are required to determine a patient's risk of reactivity. We sought to discover genomic biomarkers of clinical FA with utility for predicting food challenge outcomes. Genome-wide DNA methylation (DNAm) profiling was performed on blood mononuclear cells from volunteers who had undergone objective OFCs, concurrent skin prick tests, and specific IgE tests. Fifty-eight food-sensitized patients (aged 11-15 months) were assessed, half of whom were clinically reactive. Thirteen nonallergic control subjects were also assessed. Reproducibility was assessed in an additional 48 samples by using methylation data from an independent population of patients with clinical FA. Using a supervised learning approach, we discovered a DNAm signature of 96 CpG sites that predict clinical outcomes. Diagnostic scores were derived from these 96 methylation sites, and cutoffs were determined in a sensitivity analysis. Methylation biomarkers outperformed allergen-specific IgE and skin prick tests for predicting OFC outcomes. FA status was correctly predicted in the replication cohort with an accuracy of 79.2%. DNAm biomarkers with clinical utility for predicting food challenge outcomes are readily detectable in blood. The development of this technology in detailed follow-up studies will yield highly innovative diagnostic assays. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  9. Quantification of the heterogeneity of prognostic cellular biomarkers in ewing sarcoma using automated image and random survival forest analysis.

    Directory of Open Access Journals (Sweden)

    Claudia Bühnemann

    Full Text Available Driven by genomic somatic variation, tumour tissues are typically heterogeneous, yet unbiased quantitative methods are rarely used to analyse heterogeneity at the protein level. Motivated by this problem, we developed automated image segmentation of images of multiple biomarkers in Ewing sarcoma to generate distributions of biomarkers between and within tumour cells. We further integrate high dimensional data with patient clinical outcomes utilising random survival forest (RSF machine learning. Using material from cohorts of genetically diagnosed Ewing sarcoma with EWSR1 chromosomal translocations, confocal images of tissue microarrays were segmented with level sets and watershed algorithms. Each cell nucleus and cytoplasm were identified in relation to DAPI and CD99, respectively, and protein biomarkers (e.g. Ki67, pS6, Foxo3a, EGR1, MAPK localised relative to nuclear and cytoplasmic regions of each cell in order to generate image feature distributions. The image distribution features were analysed with RSF in relation to known overall patient survival from three separate cohorts (185 informative cases. Variation in pre-analytical processing resulted in elimination of a high number of non-informative images that had poor DAPI localisation or biomarker preservation (67 cases, 36%. The distribution of image features for biomarkers in the remaining high quality material (118 cases, 104 features per case were analysed by RSF with feature selection, and performance assessed using internal cross-validation, rather than a separate validation cohort. A prognostic classifier for Ewing sarcoma with low cross-validation error rates (0.36 was comprised of multiple features, including the Ki67 proliferative marker and a sub-population of cells with low cytoplasmic/nuclear ratio of CD99. Through elimination of bias, the evaluation of high-dimensionality biomarker distribution within cell populations of a tumour using random forest analysis in quality

  10. Quantification of the heterogeneity of prognostic cellular biomarkers in ewing sarcoma using automated image and random survival forest analysis.

    Science.gov (United States)

    Bühnemann, Claudia; Li, Simon; Yu, Haiyue; Branford White, Harriet; Schäfer, Karl L; Llombart-Bosch, Antonio; Machado, Isidro; Picci, Piero; Hogendoorn, Pancras C W; Athanasou, Nicholas A; Noble, J Alison; Hassan, A Bassim

    2014-01-01

    Driven by genomic somatic variation, tumour tissues are typically heterogeneous, yet unbiased quantitative methods are rarely used to analyse heterogeneity at the protein level. Motivated by this problem, we developed automated image segmentation of images of multiple biomarkers in Ewing sarcoma to generate distributions of biomarkers between and within tumour cells. We further integrate high dimensional data with patient clinical outcomes utilising random survival forest (RSF) machine learning. Using material from cohorts of genetically diagnosed Ewing sarcoma with EWSR1 chromosomal translocations, confocal images of tissue microarrays were segmented with level sets and watershed algorithms. Each cell nucleus and cytoplasm were identified in relation to DAPI and CD99, respectively, and protein biomarkers (e.g. Ki67, pS6, Foxo3a, EGR1, MAPK) localised relative to nuclear and cytoplasmic regions of each cell in order to generate image feature distributions. The image distribution features were analysed with RSF in relation to known overall patient survival from three separate cohorts (185 informative cases). Variation in pre-analytical processing resulted in elimination of a high number of non-informative images that had poor DAPI localisation or biomarker preservation (67 cases, 36%). The distribution of image features for biomarkers in the remaining high quality material (118 cases, 104 features per case) were analysed by RSF with feature selection, and performance assessed using internal cross-validation, rather than a separate validation cohort. A prognostic classifier for Ewing sarcoma with low cross-validation error rates (0.36) was comprised of multiple features, including the Ki67 proliferative marker and a sub-population of cells with low cytoplasmic/nuclear ratio of CD99. Through elimination of bias, the evaluation of high-dimensionality biomarker distribution within cell populations of a tumour using random forest analysis in quality controlled tumour

  11. Phase II cancer clinical trials for biomarker-guided treatments.

    Science.gov (United States)

    Jung, Sin-Ho

    2018-01-01

    The design and analysis of cancer clinical trials with biomarker depend on various factors, such as the phase of trials, the type of biomarker, whether the used biomarker is validated or not, and the study objectives. In this article, we demonstrate the design and analysis of two Phase II cancer clinical trials, one with a predictive biomarker and the other with an imaging prognostic biomarker. Statistical testing methods and their sample size calculation methods are presented for each trial. We assume that the primary endpoint of these trials is a time to event variable, but this concept can be used for any type of endpoint.

  12. Genome-derived vaccines.

    Science.gov (United States)

    De Groot, Anne S; Rappuoli, Rino

    2004-02-01

    Vaccine research entered a new era when the complete genome of a pathogenic bacterium was published in 1995. Since then, more than 97 bacterial pathogens have been sequenced and at least 110 additional projects are now in progress. Genome sequencing has also dramatically accelerated: high-throughput facilities can draft the sequence of an entire microbe (two to four megabases) in 1 to 2 days. Vaccine developers are using microarrays, immunoinformatics, proteomics and high-throughput immunology assays to reduce the truly unmanageable volume of information available in genome databases to a manageable size. Vaccines composed by novel antigens discovered from genome mining are already in clinical trials. Within 5 years we can expect to see a novel class of vaccines composed by genome-predicted, assembled and engineered T- and Bcell epitopes. This article addresses the convergence of three forces--microbial genome sequencing, computational immunology and new vaccine technologies--that are shifting genome mining for vaccines onto the forefront of immunology research.

  13. The Banana Genome Hub

    Science.gov (United States)

    Droc, Gaëtan; Larivière, Delphine; Guignon, Valentin; Yahiaoui, Nabila; This, Dominique; Garsmeur, Olivier; Dereeper, Alexis; Hamelin, Chantal; Argout, Xavier; Dufayard, Jean-François; Lengelle, Juliette; Baurens, Franc-Christophe; Cenci, Alberto; Pitollat, Bertrand; D’Hont, Angélique; Ruiz, Manuel; Rouard, Mathieu; Bocs, Stéphanie

    2013-01-01

    Banana is one of the world’s favorite fruits and one of the most important crops for developing countries. The banana reference genome sequence (Musa acuminata) was recently released. Given the taxonomic position of Musa, the completed genomic sequence has particular comparative value to provide fresh insights about the evolution of the monocotyledons. The study of the banana genome has been enhanced by a number of tools and resources that allows harnessing its sequence. First, we set up essential tools such as a Community Annotation System, phylogenomics resources and metabolic pathways. Then, to support post-genomic efforts, we improved banana existing systems (e.g. web front end, query builder), we integrated available Musa data into generic systems (e.g. markers and genetic maps, synteny blocks), we have made interoperable with the banana hub, other existing systems containing Musa data (e.g. transcriptomics, rice reference genome, workflow manager) and finally, we generated new results from sequence analyses (e.g. SNP and polymorphism analysis). Several uses cases illustrate how the Banana Genome Hub can be used to study gene families. Overall, with this collaborative effort, we discuss the importance of the interoperability toward data integration between existing information systems. Database URL: http://banana-genome.cirad.fr/ PMID:23707967

  14. Genomic instability following irradiation

    International Nuclear Information System (INIS)

    Hacker-Klom, U.B.; Goehde, W.

    2001-01-01

    Ionising irradiation may induce genomic instability. The broad spectrum of stress reactions in eukaryontic cells to irradiation complicates the discovery of cellular targets and pathways inducing genomic instability. Irradiation may initiate genomic instability by deletion of genes controlling stability, by induction of genes stimulating instability and/or by activating endogeneous cellular viruses. Alternatively or additionally it is discussed that the initiation of genomic instability may be a consequence of radiation or other agents independently of DNA damage implying non nuclear targets, e.g. signal cascades. As a further mechanism possibly involved our own results may suggest radiation-induced changes in chromatin structure. Once initiated the process of genomic instability probably is perpetuated by endogeneous processes necessary for proliferation. Genomic instability may be a cause or a consequence of the neoplastic phenotype. As a conclusion from the data available up to now a new interpretation of low level radiation effects for radiation protection and in radiotherapy appears useful. The detection of the molecular mechanisms of genomic instability will be important in this context and may contribute to a better understanding of phenomenons occurring at low doses <10 cSv which are not well understood up to now. (orig.)

  15. Discovering biomarkers for antidepressant response: protocol from the Canadian biomarker integration network in depression (CAN-BIND) and clinical characteristics of the first patient cohort.

    Science.gov (United States)

    Lam, Raymond W; Milev, Roumen; Rotzinger, Susan; Andreazza, Ana C; Blier, Pierre; Brenner, Colleen; Daskalakis, Zafiris J; Dharsee, Moyez; Downar, Jonathan; Evans, Kenneth R; Farzan, Faranak; Foster, Jane A; Frey, Benicio N; Geraci, Joseph; Giacobbe, Peter; Feilotter, Harriet E; Hall, Geoffrey B; Harkness, Kate L; Hassel, Stefanie; Ismail, Zahinoor; Leri, Francesco; Liotti, Mario; MacQueen, Glenda M; McAndrews, Mary Pat; Minuzzi, Luciano; Müller, Daniel J; Parikh, Sagar V; Placenza, Franca M; Quilty, Lena C; Ravindran, Arun V; Salomons, Tim V; Soares, Claudio N; Strother, Stephen C; Turecki, Gustavo; Vaccarino, Anthony L; Vila-Rodriguez, Fidel; Kennedy, Sidney H

    2016-04-16

    Major Depressive Disorder (MDD) is among the most prevalent and disabling medical conditions worldwide. Identification of clinical and biological markers ("biomarkers") of treatment response could personalize clinical decisions and lead to better outcomes. This paper describes the aims, design, and methods of a discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). The CAN-BIND research program investigates and identifies biomarkers that help to predict outcomes in patients with MDD treated with antidepressant medication. The primary objective of this initial study (known as CAN-BIND-1) is to identify individual and integrated neuroimaging, electrophysiological, molecular, and clinical predictors of response to sequential antidepressant monotherapy and adjunctive therapy in MDD. CAN-BIND-1 is a multisite initiative involving 6 academic health centres working collaboratively with other universities and research centres. In the 16-week protocol, patients with MDD are treated with a first-line antidepressant (escitalopram 10-20 mg/d) that, if clinically warranted after eight weeks, is augmented with an evidence-based, add-on medication (aripiprazole 2-10 mg/d). Comprehensive datasets are obtained using clinical rating scales; behavioural, dimensional, and functioning/quality of life measures; neurocognitive testing; genomic, genetic, and proteomic profiling from blood samples; combined structural and functional magnetic resonance imaging; and electroencephalography. De-identified data from all sites are aggregated within a secure neuroinformatics platform for data integration, management, storage, and analyses. Statistical analyses will include multivariate and machine-learning techniques to identify predictors, moderators, and mediators of treatment response. From June 2013 to February 2015, a cohort of 134 participants (85 outpatients with MDD and 49 healthy participants

  16. Predictive biomarkers for type 2 of diabetes mellitus: Bridging the gap between systems research and personalized medicine.

    Science.gov (United States)

    Kraniotou, Christina; Karadima, Vasiliki; Bellos, George; Tsangaris, George Th

    2018-03-05

    The global incidence of metabolic disorders like type 2 diabetes mellitus (DM2) has assumed epidemic proportions, leading to adverse health and socio-economic impacts. It is therefore of critical importance the early diagnosis of DM2 patients and the detection of those at increased risk of disease. In this respect, Precision Medicine (PM) is an emerging approach that includes practices, tests, decisions and treatments adapted to the characteristics of each patient. With regard to DM2, PM manages a wealth of "omics" data (genomic, metabolic, proteomic, environmental, clinical and paraclinical) to increase the number of clinically validated biomarkers in order to identify patients in early stage even before the prediabetic phase. In this paper, we discuss the epidemic dimension of metabolic disorders like type 2 diabetes mellitus (DM2) and the urgent demand for novel biomarkers to reduce the incidence or even delay the onset of DM2. Recent research data produced by "multi-omics" technologies (genomics/epigenomics, transcriptomics, proteomics and metabolomics), suggest that many potential biomarkers might be helpful in the prediction and early diagnosis of DM2. Predictive, Preventive and Personalized Medicine (PPPM) manages and integrates these data to apply personalized, preventive, and therapeutic approaches. This is significant because there is an emerging need for establishing channels for communication and personalized consultation between systems research and precision medicine, as the medicine of the future. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Epigenetic regulation of ageing: linking environmental inputs to genomic stability

    Science.gov (United States)

    Benayoun, Bérénice A.; Pollina, Elizabeth A.; Brunet, Anne

    2016-01-01

    Preface Ageing is affected by both genetic and non-genetic factors. Here, we review the chromatin-based epigenetic changes that occur during ageing, the role of chromatin modifiers in modulating lifespan and the importance of epigenetic signatures as biomarkers of ageing. We also discuss how epigenome remodeling by environmental stimuli impacts several aspects of transcription and genomic stability, with important consequences on longevity, and outline epigenetic differences between the ‘mortal soma’ and the ‘immortal germline’. Finally, we discuss the inheritance of ageing characteristics and potential chromatin-based strategies to delay or reverse hallmarks of ageing or age-related diseases. PMID:26373265

  18. Genome-wide comparison of medieval and modern Mycobacterium leprae

    DEFF Research Database (Denmark)

    Schuenemann, Verena J; Singh, Pushpendra; Mendum, Thomas A

    2013-01-01

    Leprosy was endemic in Europe until the Middle Ages. Using DNA array capture, we have obtained genome sequences of Mycobacterium leprae from skeletons of five medieval leprosy cases from the United Kingdom, Sweden, and Denmark. In one case, the DNA was so well preserved that full de novo assembly...... origin for leprosy in the Americas, and the presence of an M. leprae genotype in medieval Europe now commonly associated with the Middle East. The exceptional preservation of M. leprae biomarkers, both DNA and mycolic acids, in ancient skeletons has major implications for palaeomicrobiology and human...

  19. Overview of Biomarkers and Surrogate Endpoints in Drug Development

    Directory of Open Access Journals (Sweden)

    John A. Wagner

    2002-01-01

    Full Text Available There are numerous factors that recommend the use of biomarkers in drug development including the ability to provide a rational basis for selection of lead compounds, as an aid in determining or refining mechanism of action or pathophysiology, and the ability to work towards qualification and use of a biomarker as a surrogate endpoint. Examples of biomarkers come from many different means of clinical and laboratory measurement. Total cholesterol is an example of a clinically useful biomarker that was successfully qualified for use as a surrogate endpoint. Biomarkers require validation in most circumstances. Validation of biomarker assays is a necessary component to delivery of high-quality research data necessary for effective use of biomarkers. Qualification is necessary for use of a biomarker as a surrogate endpoint. Putative biomarkers are typically identified because of a relationship to known or hypothetical steps in a pathophysiologic cascade. Biomarker discovery can also be effected by expression profiling experiment using a variety of array technologies and related methods. For example, expression profiling experiments enabled the discovery of adipocyte related complement protein of 30 kD (Acrp30 or adiponectin as a biomarker for in vivo activation of peroxisome proliferator-activated receptors (PPAR γ activity.

  20. More Accurate Oral Cancer Screening with Fewer Salivary Biomarkers

    Directory of Open Access Journals (Sweden)

    James Michael Menke

    2017-10-01

    Full Text Available Signal detection and Bayesian inferential tools were applied to salivary biomarkers to improve screening accuracy and efficiency in detecting oral squamous cell carcinoma (OSCC. Potential cancer biomarkers are identified by significant differences in assay concentrations, receiver operating characteristic areas under the curve (AUCs, sensitivity, and specificity. However, the end goal is to report to individual patients their risk of having disease given positive or negative test results. Likelihood ratios (LRs and Bayes factors (BFs estimate evidential support and compile biomarker information to optimize screening accuracy. In total, 26 of 77 biomarkers were mentioned as having been tested at least twice in 137 studies and published in 16 summary papers through 2014. Studies represented 10 212 OSCC and 25 645 healthy patients. The measure of biomarker and panel information value was number of biomarkers needed to approximate 100% positive predictive value (PPV. As few as 5 biomarkers could achieve nearly 100% PPV for a disease prevalence of 0.2% when biomarkers were ordered from highest to lowest LR. When sequentially interpreting biomarker tests, high specificity was more important than test sensitivity in achieving rapid convergence toward a high PPV. Biomarkers ranked from highest to lowest LR were more informative and easier to interpret than AUC or Youden index. The proposed method should be applied to more recently published biomarker data to test its screening value.

  1. Detection of biomarkers for Hepatocellular Carcinoma using a hybrid univariate gene selection methods

    Directory of Open Access Journals (Sweden)

    Abdel Samee Nagwan M

    2012-08-01

    Full Text Available Abstract Background Discovering new biomarkers has a great role in improving early diagnosis of Hepatocellular carcinoma (HCC. The experimental determination of biomarkers needs a lot of time and money. This motivates this work to use in-silico prediction of biomarkers to reduce the number of experiments required for detecting new ones. This is achieved by extracting the most representative genes in microarrays of HCC. Results In this work, we provide a method for extracting the differential expressed genes, up regulated ones, that can be considered candidate biomarkers in high throughput microarrays of HCC. We examine the power of several gene selection methods (such as Pearson’s correlation coefficient, Cosine coefficient, Euclidean distance, Mutual information and Entropy with different estimators in selecting informative genes. A biological interpretation of the highly ranked genes is done using KEGG (Kyoto Encyclopedia of Genes and Genomes pathways, ENTREZ and DAVID (Database for Annotation, Visualization, and Integrated Discovery databases. The top ten genes selected using Pearson’s correlation coefficient and Cosine coefficient contained six genes that have been implicated in cancer (often multiple cancers genesis in previous studies. A fewer number of genes were obtained by the other methods (4 genes using Mutual information, 3genes using Euclidean distance and only one gene using Entropy. A better result was obtained by the utilization of a hybrid approach based on intersecting the highly ranked genes in the output of all investigated methods. This hybrid combination yielded seven genes (2 genes for HCC and 5 genes in different types of cancer in the top ten genes of the list of intersected genes. Conclusions To strengthen the effectiveness of the univariate selection methods, we propose a hybrid approach by intersecting several of these methods in a cascaded manner. This approach surpasses all of univariate selection methods when

  2. Identifying DNA Methylation Biomarkers for Non-Endoscopic Detection of Barrett’s Esophagus

    Science.gov (United States)

    Moinova, Helen R.; LaFramboise, Thomas; Lutterbaugh, James D.; Chandar, Apoorva Krishna; Dumot, John; Faulx, Ashley; Brock, Wendy; De la Cruz Cabrera, Omar; Guda, Kishore; Barnholtz-Sloan, Jill S.; Iyer, Prasad G.; Canto, Marcia I.; Wang, Jean S.; Shaheen, Nicholas J.; Thota, Prashanti N.; Willis, Joseph E.; Chak, Amitabh; Markowitz, Sanford D.

    2018-01-01

    We report a biomarker-based non-endoscopic method for detecting Barrett’s esophagus (BE), based on detecting methylated DNAs retrieved via a swallowable balloon-based esophageal sampling device. BE is the precursor of, and a major recognized risk factor for, developing esophageal adenocarcinoma (EAC). Endoscopy, the current standard for BE detection, is not cost-effective for population screening. We performed genome-wide screening to ascertain regions targeted for recurrent aberrant cytosine methylation in BE, identifying high-frequency methylation within the CCNA1 locus. We tested CCNA1 DNA methylation as a BE biomarker in cytology brushings of the distal esophagus from 173 individuals with or without BE. CCNA1 DNA methylation demonstrated an area under the curve (AUC)=0.95 for discriminating BE-related metaplasia and neoplasia cases versus normal individuals, performing identically to methylation of VIM DNA, an established BE biomarker. When combined, the resulting two biomarker panel was 95% sensitive and 91% specific. These results were replicated in an independent validation cohort of 149 individuals, who were assayed using the same cutoff values for test positivity established in the training population. To progress toward non-endoscopic esophageal screening, we engineered a well-tolerated, swallowable, encapsulated balloon device able to selectively sample the distal esophagus within 5 minutes. In balloon samples from 86 individuals, tests of CCNA1 plus VIM DNA methylation detected BE metaplasia with 90.3% sensitivity and 91.7% specificity. Combining the balloon sampling device with molecular assays of CCNA1 plus VIM DNA methylation enables an efficient, well-tolerated, sensitive, and specific method of screening at-risk populations for BE. PMID:29343623

  3. IL-8 as a urinary biomarker for the detection of bladder cancer

    Directory of Open Access Journals (Sweden)

    Urquidi Virginia

    2012-05-01

    Full Text Available Abstract Background Current urine-based assays for bladder cancer (BCa diagnosis lack accuracy, so the search for improved biomarkers continues. Through genomic and proteomic profiling of urine, we have identified a panel of biomarkers associated with the presence of BCa. In this study, we evaluated the utility of three of these biomarkers, interleukin 8 (IL-8, Matrix metallopeptidase 9 (MMP-9 and Syndecan in the diagnosis of BCa through urinalysis. Methods Voided urines from 127 subjects, cancer subjects (n = 64, non-cancer subjects (n = 63 were analyzed. The protein concentrations of IL-8, MMP-9, and Syndecan were assessed by enzyme-linked immunosorbent assay (ELISA. Data were also compared to a commercial ELISA-based BCa detection assay (BTA-Trak© and urinary cytology. We used the area under the curve of a receiver operating characteristic (AUROC to compare the performance of each biomarker. Results Urinary protein concentrations of IL-8, MMP-9 and BTA were significantly elevated in BCa subjects. Of the experimental markers compared to BTA-Trak©, IL-8 was the most prominent marker (AUC; 0.79; 95% confidence interval [CI], 0.72-0.86. Multivariate regression analysis revealed that only IL-8 (OR; 1.51; 95% CI, 1.16-1.97, p = 0.002 was an independent factor for the detection of BCa. Conclusions These results suggest that the measurement of IL-8 in voided urinary samples may have utility for urine-based detection of BCa. These findings need to be confirmed in a larger, prospective cohort.

  4. The path from biomarker discovery to regulatory qualification

    CERN Document Server

    Goodsaid, Federico

    2013-01-01

    The Path from Biomarker Discovery to Regulatory Qualification is a unique guide that focuses on biomarker qualification, its history and current regulatory settings in both the US and abroad. This multi-contributed book provides a detailed look at the next step to developing biomarkers for clinical use and covers overall concepts, challenges, strategies and solutions based on the experiences of regulatory authorities and scientists. Members of the regulatory, pharmaceutical and biomarker development communities will benefit the most from using this book-it is a complete and practical guide to biomarker qualification, providing valuable insight to an ever-evolving and important area of regulatory science. For complimentary access to chapter 13, 'Classic' Biomarkers of Liver Injury, by John R. Senior, Associate Director for Science, Food and Drug Administration, Silver Spring, Maryland, USA, please visit the following site:  http://tinyurl.com/ClassicBiomarkers Contains a collection of experiences of different...

  5. Biomarkers of intermediate endpoints in environmental and occupational health

    DEFF Research Database (Denmark)

    Knudsen, Lisbeth E; Hansen, Ase M

    2007-01-01

    The use of biomarkers in environmental and occupational health is increasing due to increasing demands on information about health risks from unfavourable exposures. Biomarkers provide information about individual loads. Biomarkers of intermediate endpoints benefit in comparison with biomarkers...... of exposure from the fact that they are closer to the adverse outcome in the pathway from exposure to health effects and may provide powerful information for intervention. Some biomarkers are specific, e.g., DNA and protein adducts, while others are unspecific like the cytogenetic biomarkers of chromosomal...... health effect from the result of the measurement has been performed for the cytogenetic biomarkers showing a predictive value of high levels of CA and increased risk of cancer. The use of CA in future studies is, however, limited by the laborious and sensitive procedure of the test and lack of trained...

  6. Traditional medicine and genomics

    Directory of Open Access Journals (Sweden)

    Kalpana Joshi

    2010-01-01

    Full Text Available ′Omics′ developments in the form of genomics, proteomics and metabolomics have increased the impetus of traditional medicine research. Studies exploring the genomic, proteomic and metabolomic basis of human constitutional types based on Ayurveda and other systems of oriental medicine are becoming popular. Such studies remain important to developing better understanding of human variations and individual differences. Countries like India, Korea, China and Japan are investing in research on evidence-based traditional medicines and scientific validation of fundamental principles. This review provides an account of studies addressing relationships between traditional medicine and genomics.

  7. Traditional medicine and genomics.

    Science.gov (United States)

    Joshi, Kalpana; Ghodke, Yogita; Shintre, Pooja

    2010-01-01

    'Omics' developments in the form of genomics, proteomics and metabolomics have increased the impetus of traditional medicine research. Studies exploring the genomic, proteomic and metabolomic basis of human constitutional types based on Ayurveda and other systems of oriental medicine are becoming popular. Such studies remain important to developing better understanding of human variations and individual differences. Countries like India, Korea, China and Japan are investing in research on evidence-based traditional medicines and scientific validation of fundamental principles. This review provides an account of studies addressing relationships between traditional medicine and genomics.

  8. Bacillus subtilis genome diversity.

    Science.gov (United States)

    Earl, Ashlee M; Losick, Richard; Kolter, Roberto

    2007-02-01

    Microarray-based comparative genomic hybridization (M-CGH) is a powerful method for rapidly identifying regions of genome diversity among closely related organisms. We used M-CGH to examine the genome diversity of 17 strains belonging to the nonpathogenic species Bacillus subtilis. Our M-CGH results indicate that there is considerable genetic heterogeneity among members of this species; nearly one-third of Bsu168-specific genes exhibited variability, as measured by the microarray hybridization intensities. The variable loci include those encoding proteins involved in antibiotic production, cell wall synthesis, sporulation, and germination. The diversity in these genes may reflect this organism's ability to survive in diverse natural settings.

  9. Genomic taxonomy of vibrios

    Directory of Open Access Journals (Sweden)

    Iida Tetsuya

    2009-10-01

    Full Text Available Abstract Background Vibrio taxonomy has been based on a polyphasic approach. In this study, we retrieve useful taxonomic information (i.e. data that can be used to distinguish different taxonomic levels, such as species and genera from 32 genome sequences of different vibrio species. We use a variety of tools to explore the taxonomic relationship between the sequenced genomes, including Multilocus Sequence Analysis (MLSA, supertrees, Average Amino Acid Identity (AAI, genomic signatures, and Genome BLAST atlases. Our aim is to analyse the usefulness of these tools for species identification in vibrios. Results We have generated four new genome sequences of three Vibrio species, i.e., V. alginolyticus 40B, V. harveyi-like 1DA3, and V. mimicus strains VM573 and VM603, and present a broad analyses of these genomes along with other sequenced Vibrio species. The genome atlas and pangenome plots provide a tantalizing image of the genomic differences that occur between closely related sister species, e.g. V. cholerae and V. mimicus. The vibrio pangenome contains around 26504 genes. The V. cholerae core genome and pangenome consist of 1520 and 6923 genes, respectively. Pangenomes might allow different strains of V. cholerae to occupy different niches. MLSA and supertree analyses resulted in a similar phylogenetic picture, with a clear distinction of four groups (Vibrio core group, V. cholerae-V. mimicus, Aliivibrio spp., and Photobacterium spp.. A Vibrio species is defined as a group of strains that share > 95% DNA identity in MLSA and supertree analysis, > 96% AAI, ≤ 10 genome signature dissimilarity, and > 61% proteome identity. Strains of the same species and species of the same genus will form monophyletic groups on the basis of MLSA and supertree. Conclusion The combination of different analytical and bioinformatics tools will enable the most accurate species identification through genomic computational analysis. This endeavour will culminate in

  10. Human Genome Project

    Energy Technology Data Exchange (ETDEWEB)

    Block, S. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Cornwall, J. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Dally, W. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Dyson, F. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Fortson, N. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Joyce, G. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Kimble, H. J. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Lewis, N. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Max, C. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Prince, T. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Schwitters, R. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Weinberger, P. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Woodin, W. H. [The MITRE Corporation, McLean, VA (US). JASON Program Office

    1998-01-04

    The study reviews Department of Energy supported aspects of the United States Human Genome Project, the joint National Institutes of Health/Department of Energy program to characterize all human genetic material, to discover the set of human genes, and to render them accessible for further biological study. The study concentrates on issues of technology, quality assurance/control, and informatics relevant to current effort on the genome project and needs beyond it. Recommendations are presented on areas of the genome program that are of particular interest to and supported by the Department of Energy.

  11. Human Genome Program

    Energy Technology Data Exchange (ETDEWEB)

    1993-01-01

    The DOE Human Genome program has grown tremendously, as shown by the marked increase in the number of genome-funded projects since the last workshop held in 1991. The abstracts in this book describe the genome research of DOE-funded grantees and contractors and invited guests, and all projects are represented at the workshop by posters. The 3-day meeting includes plenary sessions on ethical, legal, and social issues pertaining to the availability of genetic data; sequencing techniques, informatics support; and chromosome and cDNA mapping and sequencing.

  12. Genomic signal processing

    CERN Document Server

    Shmulevich, Ilya

    2007-01-01

    Genomic signal processing (GSP) can be defined as the analysis, processing, and use of genomic signals to gain biological knowledge, and the translation of that knowledge into systems-based applications that can be used to diagnose and treat genetic diseases. Situated at the crossroads of engineering, biology, mathematics, statistics, and computer science, GSP requires the development of both nonlinear dynamical models that adequately represent genomic regulation, and diagnostic and therapeutic tools based on these models. This book facilitates these developments by providing rigorous mathema

  13. Epigenetics of obesity: beyond the genome sequence.

    Science.gov (United States)

    Cordero, Paul; Li, Jiawei; Oben, Jude A

    2015-07-01

    After the study of the gene code as a trigger for obesity, epigenetic code has appeared as a novel tool in the diagnosis, prognosis and treatment of obesity, and its related comorbidities. This review summarizes the status of the epigenetic field associated with obesity, and the current epigenetic-based approaches for obesity treatment. Thanks to technical advances, novel and key obesity-associated polymorphisms have been described by genome-wide association studies, but there are limitations with their predictive power. Epigenetics is also studied for disease association, which involves decoding of the genome information, transcriptional status and later phenotypes. Obesity could be induced during adult life by feeding and other environmental factors, and there is a strong association between obesity features and specific epigenetic patterns. These patterns could be established during early life stages, and programme the risk of obesity and its comorbidities during adult life. Furthermore, recent studies have shown that DNA methylation profile could be applied as biomarkers of diet-induced weight loss treatment. High-throughput technologies, recently implemented for commercial genetic test panels, could soon lead to the creation of epigenetic test panels for obesity. Nonetheless, epigenetics is a modifiable risk factor, and different dietary patterns or environmental insights during distinct stages of life could lead to rewriting of the epigenetic profile.

  14. Traumatic brain injury produced by exposure to blasts, a critical problem in current wars: biomarkers, clinical studies, and animal models

    Science.gov (United States)

    Dixon, C. Edward

    2011-06-01

    Traumatic brain injury (TBI) resulting from exposure to blast energy released by Improvised Explosive Devices (IEDs) has been recognized as the "signature injury" of Operation Iraqi Freedom and Operation Enduring Freedom. Repeated exposure to mild blasts may produce subtle deficits that are difficult to detect and quantify. Several techniques have been used to detect subtle brain dysfunction including neuropsychological assessments, computerized function testing and neuroimaging. Another approach is based on measurement of biologic substances (e.g. proteins) that are released into the body after a TBI. Recent studies measuring biomarkers in CSF and serum from patients with severe TBI have demonstrated the diagnostic, prognostic, and monitoring potential. Advancement of the field will require 1) biochemical mining for new biomarker candidates, 2) clinical validation of utility, 3) technical advances for more sensitive, portable detectors, 4) novel statistical approach to evaluate multiple biomarkers, and 5) commercialization. Animal models have been developed to simulate elements of blast-relevant TBI including gas-driven shock tubes to generate pressure waves similar to those produced by explosives. These models can reproduce hallmark clinical neuropathological responses such as neuronal degeneration and inflammation, as well as behavioral impairments. An important application of these models is to screen novel therapies and conduct proteomic, genomic, and lipodomic studies to mine for new biomarker candidates specific to blast relevant TBI.

  15. Genomics and fish adaptation

    Directory of Open Access Journals (Sweden)

    Agostinho Antunes

    2015-12-01

    Full Text Available The completion of the human genome sequencing in 2003 opened a new perspective into the importance of whole genome sequencing projects, and currently multiple species are having their genomes completed sequenced, from simple organisms, such as bacteria, to more complex taxa, such as mammals. This voluminous sequencing data generated across multiple organisms provides also the framework to better understand the genetic makeup of such species and related ones, allowing to explore the genetic changes underlining the evolution of diverse phenotypic traits. Here, recent results from our group retrieved from comparative evolutionary genomic analyses of varied fish species will be considered to exemplify how gene novelty and gene enhancement by positive selection might have been determinant in the success of adaptive radiations into diverse habitats and lifestyles.

  16. Lophotrochozoan mitochondrial genomes

    Energy Technology Data Exchange (ETDEWEB)

    Valles, Yvonne; Boore, Jeffrey L.

    2005-10-01

    Progress in both molecular techniques and phylogeneticmethods has challenged many of the interpretations of traditionaltaxonomy. One example is in the recognition of the animal superphylumLophotrochozoa (annelids, mollusks, echiurans, platyhelminthes,brachiopods, and other phyla), although the relationships within thisgroup and the inclusion of some phyla remain uncertain. While much ofthis progress in phylogenetic reconstruction has been based on comparingsingle gene sequences, we are beginning to see the potential of comparinglarge-scale features of genomes, such as the relative order of genes.Even though tremendous progress is being made on the sequencedetermination of whole nuclear genomes, the dataset of choice forgenome-level characters for many animals across a broad taxonomic rangeremains mitochondrial genomes. We review here what is known aboutmitochondrial genomes of the lophotrochozoans and discuss the promisethat this dataset will enable insight into theirrelationships.

  17. Mouse Genome Informatics (MGI)

    Data.gov (United States)

    U.S. Department of Health & Human Services — MGI is the international database resource for the laboratory mouse, providing integrated genetic, genomic, and biological data to facilitate the study of human...

  18. Genomic definition of species

    Energy Technology Data Exchange (ETDEWEB)

    Crkvenjakov, R.; Drmanac, R.

    1991-07-01

    The subject of this paper is the definition of species based on the assumption that genome is the fundamental level for the origin and maintenance of biological diversity. For this view to be logically consistent it is necessary to assume the existence and operation of the new law which we call genome law. For this reason the genome law is included in the explanation of species phenomenon presented here even if its precise formulation and elaboration are left for the future. The intellectual underpinnings of this definition can be traced to Goldschmidt. We wish to explore some philosophical aspects of the definition of species in terms of the genome. The point of proposing the definition on these grounds is that any real advance in evolutionary theory has to be correct in both its philosophy and its science.

  19. Structural genomics in endocrinology

    NARCIS (Netherlands)

    Smit, J. W.; Romijn, J. A.

    2001-01-01

    Traditionally, endocrine research evolved from the phenotypical characterisation of endocrine disorders to the identification of underlying molecular pathophysiology. This approach has been, and still is, extremely successful. The introduction of genomics and proteomics has resulted in a reversal of

  20. Epidemiology & Genomics Research Program

    Science.gov (United States)

    The Epidemiology and Genomics Research Program, in the National Cancer Institute's Division of Cancer Control and Population Sciences, funds research in human populations to understand the determinants of cancer occurrence and outcomes.

  1. Annotating individual human genomes.

    Science.gov (United States)

    Torkamani, Ali; Scott-Van Zeeland, Ashley A; Topol, Eric J; Schork, Nicholas J

    2011-10-01

    Advances in DNA sequencing technologies have made it possible to rapidly, accurately and affordably sequence entire individual human genomes. As impressive as this ability seems, however, it will not likely amount to much if one cannot extract meaningful information from individual sequence data. Annotating variations within individual genomes and providing information about their biological or phenotypic impact will thus be crucially important in moving individual sequencing projects forward, especially in the context of the clinical use of sequence information. In this paper we consider the various ways in which one might annotate individual sequence variations and point out limitations in the available methods for doing so. It is arguable that, in the foreseeable future, DNA sequencing of individual genomes will become routine for clinical, research, forensic, and personal purposes. We therefore also consider directions and areas for further research in annotating genomic variants. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. ANNOTATING INDIVIDUAL HUMAN GENOMES*

    Science.gov (United States)

    Torkamani, Ali; Scott-Van Zeeland, Ashley A.; Topol, Eric J.; Schork, Nicholas J.

    2014-01-01

    Advances in DNA sequencing technologies have made it possible to rapidly, accurately and affordably sequence entire individual human genomes. As impressive as this ability seems, however, it will not likely to amount to much if one cannot extract meaningful information from individual sequence data. Annotating variations within individual genomes and providing information about their biological or phenotypic impact will thus be crucially important in moving individual sequencing projects forward, especially in the context of the clinical use of sequence information. In this paper we consider the various ways in which one might annotate individual sequence variations and point out limitations in the available methods for doing so. It is arguable that, in the foreseeable future, DNA sequencing of individual genomes will become routine for clinical, research, forensic, and personal purposes. We therefore also consider directions and areas for further research in annotating genomic variants. PMID:21839162

  3. Yeast genome sequencing:

    DEFF Research Database (Denmark)

    Piskur, Jure; Langkjær, Rikke Breinhold

    2004-01-01

    For decades, unicellular yeasts have been general models to help understand the eukaryotic cell and also our own biology. Recently, over a dozen yeast genomes have been sequenced, providing the basis to resolve several complex biological questions. Analysis of the novel sequence data has shown...... of closely related species helps in gene annotation and to answer how many genes there really are within the genomes. Analysis of non-coding regions among closely related species has provided an example of how to determine novel gene regulatory sequences, which were previously difficult to analyse because...... they are short and degenerate and occupy different positions. Comparative genomics helps to understand the origin of yeasts and points out crucial molecular events in yeast evolutionary history, such as whole-genome duplication and horizontal gene transfer(s). In addition, the accumulating sequence data provide...

  4. Genetical Genomics for Evolutionary Studies

    NARCIS (Netherlands)

    Prins, J.C.P.; Smant, G.; Jansen, R.C.

    2012-01-01

    Genetical genomics combines acquired high-throughput genomic data with genetic analysis. In this chapter, we discuss the application of genetical genomics for evolutionary studies, where new high-throughput molecular technologies are combined with mapping quantitative trait loci (QTL) on the genome

  5. Molecular alterations and biomarkers in colorectal cancer

    Science.gov (United States)

    Grady, William M.; Pritchard, Colin C.

    2013-01-01

    The promise of precision medicine is now a clinical reality. Advances in our understanding of the molecular genetics of colorectal cancer genetics is leading to the development of a variety of biomarkers that are being used as early detection markers, prognostic markers, and markers for predicting treatment responses. This is no more evident than in the recent advances in testing colorectal cancers for specific molecular alterations in order to guide treatment with the monoclonal antibody therapies cetuximab and panitumumab, which target the epidermal growth factor receptor (EGFR). In this review, we update a prior review published in 2010 and describe our current understanding of the molecular pathogenesis of colorectal cancer and how these alterations relate to emerging biomarkers for early detection and risk stratification (diagnostic markers), prognosis (prognostic markers), and the prediction of treatment responses (predictive markers). PMID:24178577

  6. Flavonoids as fruit and vegetable intake biomarkers

    DEFF Research Database (Denmark)

    Krogholm, Kirstine Suszkiewicz

    of fruit and vegetable intakes. In Paper I, the urinary recovery of the 7 flavonoids in morning spot urine (i.e. all urine voids from midnight including the first morning void) was also found to respond to moderate increases in the intake of fruits and vegetables. However, the association was somewhat...... weaker than in 24h urine samples, indicating that the 24h urinary recovery of the 7 flavonoids is a stronger biomarker of the intake of fruit and vegetables than the urinary recovery of the 7 flavonoids in morning spot urine. In Paper II, the biokinetic profiles of some of the most important dietary......-individual variation in the absorption and urinary recovery of the flavonoids, and this makes it very difficult to separate individuals according to intake by use of the flavonoid biomarker in urine. The intra-individual variation was on the contrary low, and Paper II therefore supports the assumption, that 24h...

  7. Mass Spectrometry-Based Biomarker Discovery.

    Science.gov (United States)

    Zhou, Weidong; Petricoin, Emanuel F; Longo, Caterina

    2017-01-01

    The discovery of candidate biomarkers within the entire proteome is one of the most important and challenging goals in proteomic research. Mass spectrometry-based proteomics is a modern and promising technology for semiquantitative and qualitative assessment of proteins, enabling protein sequencing and identification with exquisite accuracy and sensitivity. For mass spectrometry analysis, protein extractions from tissues or body fluids and subsequent protein fractionation represent an important and unavoidable step in the workflow for biomarker discovery. Following extraction of proteins, the protein mixture must be digested, reduced, alkylated, and cleaned up prior to mass spectrometry. The aim of our chapter is to provide comprehensible and practical lab procedures for sample digestion, protein fractionation, and subsequent mass spectrometry analysis.

  8. Methylated genes as new cancer biomarkers.

    LENUS (Irish Health Repository)

    Duffy, M J

    2012-02-01

    Aberrant hypermethylation of promoter regions in specific genes is a key event in the formation and progression of cancer. In at least some situations, these aberrant alterations occur early in the formation of malignancy and appear to be tumour specific. Multiple reports have suggested that measurement of the methylation status of the promoter regions of specific genes can aid early detection of cancer, determine prognosis and predict therapy responses. Promising DNA methylation biomarkers include the use of methylated GSTP1 for aiding the early diagnosis of prostate cancer, methylated PITX2 for predicting outcome in lymph node-negative breast cancer patients and methylated MGMT in predicting benefit from alkylating agents in patients with glioblastomas. However, prior to clinical utilisation, these findings require validation in prospective clinical studies. Furthermore, assays for measuring gene methylation need to be standardised, simplified and evaluated in external quality assurance programmes. It is concluded that methylated genes have the potential to provide a new generation of cancer biomarkers.

  9. Models of Hepatocellular Carcinoma and Biomarker Strategy

    Energy Technology Data Exchange (ETDEWEB)

    Bagi, Cedo M., E-mail: cedo.bagi@pfizer.com; Andresen, Catharine J. [Global Science & Technology, PGRD, Pfizer Inc, Groton, CT 06340 (United States)

    2010-07-07

    The overwhelming need to improve preclinical models in oncology has stimulated research efforts to refine and validate robust orthotopic models that closely mimic the disease population and therefore have the potential to better predict clinical outcome with novel therapies. Sophisticated technologies including bioluminescence, contrast enhanced ultrasound imaging, positron emission tomography, computed tomography and magnetic resonance imaging have been added to existing serum- and histology-based biomarkers to assist with patient selection and the design of clinical trials. The rationale for the use of human hepatocellular carcinoma (HCC) cell lines, implementation of xenograft and orthotopic animal models and utilization of available biomarkers have been discussed, providing guidelines to facilitate preclinical research for the development of treatments for HCC patients.

  10. Flavonoids as fruit and vegetable intake biomarkers

    DEFF Research Database (Denmark)

    Krogholm, Kirstine Suszkiewicz

    calculation of the bivariate correlation coefficients is the common approach when using only one reference method. Back in 2002, a strictly controlled dietary intervention study indicated that the sum of 7 different flavonoid aglycones excreted in 24h urine samples potentially could be used as a biomarker...... and cohort studies. The Ph.D. thesis contains four scientific papers. Paper I provides evidence that the sum of 7 flavonoids in 24h urine respond in a linear and sensitive manner to moderate increases in the intake of fruits and vegetables, and thus consolidates that the flavonoids are a valid biomarker...... of fruit and vegetable intakes. In Paper I, the urinary recovery of the 7 flavonoids in morning spot urine (i.e. all urine voids from midnight including the first morning void) was also found to respond to moderate increases in the intake of fruits and vegetables. However, the association was somewhat...

  11. Microparticles as Potential Biomarkers of Cardiovascular Disease

    International Nuclear Information System (INIS)

    França, Carolina Nunes; Izar, Maria Cristina de Oliveira; Amaral, Jônatas Bussador do; Tegani, Daniela Melo; Fonseca, Francisco Antonio Helfenstein

    2015-01-01

    Primary prevention of cardiovascular disease is a choice of great relevance because of its impact on health. Some biomarkers, such as microparticles derived from different cell populations, have been considered useful in the assessment of cardiovascular disease. Microparticles are released by the membrane structures of different cell types upon activation or apoptosis, and are present in the plasma of healthy individuals (in levels considered physiological) and in patients with different pathologies. Many studies have suggested an association between microparticles and different pathological conditions, mainly the relationship with the development of cardiovascular diseases. Moreover, the effects of different lipid-lowering therapies have been described in regard to measurement of microparticles. The studies are still controversial regarding the levels of microparticles that can be considered pathological. In addition, the methodologies used still vary, suggesting the need for standardization of the different protocols applied, aiming at using microparticles as biomarkers in clinical practice

  12. Biomarkers for sepsis: past, present and future

    Directory of Open Access Journals (Sweden)

    Giuseppe Chesi

    2016-12-01

    Full Text Available Sepsis is a complication of severe infection associated with high mortality and open diagnostic issues. Treatment strategies are currently limited and essentially based on prompt recognition, aggressive supportive care and early antibiotic treatment. In the last years, extensive antibiotic use has led to selection, propagation and maintenance of drug-resistant microorganisms. In this context, several biomarkers have been proposed for early identification, etiological definition, risk stratification and improving antibiotic stewardship in septic patient care. Among these molecules, only a few have been translated into clinical practice. In this review, we provided an updated overview of established and developing biomarkers for sepsis, focusing our attention on their pathophysiological profile, advantages, limitations, and appropriate evidence-based use in the management of septic patients.

  13. Biomarkers for Lupus Nephritis: A Critical Appraisal

    Directory of Open Access Journals (Sweden)

    Chi Chiu Mok

    2010-01-01

    Full Text Available Kidney disease is one of the most serious manifestations of systemic lupus erythematosus (SLE. Despite the improvement in the medical care of SLE in the past two decades, the prognosis of lupus nephritis remains unsatisfactory. Besides exploring more effective but less toxic treatment modalities that will further improve the remission rate, early detection and treatment of renal activity may spare patients from intensive immunosuppressive therapies and reduce renal damage. Conventional clinical parameters such as creatinine clearance, proteinuria, urine sediments, anti-dsDNA, and complement levels are not sensitive or specific enough for detecting ongoing disease activity in the lupus kidneys and early relapse of nephritis. Thus, novel biomarkers are necessary to enhance the diagnostic accuracy and sensitivity of lupus renal disease, prognostic stratification, monitoring of treatment response, and detection of early renal flares. This paper reviews promising biomarkers that have recently been evaluated in longitudinal studies of lupus nephritis.

  14. HCC Biomarkers in China and Taiwan

    Directory of Open Access Journals (Sweden)

    Regina M. Santella

    2007-02-01

    Full Text Available

    A number of different types of biomarkers have been used to understand the etiology and progression of hepatocellular cancer (HCC. Perhaps the most well known are the serum/ plasma markers of HBV or HCV infection. These markers include analysis of viral DNA or proteins or antibodies produced against the viral proteins. HBV surface antigen (HBsAg is most frequently used to determine chronic infection with high or low viral replication, while HBeAg is a measure of chronic infection with high viral replication. Analysis of antibodies includes measurement of anti-HBV core antigen, anti-HBV e antigen and anti-HBsAg. The response to immunization can be monitored by analysis of anti-HBsAg. The other major classes of biomarkers used in studies of HCC are biomarkers of exposure to environmental, lifestyle or dietary carcinogens, biomarkers of oxidative stress and early biologic response. In addition, studies of genetic susceptibility have studied polymorphisms in a number of pathways and their role in HCC risk. The biomarkers of exposure include the measurement of carcinogens in urine and carcinogen-DNA and protein adducts. Examples are measurement of aflatoxin and polycyclic aromatic hydrocarbon metabolites, and DNA and protein adducts.

    Biomarkers of oxidative stress include urinary isoprostanes and 8-oxodeoxyguanosine and oxidized plasma proteins. Most of these assays are immunologic although the use of high performance liquid chromatograph (HPLC as well as gas chromatography/mass spectroscopy (GC/MS have been utilized. In nested case-control studies, many of these markers are associated with elevated risk. For example, elevated aflatoxin and polycyclic aromatic hydrocarbon-albumin adducts, aflatoxin metabolites in urine and urinary isoprostanes were observed in baseline samples from

  15. Microparticles as Potential Biomarkers of Cardiovascular Disease

    Energy Technology Data Exchange (ETDEWEB)

    França, Carolina Nunes, E-mail: carolufscar24@gmail.com [Universidade Federal de São Paulo - UNIFESP - UNISA, SP, São Paulo (Brazil); Universidade de Santo Amaro - UNISA, SP, São Paulo (Brazil); Izar, Maria Cristina de Oliveira; Amaral, Jônatas Bussador do; Tegani, Daniela Melo; Fonseca, Francisco Antonio Helfenstein [Universidade Federal de São Paulo - UNIFESP - UNISA, SP, São Paulo (Brazil)

    2015-02-15

    Primary prevention of cardiovascular disease is a choice of great relevance because of its impact on health. Some biomarkers, such as microparticles derived from different cell populations, have been considered useful in the assessment of cardiovascular disease. Microparticles are released by the membrane structures of different cell types upon activation or apoptosis, and are present in the plasma of healthy individuals (in levels considered physiological) and in patients with different pathologies. Many studies have suggested an association between microparticles and different pathological conditions, mainly the relationship with the development of cardiovascular diseases. Moreover, the effects of different lipid-lowering therapies have been described in regard to measurement of microparticles. The studies are still controversial regarding the levels of microparticles that can be considered pathological. In addition, the methodologies used still vary, suggesting the need for standardization of the different protocols applied, aiming at using microparticles as biomarkers in clinical practice.

  16. [Inflammatory biomarkers in ischemic acute coronary syndrome].

    Science.gov (United States)

    Domínguez-Rodríguez, Alberto; Abreu-González, Pedro

    2015-10-01

    Diagnosing acute coronary syndrome (ACS) in the emergency department is often a complex process. Inflammatory markers might be useful for the rapid assessment of a patient's overall risk and might also help predict future episodes. The clinical use of these biomarkers could potentially lower the number of emergency visits and help in the prevention of future adverse events. The aim of this review was to evaluate the clinical utility of markers of cardiovascular inflammation in emergency patients with ACS. Based on a critical analysis of a selection of the literature, we concluded that none of the biomarkers of cardiovascular inflammation would at present be useful for stratifying risk in emergency situations, aiding prognosis, or guiding therapy for patients with ACS.

  17. The human genome project

    International Nuclear Information System (INIS)

    Worton, R.

    1996-01-01

    The Human Genome Project is a massive international research project, costing 3 to 5 billion dollars and expected to take 15 years, which will identify the all the genes in the human genome - i.e. the complete sequence of bases in human DNA. The prize will be the ability to identify genes causing or predisposing to disease, and in some cases the development of gene therapy, but this new knowledge will raise important ethical issues

  18. Decoding the human genome

    CERN Multimedia

    CERN. Geneva. Audiovisual Unit; Antonerakis, S E

    2002-01-01

    Decoding the Human genome is a very up-to-date topic, raising several questions besides purely scientific, in view of the two competing teams (public and private), the ethics of using the results, and the fact that the project went apparently faster and easier than expected. The lecture series will address the following chapters: Scientific basis and challenges. Ethical and social aspects of genomics.

  19. Molluscan Evolutionary Genomics

    Energy Technology Data Exchange (ETDEWEB)

    Simison, W. Brian; Boore, Jeffrey L.

    2005-12-01

    In the last 20 years there have been dramatic advances in techniques of high-throughput DNA sequencing, most recently accelerated by the Human Genome Project, a program that has determined the three billion base pair code on which we are based. Now this tremendous capability is being directed at other genome targets that are being sampled across the broad range of life. This opens up opportunities as never before for evolutionary and organismal biologists to address questions of both processes and patterns of organismal change. We stand at the dawn of a new 'modern synthesis' period, paralleling that of the early 20th century when the fledgling field of genetics first identified the underlying basis for Darwin's theory. We must now unite the efforts of systematists, paleontologists, mathematicians, computer programmers, molecular biologists, developmental biologists, and others in the pursuit of discovering what genomics can teach us about the diversity of life. Genome-level sampling for mollusks to date has mostly been limited to mitochondrial genomes and it is likely that these will continue to provide the best targets for broad phylogenetic sampling in the near future. However, we are just beginning to see an inroad into complete nuclear genome sequencing, with several mollusks and other eutrochozoans having been selected for work about to begin. Here, we provide an overview of the state of molluscan mitochondrial genomics, highlight a few of the discoveries from this research, outline the promise of broadening this dataset, describe upcoming projects to sequence whole mollusk nuclear genomes, and challenge the community to prepare for making the best use of these data.

  20. Human Germline Genome Editing

    OpenAIRE

    Ormond, Kelly E.; Mortlock, Douglas P.; Scholes, Derek T.; Bombard, Yvonne; Brody, Lawrence C.; Faucett, W. Andrew; Garrison, Nanibaa’ A.; Hercher, Laura; Isasi, Rosario; Middleton, Anna; Musunuru, Kiran; Shriner, Daniel; Virani, Alice; Young, Caroline E.

    2017-01-01

    With CRISPR/Cas9 and other genome-editing technologies, successful somatic and germline genome editing are becoming feasible. To respond, an American Society of Human Genetics (ASHG) workgroup developed this position statement, which was approved by the ASHG Board in March 2017. The workgroup included representatives from the UK Association of Genetic Nurses and Counsellors, Canadian Association of Genetic Counsellors, International Genetic Epidemiology Society, and US National Society of Gen...

  1. Novel Bacterial Proteins and Lipids Reveal the Diversity of Triterpenoid Biomarker Synthesis

    Science.gov (United States)

    Wei, J. H.; Banta, A. B.; Gill, C. C. C.; Giner, J. L.; Welander, P. V.

    2017-12-01

    Lipids preserved in sediments and rocks function as organic biomarkers providing evidence for the types of organisms that lived in ancient environments. We use a combined approach utilizing comparative genomics, molecular biology, and lipid analysis to discover novel cyclic triteprenoid lipids and their biosynthetic pathways in bacteria. Here, we present two cases of bacterial synthesis of pentacylic triterpenols previously thought to be indicative of eukaryotes, which address current incongruities in the fossil record. Cyclic triterpenoid lipids, such as hopanoids and sterols, are generally associated with bacteria and eukaryotes, respectively. The pentacyclic triterpenoid tetrahymanol, first discovered in the ciliate Tetrahymena pyriformis, and its diagenetic product gammacerane, have been previously interpreted as markers for eukaryotes and linked to water column stratification. Yet the occurrence of tetrahymanol in bacteria implies our knowledge of extant tetrahymanol producers is not complete. Through comparative genomics we identified a new gene required for tetrahymanol synthesis in the bacterium Methylomicrobium alcaliphilum. This gene encodes a novel enzyme, Tetrahymanol synthase (THS), that synthesizes tetrahymanol from the hopanoid diploptene demonstrating a pathway for tetrahymanol production in bacteria distinct from that in eukaryotes. We bionformatically identified THS homologs in 104 bacterial genomes and 472 metagenomes, implying a great diversity of tetrahymanol producers. Lipids of the arborane class, such as iso-arborinol, are commonly found in modern angiosperms. Arobranes are synthesized by the enzyme oxidosqualene cyclase (OSC), which in plants can form both tetra and pentacyclic molecules. While bacteria are known to produce tetracyclic sterol compounds, bacterial synthesis of pentacyclic arborane class triterpenols of this class were previously undiscovered. We have identified a bacterium, Eudoraea adriatica, whose OSC synthesizes

  2. Identification of Potential Biomarkers for Antimony Susceptibility ...

    Indian Academy of Sciences (India)

    Identification of Potential Biomarkers for Antimony Susceptibility/Resistance in L. donovani Rentala Madhubala School of Life Sciences Jawaharlal Nehru University New Delhi, India · Slide 2 · Slide 3 · Slide 4 · Slide 5 · Slide 6 · Slide 7 · Slide 8 · Slide 9 · Slide 10 · Slide 11 · Slide 12 · Slide 13 · Slide 14 · Slide 15 · Slide 16.

  3. Biomarkers for Wilms Tumor: a Systematic Review

    Science.gov (United States)

    Cone, Eugene B.; Dalton, Stewart S.; Van Noord, Megan; Tracy, Elizabeth T.; Rice, Henry E.; Routh, Jonathan C.

    2016-01-01

    Purpose Wilms tumor is the most common childhood renal malignancy and the fourth most common childhood cancer. Many biomarkers have been studied but there has been no comprehensive summary. We systematically reviewed the literature on biomarkers in Wilms Tumor with the objective of quantifying the prognostic implication of the presence of individual tumor markers. Methods We searched for English language studies from 1980–2015 performed on children with Wilms Tumor under 18 years old with prognostic data. The protocol was conducted as per PRISMA guidelines. Two reviewers abstracted data in duplicate using a standard evaluation form. We performed descriptive statistics, then calculated relative risks and 95% confidence intervals for markers appearing in multiple level 2 or 3 studies. Results 40 studies were included examining 32 biomarkers in 7381 Wilms patients. Studies had a median of 61 patients with 24 biomarker positive patients per study, and a median follow-up of 68.4 months. Median percent of patients in Stage 1, 2, 3, 4, and 5 were 28.5%, 26.4%, 24.5%, 14.1%, and 1.7%, with 10.2% anaplasia. The strongest negative prognostic association was loss of heterozygosity on 11p15, with a risk of recurrence of 5.00, although loss of heterozygosity on 1p and gain of function on 1q were also strongly linked to increased recurrence (2.93 and 2.86 respectively). Conclusions Several tumor markers are associated with an increased risk of recurrence or a decreased risk of overall survival in Wilms Tumor. These data suggest targets for development of diagnostic tests and potential therapies. PMID:27259655

  4. Bayesian methods for proteomic biomarker development

    Directory of Open Access Journals (Sweden)

    Belinda Hernández

    2015-12-01

    In this review we provide an introduction to Bayesian inference and demonstrate some of the advantages of using a Bayesian framework. We summarize how Bayesian methods have been used previously in proteomics and other areas of bioinformatics. Finally, we describe some popular and emerging Bayesian models from the statistical literature and provide a worked tutorial including code snippets to show how these methods may be applied for the evaluation of proteomic biomarkers.

  5. Fibrosis biomarkers in workers exposed to MWCNTs

    International Nuclear Information System (INIS)

    Fatkhutdinova, Liliya M.; Khaliullin, Timur O.; Vasil'yeva, Olga L.; Zalyalov, Ramil R.; Mustafin, Ilshat G.; Kisin, Elena R.; Birch, M. Eileen; Yanamala, Naveena; Shvedova, Anna A.

    2016-01-01

    Multi-walled carbon nanotubes (MWCNT) with their unique physico-chemical properties offer numerous technological advantages and are projected to drive the next generation of manufacturing growth. As MWCNT have already found utility in different industries including construction, engineering, energy production, space exploration and biomedicine, large quantities of MWCNT may reach the environment and inadvertently lead to human exposure. This necessitates the urgent assessment of their potential health effects in humans. The current study was carried out at NanotechCenter Ltd. Enterprise (Tambov, Russia) where large-scale manufacturing of MWCNT along with relatively high occupational exposure levels was reported. The goal of this small cross-sectional study was to evaluate potential biomarkers during occupational exposure to MWCNT. All air samples were collected at the workplaces from both specific areas and personal breathing zones using filter-based devices to quantitate elemental carbon and perform particle analysis by TEM. Biological fluids of nasal lavage, induced sputum and blood serum were obtained from MWCNT-exposed and non-exposed workers for assessment of inflammatory and fibrotic markers. It was found that exposure to MWCNTs caused significant increase in IL-1β, IL6, TNF-α, inflammatory cytokines and KL-6, a serological biomarker for interstitial lung disease in collected sputum samples. Moreover, the level of TGF-β1 was increased in serum obtained from young exposed workers. Overall, the results from this study revealed accumulation of inflammatory and fibrotic biomarkers in biofluids of workers manufacturing MWCNTs. Therefore, the biomarkers analyzed should be considered for the assessment of health effects of occupational exposure to MWCNT in cross-sectional epidemiological studies. - Highlights: • The effects of MWCNT exposure in humans remain unclear. • We found increased KL-6/TGF-β levels in the biofluids of MWCNT-exposed workers.

  6. Biomarkers as Proxies for Life and Environment

    Science.gov (United States)

    Summons, R. E.

    2006-05-01

    Biomarkers are organic molecules that can be used to trace specific types of organisms or biological processes in contemporary ecosystems, ancient sediments and, potentially, beyond the Earth. Biomarkers offer a means to evaluate Earth's biosphere from its earliest development to the modern day. Hydrocarbons, which are the remains of lipids that once resided in the membranes of ancestral organisms, carry chemical and isotopic clues about the nature of early ecosystems. The hydrocarbon remains of fatty acids, sterols, bacterial triterpenoids and pigments are very recalcitrant substances and can be found in rocks as old as 2.8 billion years. These molecules tell us that the three domains, archaea, bacteria and eukarya that comprise all extant life appeared quite early in Earth's history as did the oxygen-producing photosynthesis that oxidized our atmosphere and made it possible for animal life to evolve and increase in complexity. Pigment-derived biomarkers are especially useful for evaluating paleo-environmental conditions. They occur in rocks from the Archean to the present day and can be especially diagnostic for euxinic conditions. The greatest known mass extinction event occurred at the end of the Permian period and extinguished about 70% of the animals and plants that existed at that time. Much controversy surrounds its cause with many different scenarios having been proposed. An international collaboration has enabled biomarker profiles to be obtained from Permian- Triassic boundary sections in China, Australia, Canada, Tibet and Greenland. These data suggest that euxinic conditions prevailed widely in the oceans for an extended period from the Late Permian and that sulfide toxicity may have been a major factor in the demise of both plant and animal life.

  7. Fibrosis biomarkers in workers exposed to MWCNTs

    Energy Technology Data Exchange (ETDEWEB)

    Fatkhutdinova, Liliya M., E-mail: liliya.fatkhutdinova@gmail.com [Kazan State Medical University, ul. Butlerova 49, Kazan 420012 (Russian Federation); Khaliullin, Timur O., E-mail: Khaliullin.40k@gmail.com [Kazan State Medical University, ul. Butlerova 49, Kazan 420012 (Russian Federation); Department of Physiology & Pharmacology, WVU, Morgantown, WV (United States); Vasil' yeva, Olga L., E-mail: volgaleon@gmail.com [Kazan State Medical University, ul. Butlerova 49, Kazan 420012 (Russian Federation); Zalyalov, Ramil R., E-mail: zalyalov.ramil@gmail.com [Kazan State Medical University, ul. Butlerova 49, Kazan 420012 (Russian Federation); Mustafin, Ilshat G., E-mail: ilshat64@mail.ru [Kazan State Medical University, ul. Butlerova 49, Kazan 420012 (Russian Federation); Kisin, Elena R., E-mail: edk8@cdc.gov [National Institute for Occupational Safety and Health, Morgantown, WV (United States); Birch, M. Eileen, E-mail: mib2@cdc.gov [National Institute for Occupational Safety and Health, Cincinnati, OH (United States); Yanamala, Naveena, E-mail: wqu1@cdc.gov [National Institute for Occupational Safety and Health, Morgantown, WV (United States); Shvedova, Anna A., E-mail: ats1@cdc.gov [National Institute for Occupational Safety and Health, Morgantown, WV (United States); Department of Physiology & Pharmacology, WVU, Morgantown, WV (United States)

    2016-05-15

    Multi-walled carbon nanotubes (MWCNT) with their unique physico-chemical properties offer numerous technological advantages and are projected to drive the next generation of manufacturing growth. As MWCNT have already found utility in different industries including construction, engineering, energy production, space exploration and biomedicine, large quantities of MWCNT may reach the environment and inadvertently lead to human exposure. This necessitates the urgent assessment of their potential health effects in humans. The current study was carried out at NanotechCenter Ltd. Enterprise (Tambov, Russia) where large-scale manufacturing of MWCNT along with relatively high occupational exposure levels was reported. The goal of this small cross-sectional study was to evaluate potential biomarkers during occupational exposure to MWCNT. All air samples were collected at the workplaces from both specific areas and personal breathing zones using filter-based devices to quantitate elemental carbon and perform particle analysis by TEM. Biological fluids of nasal lavage, induced sputum and blood serum were obtained from MWCNT-exposed and non-exposed workers for assessment of inflammatory and fibrotic markers. It was found that exposure to MWCNTs caused significant increase in IL-1β, IL6, TNF-α, inflammatory cytokines and KL-6, a serological biomarker for interstitial lung disease in collected sputum samples. Moreover, the level of TGF-β1 was increased in serum obtained from young exposed workers. Overall, the results from this study revealed accumulation of inflammatory and fibrotic biomarkers in biofluids of workers manufacturing MWCNTs. Therefore, the biomarkers analyzed should be considered for the assessment of health effects of occupational exposure to MWCNT in cross-sectional epidemiological studies. - Highlights: • The effects of MWCNT exposure in humans remain unclear. • We found increased KL-6/TGF-β levels in the biofluids of MWCNT-exposed workers.

  8. Measurement of Soluble Biomarkers by Flow Cytometry

    OpenAIRE

    Antal-Szalm?s, P?ter; Nagy, B?la; Debreceni, Ildik? Beke; Kappelmayer, J?nos

    2013-01-01

    Microparticle based flow cytometric assays for determination of the level of soluble biomarkers are widely used in several research applications and in some diagnostic setups. The major advantages of these multiplex systems are that they can measure a large number of analytes (up to 500) at the same time reducing assay time, costs and sample volume. Most of these assays are based on antigen-antibody interactions and work as traditional immunoassays, but nucleic acid alterations ? by using spe...

  9. New serum biomarkers for prostate cancer diagnosis

    Science.gov (United States)

    Chadha, Kailash C.; Miller, Austin; Nair, Bindukumar B.; Schwartz, Stanley A.; Trump, Donald L.; Underwood, Willie

    2014-01-01

    Background Prostate-specific antigen (PSA) is currently used as a biomarker for diagnosis and management of prostate cancer (CaP). However, PSA typically lacks the sensitivity and specificity desired of a diagnostic marker. Objective The goal of this study was to identify an additional biomarker or a panel of biomarkers that is more sensitive and specific than PSA in differentiating benign versus malignant prostate disease and/or localized CaP versus metastatic CaP. Methods Concurrent measurements of circulating interleukin-8 (IL-8), Tumor necrosis factor-α (TNF-α) and soluble tumor necrosis factor-α receptors 1 (sTNFR1) were obtained from four groups of men: (1) Controls (2) with elevated prostate-specific antigen with a negative prostate biopsy (elPSA_negBx) (3) with clinically localized CaP and (4) with castration resistant prostate cancer. Results TNF-α Area under the receiver operating characteristic curve (AUC = 0.93) and sTNFR1 (AUC = 0.97) were strong predictors of elPSA_negBx (vs. CaP). The best predictor of elPSA_negBx vs CaP was sTNFR1 and IL-8 combined (AUC = 0.997). The strongest single predictors of localized versus metastatic CaP were TNF-α (AUC = 0.992) and PSA (AUC = 0.963) levels. Conclusions The specificity and sensitivity of a PSA-based CaP diagnosis can be significantly enhanced by concurrent serum measurements of IL-8, TNF-α and sTNFR1. In view of the concerns about the ability of PSA to distinguish clinically relevant CaP from indolent disease, assessment of these biomarkers in the larger cohort is warranted. PMID:25593898

  10. Recent developments in biomarkers in Parkinson disease

    Science.gov (United States)

    Schapira, Anthony H.V.

    2013-01-01

    Purpose of review Parkinson disease is the second most common neurodegenerative disease after Alzheimer disease, and current demographic trends indicate a life-time risk approaching 4% and predict a doubling of prevalence by 2030. Strategies are being developed to apply recent advances in our understanding of the cause of Parkinson disease to the development of biomarkers that will enable the identification of at-risk individuals, enable early diagnosis and reflect the progression of disease. The latter will be particularly important for the testing of disease-modifying therapies. This review summarizes recent advances in Parkinson disease biomarker development. Recent findings Recent reports continue to reflect the application of a variety of clinical, imaging or biochemical measurements, alone or in combination, to general Parkinson disease populations. Probably the most promising is the assay of alpha-synuclein in the diagnosis and evolution of Parkinson disease. At present, detection techniques are still being refined, but once accurate and reproducible assays are available, it will be important to define the relationship of these to early diagnosis and progression. Alpha-synuclein concentrations may also be modulated by certain disease-modifying agents in development and so may represent a measure of their efficacy. It has to be accepted that no single measure currently fulfils all the necessary criteria for a biomarker in Parkinson disease, but combinations of measures are more likely to deliver benefit. Summary The Parkinson disease biomarker field is approaching a stage when certain combinations of clinical, imaging and biochemical measures may identify a proportion of individuals at risk for developing the disease. However, their general applicability may be limited. Attention is now turning to stratification of Parkinson disease into certain at-risk groups defined by genotype. The application of multimodal screening to these populations may be more

  11. Heritability of Biomarkers of Oxidized Lipoproteins: Twin Pair Study.

    Science.gov (United States)

    Rao, Fangwen; Schork, Andrew J; Maihofer, Adam X; Nievergelt, Caroline M; Marcovina, Santica M; Miller, Elizabeth R; Witztum, Joseph L; O'Connor, Daniel T; Tsimikas, Sotirios

    2015-07-01

    To determine whether biomarkers of oxidized lipoproteins are genetically determined. Lipoprotein(a) (Lp[a]) is a heritable risk factor and carrier of oxidized phospholipids (OxPL). We measured oxidized phospholipids on apolipoprotein B-containing lipoproteins (OxPL-apoB), Lp(a), IgG, and IgM autoantibodies to malondialdehyde-modified low-density lipoprotein, copper oxidized low-density lipoprotein, and apoB-immune complexes in 386 monozygotic and dizygotic twins to estimate trait heritability (h(2)) and determine specific genetic effects among traits. A genome-wide linkage study followed by genetic association was performed. The h(2) (scale: 0-1) for Lp(a) was 0.91±0.01 and for OxPL-apoB 0.87±0.02, which were higher than physiological, inflammatory, or lipid traits. h(2) of IgM malondialdehyde-modified low-density lipoprotein, copper oxidized low-density lipoprotein, and apoB-immune complexes were 0.69±0.04, 0.67±0.05, and 0.80±0.03, respectively, and for IgG malondialdehyde-modified low-density lipoprotein, copper oxidized low-density lipoprotein, and apoB-immune complexes 0.62±0.05, 0.52±0.06, and 0.53±0.06, respectively. There was an inverse correlation between the major apo(a) isoform and OxPL-apoB (R=-0.49; Plipoprotein and copper oxidized low-density lipoprotein, and apoB-immune complexes. Sib-pair genetic linkage of the Lp(a) trait revealed that single nucleotide polymorphism rs10455872 was significantly associated with OxPL-apoB after adjusting for Lp(a). OxPL-apoB and other biomarkers of oxidized lipoproteins are highly heritable cardiovascular risk factors that suggest novel genetic origins of atherothrombosis. © 2015 American Heart Association, Inc.

  12. RadGenomics project

    Energy Technology Data Exchange (ETDEWEB)

    Iwakawa, Mayumi; Imai, Takashi; Harada, Yoshinobu [National Inst. of Radiological Sciences, Chiba (Japan). Frontier Research Center] [and others

    2002-06-01

    Human health is determined by a complex interplay of factors, predominantly between genetic susceptibility, environmental conditions and aging. The ultimate aim of the RadGenomics (Radiation Genomics) project is to understand the implications of heterogeneity in responses to ionizing radiation arising from genetic variation between individuals in the human population. The rapid progression of the human genome sequencing and the recent development of new technologies in molecular genetics are providing us with new opportunities to understand the genetic basis of individual differences in susceptibility to natural and/or artificial environmental factors, including radiation exposure. The RadGenomics project will inevitably lead to improved protocols for personalized radiotherapy and reductions in the potential side effects of such treatment. The project will contribute to future research into the molecular mechanisms of radiation sensitivity in humans and will stimulate the development of new high-throughput technologies for a broader application of biological and medical sciences. The staff members are specialists in a variety of fields, including genome science, radiation biology, medical science, molecular biology, and informatics, and have joined the RadGenomics project from various universities, companies, and research institutes. The project started in April 2001. (author)

  13. Comparative Genome Viewer

    International Nuclear Information System (INIS)

    Molineris, I.; Sales, G.

    2009-01-01

    The amount of information about genomes, both in the form of complete sequences and annotations, has been exponentially increasing in the last few years. As a result there is the need for tools providing a graphical representation of such information that should be comprehensive and intuitive. Visual representation is especially important in the comparative genomics field since it should provide a combined view of data belonging to different genomes. We believe that existing tools are limited in this respect as they focus on a single genome at a time (conservation histograms) or compress alignment representation to a single dimension. We have therefore developed a web-based tool called Comparative Genome Viewer (Cgv): it integrates a bidimensional representation of alignments between two regions, both at small and big scales, with the richness of annotations present in other genome browsers. We give access to our system through a web-based interface that provides the user with an interactive representation that can be updated in real time using the mouse to move from region to region and to zoom in on interesting details.

  14. Human social genomics.

    Directory of Open Access Journals (Sweden)

    Steven W Cole

    2014-08-01

    Full Text Available A growing literature in human social genomics has begun to analyze how everyday life circumstances influence human gene expression. Social-environmental conditions such as urbanity, low socioeconomic status, social isolation, social threat, and low or unstable social status have been found to associate with differential expression of hundreds of gene transcripts in leukocytes and diseased tissues such as metastatic cancers. In leukocytes, diverse types of social adversity evoke a common conserved transcriptional response to adversity (CTRA characterized by increased expression of proinflammatory genes and decreased expression of genes involved in innate antiviral responses and antibody synthesis. Mechanistic analyses have mapped the neural "social signal transduction" pathways that stimulate CTRA gene expression in response to social threat and may contribute to social gradients in health. Research has also begun to analyze the functional genomics of optimal health and thriving. Two emerging opportunities now stand to revolutionize our understanding of the everyday life of the human genome: network genomics analyses examining how systems-level capabilities emerge from groups of individual socially sensitive genomes and near-real-time transcriptional biofeedback to empirically optimize individual well-being in the context of the unique genetic, geographic, historical, developmental, and social contexts that jointly shape the transcriptional realization of our innate human genomic potential for thriving.

  15. RadGenomics project

    International Nuclear Information System (INIS)

    Iwakawa, Mayumi; Imai, Takashi; Harada, Yoshinobu

    2002-01-01

    Human health is determined by a complex interplay of factors, predominantly between genetic susceptibility, environmental conditions and aging. The ultimate aim of the RadGenomics (Radiation Genomics) project is to understand the implications of heterogeneity in responses to ionizing radiation arising from genetic variation between individuals in the human population. The rapid progression of the human genome sequencing and the recent development of new technologies in molecular genetics are providing us with new opportunities to understand the genetic basis of individual differences in susceptibility to natural and/or artificial environmental factors, including radiation exposure. The RadGenomics project will inevitably lead to improved protocols for personalized radiotherapy and reductions in the potential side effects of such treatment. The project will contribute to future research into the molecular mechanisms of radiation sensitivity in humans and will stimulate the development of new high-throughput technologies for a broader application of biological and medical sciences. The staff members are specialists in a variety of fields, including genome science, radiation biology, medical science, molecular biology, and informatics, and have joined the RadGenomics project from various universities, companies, and research institutes. The project started in April 2001. (author)

  16. Salivary pH: A diagnostic biomarker

    Directory of Open Access Journals (Sweden)

    Sharmila Baliga

    2013-01-01

    Full Text Available Objectives: Saliva contains a variety of host defense factors. It influences calculus formation and periodontal disease. Different studies have been done to find exact correlation of salivary biomarkers with periodontal disease. With a multitude of biomarkers and complexities in their determination, the salivary pH may be tried to be used as a quick chairside test. The aim of this study was to analyze the pH of saliva and determine its relevance to the severity of periodontal disease. Study Design: The study population consisted of 300 patients. They were divided into three groups of 100 patients each: Group A had clinically healthy gingiva, Group B who had generalized chronic gingivitis and Group C who had generalized chronic periodontitis. The randomized unstimulated saliva from each patient was collected and pH was tested. Data was analyzed statistically using analysis of variance technique. Results: The salivary pH was more alkaline for patients with generalized chronic gingivitis as compared with the control group (P = 0.001 whereas patients with generalized chronic periodontitis had more acidic pH as compared with the control group (P = 0.001. Conclusion: These results indicate a significant change in the pH depending on the severity of the periodontal condition. The salivary pH shows significant changes and thus relevance to the severity of periodontal disease. Salivary pH may thus be used as a quick chairside diagnostic biomarker.

  17. Salivary pH: A diagnostic biomarker.

    Science.gov (United States)

    Baliga, Sharmila; Muglikar, Sangeeta; Kale, Rahul

    2013-07-01

    Saliva contains a variety of host defense factors. It influences calculus formation and periodontal disease. Different studies have been done to find exact correlation of salivary biomarkers with periodontal disease. With a multitude of biomarkers and complexities in their determination, the salivary pH may be tried to be used as a quick chairside test. The aim of this study was to analyze the pH of saliva and determine its relevance to the severity of periodontal disease. The study population consisted of 300 patients. They were divided into three groups of 100 patients each: Group A had clinically healthy gingiva, Group B who had generalized chronic gingivitis and Group C who had generalized chronic periodontitis. The randomized unstimulated saliva from each patient was collected and pH was tested. Data was analyzed statistically using analysis of variance technique. The salivary pH was more alkaline for patients with generalized chronic gingivitis as compared with the control group (P = 0.001) whereas patients with generalized chronic periodontitis had more acidic pH as compared with the control group (P = 0.001). These results indicate a significant change in the pH depending on the severity of the periodontal condition. The salivary pH shows significant changes and thus relevance to the severity of periodontal disease. Salivary pH may thus be used as a quick chairside diagnostic biomarker.

  18. Plasma biomarker of dietary phytosterol intake.

    Science.gov (United States)

    Lin, Xiaobo; Racette, Susan B; Ma, Lina; Wallendorf, Michael; Spearie, Catherine Anderson; Ostlund, Richard E

    2015-01-01

    Dietary phytosterols, plant sterols structurally similar to cholesterol, reduce intestinal cholesterol absorption and have many other potentially beneficial biological effects in humans. Due to limited information on phytosterol levels in foods, however, it is difficult to quantify habitual dietary phytosterol intake (DPI). Therefore, we sought to identify a plasma biomarker of DPI. Data were analyzed from two feeding studies with a total of 38 subjects during 94 dietary periods. DPI was carefully controlled at low, intermediate, and high levels. Plasma levels of phytosterols and cholesterol metabolites were assessed at the end of each diet period. Based on simple ordinary least squares regression analysis, the best biomarker for DPI was the ratio of plasma campesterol to the endogenous cholesterol metabolite 5-α-cholestanol (R2 = 0.785, P 0.600; P phytosterol intake. Conversely, plasma phytosterol levels alone are not ideal biomarkers of DPI because they are confounded by large inter-individual variation in absorption and turnover of non-cholesterol sterols. Further work is needed to assess the relation between non-cholesterol sterol metabolism and associated cholesterol transport in the genesis of coronary heart disease.

  19. Biomarkers and correlative endpoints for immunotherapy trials.

    Science.gov (United States)

    Morse, Michael A; Osada, Takuya; Hobeika, Amy; Patel, Sandip; Lyerly, H Kim

    2013-01-01

    Immunotherapies for lung cancer are reaching phase III clinical trial, but the ultimate success likely will depend on developing biomarkers to guide development and choosing patient populations most likely to benefit. Because the immune response to cancer involves multiple cell types and cytokines, some spatially and temporally separated, it is likely that multiple biomarkers will be required to fully characterize efficacy of the vaccine and predict eventual benefit. Peripheral blood markers of response, such as the ELISPOT assay and cytokine flow cytometry analyses of peripheral blood mononuclear cells following immunotherapy, remain the standard approach, but it is increasingly important to obtain tissue to study the immune response at the site of the tumor. Earlier clinical endpoints such as response rate and progression-free survival do not correlate with overall survival demonstrated for some immunotherapies, suggesting the need to develop other intermediary clinical endpoints. Insofar as all these biomarkers and surrogate endpoints are relevant in multiple malignancies, it may be possible to extrapolate findings to immunotherapy of lung cancer.

  20. Biomarkers for cardiac cachexia: reality or utopia.

    Science.gov (United States)

    Martins, Telma; Vitorino, Rui; Amado, Francisco; Duarte, José Alberto; Ferreira, Rita

    2014-09-25

    Cardiac cachexia is a serious complication of chronic heart failure, characterized by significant weight loss and body wasting. Chronic heart failure-related muscle wasting results from a chronic imbalance in the activation of anabolic or catabolic pathways, caused by a series of immunological, metabolic, and neurohormonal processes. In spite of the high morbidity and mortality associated to this condition, there is no universally accepted definition or specific biomarkers for cardiac cachexia, which makes its diagnosis and treatment difficult. Several hormonal, inflammatory and oxidative stress molecules have been proposed as serological markers of prognosis in cardiac cachexia but with doubtful success. As individual biomarkers may have limited sensitivity and specificity, multimarker strategies involving mediators of the biological processes modulated by cardiac cachexia will strongly contribute for the diagnosis and management of the disease, as well as for the establishment of new therapeutic targets. An integrated analysis of the biomarkers proposed so far for cardiac cachexia is made in the present review, highlighting the biological processes to which they are related. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Urine Exosomes: An Emerging Trove of Biomarkers.

    Science.gov (United States)

    Street, J M; Koritzinsky, E H; Glispie, D M; Star, R A; Yuen, P S T

    Exosomes are released by most cells and can be isolated from all biofluids including urine. Exosomes are small vesicles formed as part of the endosomal pathway that contain cellular material surrounded by a lipid bilayer that can be traced to the plasma membrane. Exosomes are potentially a more targeted source of material for biomarker discovery than unfractionated urine, and provide diagnostic and pathophysiological information without an invasive tissue biopsy. Cytoplasmic contents including protein, mRNA, miRNA, and lipids have all been studied within the exosomal fraction. Many prospective urinary exosomal biomarkers have been successfully identified for a variety of kidney or genitourinary tract conditions; detection of systemic conditions may also be possible. Isolation and analysis of exosomes can be achieved by several approaches, although many require specialized equipment or involve lengthy protocols. The need for timely analysis in the clinical setting has driven considerable innovation with several promising options recently emerging. Consensus on exosome isolation, characterization, and normalization procedures would resolve critical clinical translational bottlenecks for existing candidate exosomal biomarkers and provide a template for additional discovery studies. 2017 Published by Elsevier Inc.

  2. Aberrant expression of PlncRNA-1 and TUG1: potential biomarkers for gastric cancer diagnosis and clinically monitoring cancer progression.

    Science.gov (United States)

    Baratieh, Zohreh; Khalaj, Zahra; Honardoost, Mohammad Amin; Emadi-Baygi, Modjtaba; Khanahmad, Hossein; Salehi, Mansoor; Nikpour, Parvaneh

    2017-12-01

    To evaluate PlncRNA-1, TUG1 and FAM83H-AS1 gene expression and their possible role as a biomarker in gastric cancer (GC) progression. Long noncoding RNA expressions and clinicopathological characteristics were assessed in 70 paired GC tissues. Furthermore, corresponding data from 318 GC patients were downloaded from The Cancer Genome Atlas database. Expression of PlncRNA-1 and TUG1 were significantly upregulated in GC tumoral tissues, and significantly correlated with clinicopathological characters. However, FAM83H-AS1 showed no consistently differential expression. The expression of these three long noncoding RNAs was significantly higher in The Cancer Genome Atlas tumoral tissues. In conclusion, PlncRNA-1 and TUG1 genes may play a critical role in GC progression and may serve as potential diagnostic biomarkers in GC patients.

  3. Towards understanding and predicting suicidality in women: biomarkers and clinical risk assessment.

    Science.gov (United States)

    Levey, D F; Niculescu, E M; Le-Niculescu, H; Dainton, H L; Phalen, P L; Ladd, T B; Weber, H; Belanger, E; Graham, D L; Khan, F N; Vanipenta, N P; Stage, E C; Ballew, A; Yard, M; Gelbart, T; Shekhar, A; Schork, N J; Kurian, S M; Sandusky, G E; Salomon, D R; Niculescu, A B

    2016-06-01

    Women are under-represented in research on suicidality to date. Although women have a lower rate of suicide completion than men, due in part to the less-violent methods used, they have a higher rate of suicide attempts. Our group has previously identified genomic (blood gene expression biomarkers) and clinical information (apps) predictors for suicidality in men. We now describe pilot studies in women. We used a powerful within-participant discovery approach to identify genes that change in expression between no suicidal ideation (no SI) and high suicidal ideation (high SI) states (n=12 participants out of a cohort of 51 women psychiatric participants followed longitudinally, with diagnoses of bipolar disorder, depression, schizoaffective disorder and schizophrenia). We then used a Convergent Functional Genomics (CFG) approach to prioritize the candidate biomarkers identified in the discovery step by using all the prior evidence in the field. Next, we validated for suicidal behavior the top-ranked biomarkers for SI, in a demographically matched cohort of women suicide completers from the coroner's office (n=6), by assessing which markers were stepwise changed from no SI to high SI to suicide completers. We then tested the 50 biomarkers that survived Bonferroni correction in the validation step, as well as top increased and decreased biomarkers from the discovery and prioritization steps, in a completely independent test cohort of women psychiatric disorder participants for prediction of SI (n=33) and in a future follow-up cohort of psychiatric disorder participants for prediction of psychiatric hospitalizations due to suicidality (n=24). Additionally, we examined how two clinical instruments in the form of apps, Convergent Functional Information for Suicidality (CFI-S) and Simplified Affective State Scale (SASS), previously tested in men, perform in women. The top CFI-S item distinguishing high SI from no SI states was the chronic stress of social isolation. We

  4. Ultrafast comparison of personal genomes

    OpenAIRE

    Mauldin, Denise; Hood, Leroy; Robinson, Max; Glusman, Gustavo

    2017-01-01

    We present an ultra-fast method for comparing personal genomes. We transform the standard genome representation (lists of variants relative to a reference) into 'genome fingerprints' that can be readily compared across sequencing technologies and reference versions. Because of their reduced size, computation on the genome fingerprints is fast and requires little memory. This enables scaling up a variety of important genome analyses, including quantifying relatedness, recognizing duplicative s...

  5. Human genome meeting 2016

    OpenAIRE

    Srivastava, A. K.; Wang, Y.; Huang, R.; Skinner, C.; Thompson, T.; Pollard, L.; Wood, T.; Luo, F.; Stevenson, R.; Polimanti, R.; Gelernter, J.; Lin, X.; Lim, I. Y.; Wu, Y.; Teh, A. L.

    2016-01-01

    Table of contents O1 The metabolomics approach to autism: identification of biomarkers for early detection of autism spectrum disorder A. K. Srivastava, Y. Wang, R. Huang, C. Skinner, T. Thompson, L. Pollard, T. Wood, F. Luo, R. Stevenson O2 Phenome-wide association study for smoking- and drinking-associated genes in 26,394 American women with African, Asian, European, and Hispanic descents R. Polimanti, J. Gelernter O3 Effects of prenatal environment, genotype and DNA methylation on birth we...

  6. Use of biomarkers in ALS drug development and clinical trials.

    Science.gov (United States)

    Bakkar, Nadine; Boehringer, Ashley; Bowser, Robert

    2015-05-14

    The past decade has seen a dramatic increase in the discovery of candidate biomarkers for ALS. These biomarkers typically can either differentiate ALS from control subjects or predict disease course (slow versus fast progression). At the same time, late-stage clinical trials for ALS have failed to generate improved drug treatments for ALS patients. Incorporation of biomarkers into the ALS drug development pipeline and the use of biologic and/or imaging biomarkers in early- and late-stage ALS clinical trials have been absent and only recently pursued in early-phase clinical trials. Further clinical research studies are needed to validate biomarkers for disease progression and develop biomarkers that can help determine that a drug has reached its target within the central nervous system. In this review we summarize recent progress in biomarkers across ALS model systems and patient population, and highlight continued research directions for biomarkers that stratify the patient population to enrich for patients that may best respond to a drug candidate, monitor disease progression and track drug responses in clinical trials. It is crucial that we further develop and validate ALS biomarkers and incorporate these biomarkers into the ALS drug development process. This article is part of a Special Issue entitled ALS complex pathogenesis. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. The current status of biomarkers for predicting toxicity

    Science.gov (United States)

    Campion, Sarah; Aubrecht, Jiri; Boekelheide, Kim; Brewster, David W; Vaidya, Vishal S; Anderson, Linnea; Burt, Deborah; Dere, Edward; Hwang, Kathleen; Pacheco, Sara; Saikumar, Janani; Schomaker, Shelli; Sigman, Mark; Goodsaid, Federico

    2013-01-01

    Introduction There are significant rates of attrition in drug development. A number of compounds fail to progress past preclinical development due to limited tools that accurately monitor toxicity in preclinical studies and in the clinic. Research has focused on improving tools for the detection of organ-specific toxicity through the identification and characterization of biomarkers of toxicity. Areas covered This article reviews what we know about emerging biomarkers in toxicology, with a focus on the 2012 Northeast Society of Toxicology meeting titled ‘Translational Biomarkers in Toxicology.’ The areas covered in this meeting are summarized and include biomarkers of testicular injury and dysfunction, emerging biomarkers of kidney injury and translation of emerging biomarkers from preclinical species to human populations. The authors also provide a discussion about the biomarker qualification process and possible improvements to this process. Expert opinion There is currently a gap between the scientific work in the development and qualification of novel biomarkers for nonclinical drug safety assessment and how these biomarkers are actually used in drug safety assessment. A clear and efficient path to regulatory acceptance is needed so that breakthroughs in the biomarker toolkit for nonclinical drug safety assessment can be utilized to aid in the drug development process. PMID:23961847

  8. Evaluating biomarkers for prognostic enrichment of clinical trials.

    Science.gov (United States)

    Kerr, Kathleen F; Roth, Jeremy; Zhu, Kehao; Thiessen-Philbrook, Heather; Meisner, Allison; Wilson, Francis Perry; Coca, Steven; Parikh, Chirag R

    2017-12-01

    A potential use of biomarkers is to assist in prognostic enrichment of clinical trials, where only patients at relatively higher risk for an outcome of interest are eligible for the trial. We investigated methods for evaluating biomarkers for prognostic enrichment. We identified five key considerations when considering a biomarker and a screening threshold for prognostic enrichment: (1) clinical trial sample size, (2) calendar time to enroll the trial, (3) total patient screening costs and the total per-patient trial costs, (4) generalizability of trial results, and (5) ethical evaluation of trial eligibility criteria. Items (1)-(3) are amenable to quantitative analysis. We developed the Biomarker Prognostic Enrichment Tool for evaluating biomarkers for prognostic enrichment at varying levels of screening stringency. We demonstrate that both modestly prognostic and strongly prognostic biomarkers can improve trial metrics using Biomarker Prognostic Enrichment Tool. Biomarker Prognostic Enrichment Tool is available as a webtool at http://prognosticenrichment.com and as a package for the R statistical computing platform. In some clinical settings, even biomarkers with modest prognostic performance can be useful for prognostic enrichment. In addition to the quantitative analysis provided by Biomarker Prognostic Enrichment Tool, investigators must consider the generalizability of trial results and evaluate the ethics of trial eligibility criteria.

  9. Biomarker Production and Preservation on Europa

    Science.gov (United States)

    Buffo, J.; Schmidt, B. E.

    2017-12-01

    Future landing site selection and sampling techniques for Europa will concentrate on locations of high potential biomarker preservation, however it is unclear what the best targets might be. On Europa, the scenario is quite unlike the depositional surface environments of terrestrial planets we've studied thus far-Europa's surface is passively communicating with putative habitable niches below that extend throughout the ice shell, ocean and sea floor. In this work, I approach biomarker production and preservation on Europa based by considering the many hypotheses that govern the its habitability, the processes that occur within the sea floor, ocean, and ice and exchange between them, and the geologic hypotheses for the formation of its various surfaces to establish, what journey through the planet a biomarker might take to arrive, if possible, at the surface where it is accessible to near-term landed missions. The goal of this project is to construct a simple model through which to consider the context for sampled material that will provide us with the ability to identify limitations in our intuition, understanding of the Europan system, our current hypotheses and data, and provide a road map for developing both areas for new research and identifying technology gaps that we must overcome before we can confidently select a landing site or analyze a sample from the near surface of Europa. I first consider the nature of the environment, i.e. at the sea floor interface, the ocean, or ocean-ice interface, in order to establish what the likely "biomarker" could be and then trace its path through the system: downwelling through the shell, mixing through the ocean, and pathways to the surface. Importantly, many models exist for the production of Europa's surface and subsurface geology that could affect the integrity of a putative biomarker. Often we modulate such considerations as a function of the time-scales over which the geologic process occurs, however such processes

  10. Integration and comparison of different genomic data for outcome prediction in cancer

    OpenAIRE

    Gomez Rueda, Hugo; Martínez Ledesma, Emmanuel; Martínez Torteya, Antonio; Palacios Corona, Rebeca; Treviño, Victor

    2005-01-01

    Background In cancer, large-scale technologies such as next-generation sequencing and microarrays have produced a wide number of genomic features such as DNA copy number alterations (CNA), mRNA expression (EXPR), microRNA expression (MIRNA), and DNA somatic mutations (MUT), among others. Several analyses of a specific type of these genomic data have generated many prognostic biomarkers in cancer. However, it is uncertain which of these data is more powerful and whether the best data-type is c...

  11. Genomics using the Assembly of the Mink Genome

    DEFF Research Database (Denmark)

    Guldbrandtsen, Bernt; Cai, Zexi; Sahana, Goutam

    2018-01-01

    The American Mink’s (Neovison vison) genome has recently been sequenced. This opens numerous avenues of research both for studying the basic genetics and physiology of the mink as well as genetic improvement in mink. Using genotyping-by-sequencing (GBS) generated marker data for 2,352 Danish farm...... mink runs of homozygosity (ROH) were detect in mink genomes. Detectable ROH made up on average 1.7% of the genome indicating the presence of at most a moderate level of genomic inbreeding. The fraction of genome regions found in ROH varied. Ten percent of the included regions were never found in ROH....... The ability to detect ROH in the mink genome also demonstrates the general reliability of the new mink genome assembly. Keywords: american mink, run of homozygosity, genome, selection, genomic inbreeding...

  12. Cocktail effects on biomarker responses in fish

    Energy Technology Data Exchange (ETDEWEB)

    Celander, Malin C., E-mail: malin.celander@zool.gu.se [University of Gothenburg, Department of Zoology, Box 463, SE-405 30 Gothenburg (Sweden)

    2011-10-15

    One of today's greatest challenges in environmental toxicology is to understand effects of mixture toxicity, commonly referred to as cocktail effects, in humans and in wildlife. Biomarker responses in fish are routinely used to assess exposure of anthropogenic chemicals in the aquatic environment. However, little is known about how cocktail effects affect these biomarker responses. For this reason, there is an obvious risk for misinterpretation of biomarker-data and this can have profound negative effects on stakeholder's decisions and actions, as well as on legislations and remediation-plans initiated in order to reduce exposure to certain chemicals. Besides, chemical safety-levels are traditionally based on experiences from lab-studies with single chemicals, which is unfortunate as a chemical can be more toxic when it is mixed with other chemicals, because of the cocktail effect. This review focuses on pharmacokinetic interactions between different classes of pollutants on detoxification mechanisms and how that affects two commonly used biomarkers in the aquatic environment: (1) induction of cytochrome P450 1A (CYP1A) that is mediated via activation of the arylhydrocarbon receptor (AhR), used to assess exposure to aromatic hydrocarbons; (2) induction of vitellogenin (VTG) that is mediated via activation of the estrogen receptor (ER), used to assess exposure to estrogenic chemicals. These responses can be either directly or indirectly affected by the presence of other classes of pollutants as a result of cocktail effects. For example, chemicals that inhibit the function of key metabolic enzymes and transporter pumps that are involved in elimination of AhR- and ER agonists, can result in bioaccumulation of aromatic hydrocarbons and estrogenic chemicals resulting in increased biomarker responses. This cocktail effect can lead to overestimation of the actual exposure pressure. On the contrary, induction of expression of key metabolic enzymes and transporter

  13. Genome size analyses of Pucciniales reveal the largest fungal genomes.

    Science.gov (United States)

    Tavares, Sílvia; Ramos, Ana Paula; Pires, Ana Sofia; Azinheira, Helena G; Caldeirinha, Patrícia; Link, Tobias; Abranches, Rita; Silva, Maria do Céu; Voegele, Ralf T; Loureiro, João; Talhinhas, Pedro

    2014-01-01

    Rust fungi (Basidiomycota, Pucciniales) are biotrophic plant pathogens which exhibit diverse complexities in their life cycles and host ranges. The completion of genome sequencing of a few rust fungi has revealed the occurrence of large genomes. Sequencing efforts for other rust fungi have been hampered by uncertainty concerning their genome sizes. Flow cytometry was recently applied to estimate the genome size of a few rust fungi, and confirmed the occurrence of large genomes in this order (averaging 225.3 Mbp, while the average for Basidiomycota was 49.9 Mbp and was 37.7 Mbp for all fungi). In this work, we have used an innovative and simple approach to simultaneously isolate nuclei from the rust and its host plant in order to estimate the genome size of 30 rust species by flow cytometry. Genome sizes varied over 10-fold, from 70 to 893 Mbp, with an average genome size value of 380.2 Mbp. Compared to the genome sizes of over 1800 fungi, Gymnosporangium confusum possesses the largest fungal genome ever reported (893.2 Mbp). Moreover, even the smallest rust genome determined in this study is larger than the vast majority of fungal genomes (94%). The average genome size of the Pucciniales is now of 305.5 Mbp, while the average Basidiomycota genome size has shifted to 70.4 Mbp and the average for all fungi reached 44.2 Mbp. Despite the fact that no correlation could be drawn between the genome sizes, the phylogenomics or the life cycle of rust fungi, it is interesting to note that rusts with Fabaceae hosts present genomes clearly larger than those with Poaceae hosts. Although this study comprises only a small fraction of the more than 7000 rust species described, it seems already evident that the Pucciniales represent a group where genome size expansion could be a common characteristic. This is in sharp contrast to sister taxa, placing this order in a relevant position in fungal genomics research.

  14. Break Breast Cancer Addiction by CRISPR/Cas9 Genome Editing

    OpenAIRE

    Yang, Haitao; Jaeger, MariaLynn; Walker, Averi; Wei, Daniel; Leiker, Katie; Weitao, Tao

    2018-01-01

    Breast cancer is the leading diagnosed cancer for women globally. Evolution of breast cancer in tumorigenesis, metastasis and treatment resistance appears to be driven by the aberrant gene expression and protein degradation encoded by the cancer genomes. The uncontrolled cancer growth relies on these cellular events, thus constituting the cancerous programs and rendering the addiction towards them. These programs are likely the potential anticancer biomarkers for Personalized Medicine of brea...

  15. A GMM-IG framework for selecting genes as expression panel biomarkers.

    Science.gov (United States)

    Wang, Mingyi; Chen, Jake Y

    2010-01-01

    The limitation of small sample size of functional genomics experiments has made it necessary to integrate DNA microarray experimental data from different sources. However, experimentation noises and biases of different microarray platforms have made integrated data analysis challenging. In this work, we propose an integrative computational framework to identify candidate biomarker genes from publicly available functional genomics studies. We developed a new framework, Gaussian Mixture Modeling-Coupled Information Gain (GMM-IG). In this framework, we first apply a two-component Gaussian mixture model (GMM) to estimate the conditional probability distributions of gene expression data between two different types of samples, for example, normal versus cancer. An expectation-maximization algorithm is then used to estimate the maximum likelihood parameters of a mixture of two Gaussian models in the feature space and determine the underlying expression levels of genes. Gene expression results from different studies are discretized, based on GMM estimations and then unified. Significantly differentially-expressed genes are filtered and assessed with information gain (IG) measures. DNA microarray experimental data for lung cancers from three different prior studies was processed using the new GMM-IG method. Target gene markers from a gene expression panel were selected and compared with several conventional computational biomarker data analysis methods. GMM-IG showed consistently high accuracy for several classification assessments. A high reproducibility of gene selection results was also determined from statistical validations. Our study shows that the GMM-IG framework can overcome poor reliability issues from single-study DNA microarray experiment while maintaining high accuracies by combining true signals from multiple studies. We present a conceptually simple framework that enables reliable integration of true differential gene expression signals from multiple

  16. Biomarkers in spinal cord compression Ethics and perspectives

    Directory of Open Access Journals (Sweden)

    Iencean A.St.

    2016-09-01

    Full Text Available The phosphorylated form of the high-molecular-weight neurofilament subunit NF-H (pNF-H in serum or in cerebro-spinal fluid (CSF is a specific lesional biomarker for spinal cord injury. The lesional biomarkers and the reaction biomarkers are both presented after several hours post-injury. The specific predictive patterns of lesional biomarkers could be used to aid clinicians with making a diagnosis and establishing a prognosis, and evaluating therapeutic interventions. Diagnosis, prognosis, and treatment guidance based on biomarker used as a predictive indicator can determine ethical difficulties by differentiated therapies in patients with spinal cord compression. At this point based on studies until today we cannot take a decision based on biomarker limiting the treatment of neurological recovery in patients with complete spinal cord injury because we do not know the complexity of the biological response to spinal cord compression.

  17. Biomarkers of Aging: From Function to Molecular Biology

    Directory of Open Access Journals (Sweden)

    Karl-Heinz Wagner

    2016-06-01

    Full Text Available Aging is a major risk factor for most chronic diseases and functional impairments. Within a homogeneous age sample there is a considerable variation in the extent of disease and functional impairment risk, revealing a need for valid biomarkers to aid in characterizing the complex aging processes. The identification of biomarkers is further complicated by the diversity of biological living situations, lifestyle activities and medical treatments. Thus, there has been no identification of a single biomarker or gold standard tool that can monitor successful or healthy aging. Within this short review the current knowledge of putative biomarkers is presented, focusing on their application to the major physiological mechanisms affected by the aging process including physical capability, nutritional status, body composition, endocrine and immune function. This review emphasizes molecular and DNA-based biomarkers, as well as recent advances in other biomarkers such as microRNAs, bilirubin or advanced glycation end products.

  18. The Wide and Complex Field of NAFLD Biomarker Research: Trends.

    Science.gov (United States)

    Wichro, Erika; Macheiner, Tanja; Schmid, Jasmin; Kavsek, Barbara; Sargsyan, Karine

    2014-01-01

    Background. Nonalcoholic fatty liver disease is now acknowledged as a complex public health issue linked to sedentary lifestyle, obesity, and related disorders like type 2 diabetes and metabolic syndrome. Aims. We aimed to retrieve its trends out of the huge amount of published data. Therefore, we conducted an extensive literature search to identify possible biomarker and/or biomarker combinations by retrospectively assessing and evaluating common and novel biomarkers to predict progression and prognosis of obesity related liver diseases. Methodology. We analyzed finally 62 articles accounting for 157 cohorts and 45,288 subjects. Results. Despite the various approaches, most cohorts were considerably small and rarely comparable. Also, we found that the same standard parameters were measured rather than novel biomarkers. Diagnostics approaches appeared incomparable. Conclusions. Further collaborative investigations on harmonizing ways of data acquisition and identifying such biomarkers for clinical use are necessary to yield sufficient significant results of potential biomarkers.

  19. Genomes to Proteomes

    Energy Technology Data Exchange (ETDEWEB)

    Panisko, Ellen A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Grigoriev, Igor [USDOE Joint Genome Inst., Walnut Creek, CA (United States); Daly, Don S. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Webb-Robertson, Bobbie-Jo [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Baker, Scott E. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2009-03-01

    Biologists are awash with genomic sequence data. In large part, this is due to the rapid acceleration in the generation of DNA sequence that occurred as public and private research institutes raced to sequence the human genome. In parallel with the large human genome effort, mostly smaller genomes of other important model organisms were sequenced. Projects following on these initial efforts have made use of technological advances and the DNA sequencing infrastructure that was built for the human and other organism genome projects. As a result, the genome sequences of many organisms are available in high quality draft form. While in many ways this is good news, there are limitations to the biological insights that can be gleaned from DNA sequences alone; genome sequences offer only a bird's eye view of the biological processes endemic to an organism or community. Fortunately, the genome sequences now being produced at such a high rate can serve as the foundation for other global experimental platforms such as proteomics. Proteomic methods offer a snapshot of the proteins present at a point in time for a given biological sample. Current global proteomics methods combine enzymatic digestion, separations, mass spectrometry and database searching for peptide identification. One key aspect of proteomics is the prediction of peptide sequences from mass spectrometry data. Global proteomic analysis uses computational matching of experimental mass spectra with predicted spectra based on databases of gene models that are often generated computationally. Thus, the quality of gene models predicted from a genome sequence is crucial in the generation of high quality peptide identifications. Once peptides are identified they can be assigned to their parent protein. Proteins identified as expressed in a given experiment are most useful when compared to other expressed proteins in a larger biological context or biochemical pathway. In this chapter we will discuss the automatic

  20. Experimental Induction of Genome Chaos.

    Science.gov (United States)

    Ye, Christine J; Liu, Guo; Heng, Henry H

    2018-01-01

    Genome chaos, or karyotype chaos, represents a powerful survival strategy for somatic cells under high levels of stress/selection. Since the genome context, not the gene content, encodes the genomic blueprint of the cell, stress-induced rapid and massive reorganization of genome topology functions as a very important mechanism for genome (karyotype) evolution. In recent years, the phenomenon of genome chaos has been confirmed by various sequencing efforts, and many different terms have been coined to describe different subtypes of the chaotic genome including "chromothripsis," "chromoplexy," and "structural mutations." To advance this exciting field, we need an effective experimental system to induce and characterize the karyotype reorganization process. In this chapter, an experimental protocol to induce chaotic genomes is described, following a brief discussion of the mechanism and implication of genome chaos in cancer evolution.

  1. Genome Sequences of Oryza Species

    KAUST Repository

    Kumagai, Masahiko; Tanaka, Tsuyoshi; Ohyanagi, Hajime; Hsing, Yue-Ie C.; Itoh, Takeshi

    2018-01-01

    This chapter summarizes recent data obtained from genome sequencing, annotation projects, and studies on the genome diversity of Oryza sativa and related Oryza species. O. sativa, commonly known as Asian rice, is the first monocot species whose complete genome sequence was deciphered based on physical mapping by an international collaborative effort. This genome, along with its accurate and comprehensive annotation, has become an indispensable foundation for crop genomics and breeding. With the development of innovative sequencing technologies, genomic studies of O. sativa have dramatically increased; in particular, a large number of cultivars and wild accessions have been sequenced and compared with the reference rice genome. Since de novo genome sequencing has become cost-effective, the genome of African cultivated rice, O. glaberrima, has also been determined. Comparative genomic studies have highlighted the independent domestication processes of different rice species, but it also turned out that Asian and African rice share a common gene set that has experienced similar artificial selection. An international project aimed at constructing reference genomes and examining the genome diversity of wild Oryza species is currently underway, and the genomes of some species are publicly available. This project provides a platform for investigations such as the evolution, development, polyploidization, and improvement of crops. Studies on the genomic diversity of Oryza species, including wild species, should provide new insights to solve the problem of growing food demands in the face of rapid climatic changes.

  2. Genome Sequences of Oryza Species

    KAUST Repository

    Kumagai, Masahiko

    2018-02-14

    This chapter summarizes recent data obtained from genome sequencing, annotation projects, and studies on the genome diversity of Oryza sativa and related Oryza species. O. sativa, commonly known as Asian rice, is the first monocot species whose complete genome sequence was deciphered based on physical mapping by an international collaborative effort. This genome, along with its accurate and comprehensive annotation, has become an indispensable foundation for crop genomics and breeding. With the development of innovative sequencing technologies, genomic studies of O. sativa have dramatically increased; in particular, a large number of cultivars and wild accessions have been sequenced and compared with the reference rice genome. Since de novo genome sequencing has become cost-effective, the genome of African cultivated rice, O. glaberrima, has also been determined. Comparative genomic studies have highlighted the independent domestication processes of different rice species, but it also turned out that Asian and African rice share a common gene set that has experienced similar artificial selection. An international project aimed at constructing reference genomes and examining the genome diversity of wild Oryza species is currently underway, and the genomes of some species are publicly available. This project provides a platform for investigations such as the evolution, development, polyploidization, and improvement of crops. Studies on the genomic diversity of Oryza species, including wild species, should provide new insights to solve the problem of growing food demands in the face of rapid climatic changes.

  3. Mitochondrial DNA as a non-invasive biomarker: Accurate quantification using real time quantitative PCR without co-amplification of pseudogenes and dilution bias

    International Nuclear Information System (INIS)

    Malik, Afshan N.; Shahni, Rojeen; Rodriguez-de-Ledesma, Ana; Laftah, Abas; Cunningham, Phil

    2011-01-01

    Highlights: → Mitochondrial dysfunction is central to many diseases of oxidative stress. → 95% of the mitochondrial genome is duplicated in the nuclear genome. → Dilution of untreated genomic DNA leads to dilution bias. → Unique primers and template pretreatment are needed to accurately measure mitochondrial DNA content. -- Abstract: Circulating mitochondrial DNA (MtDNA) is a potential non-invasive biomarker of cellular mitochondrial dysfunction, the latter known to be central to a wide range of human diseases. Changes in MtDNA are usually determined by quantification of MtDNA relative to nuclear DNA (Mt/N) using real time quantitative PCR. We propose that the methodology for measuring Mt/N needs to be improved and we have identified that current methods have at least one of the following three problems: (1) As much of the mitochondrial genome is duplicated in the nuclear genome, many commonly used MtDNA primers co-amplify homologous pseudogenes found in the nuclear genome; (2) use of regions from genes such as β-actin and 18S rRNA which are repetitive and/or highly variable for qPCR of the nuclear genome leads to errors; and (3) the size difference of mitochondrial and nuclear genomes cause a 'dilution bias' when template DNA is diluted. We describe a PCR-based method using unique regions in the human mitochondrial genome not duplicated in the nuclear genome; unique single copy region in the nuclear genome and template treatment to remove dilution bias, to accurately quantify MtDNA from human samples.

  4. Genome position specific priors for genomic prediction

    DEFF Research Database (Denmark)

    Brøndum, Rasmus Froberg; Su, Guosheng; Lund, Mogens Sandø

    2012-01-01

    casual mutation is different between the populations but affects the same gene. Proportions of a four-distribution mixture for SNP effects in segments of fixed size along the genome are derived from one population and set as location specific prior proportions of distributions of SNP effects...... for the target population. The model was tested using dairy cattle populations of different breeds: 540 Australian Jersey bulls, 2297 Australian Holstein bulls and 5214 Nordic Holstein bulls. The traits studied were protein-, fat- and milk yield. Genotypic data was Illumina 777K SNPs, real or imputed Results...

  5. Comparative Effectiveness Research, Genomics-Enabled Personalized Medicine, and Rapid Learning Health Care: A Common Bond

    Science.gov (United States)

    Ginsburg, Geoffrey S.; Kuderer, Nicole M.

    2012-01-01

    Despite stunning advances in our understanding of the genetics and the molecular basis for cancer, many patients with cancer are not yet receiving therapy tailored specifically to their tumor biology. The translation of these advances into clinical practice has been hindered, in part, by the lack of evidence for biomarkers supporting the personalized medicine approach. Most stakeholders agree that the translation of biomarkers into clinical care requires evidence of clinical utility. The highest level of evidence comes from randomized controlled clinical trials (RCTs). However, in many instances, there may be no RCTs that are feasible for assessing the clinical utility of potentially valuable genomic biomarkers. In the absence of RCTs, evidence generation will require well-designed cohort studies for comparative effectiveness research (CER) that link detailed clinical information to tumor biology and genomic data. CER also uses systematic reviews, evidence-quality appraisal, and health outcomes research to provide a methodologic framework for assessing biologic patient subgroups. Rapid learning health care (RLHC) is a model in which diverse data are made available, ideally in a robust and real-time fashion, potentially facilitating CER and personalized medicine. Nonetheless, to realize the full potential of personalized care using RLHC requires advances in CER and biostatistics methodology and the development of interoperable informatics systems, which has been recognized by the National Cancer Institute's program for CER and personalized medicine. The integration of CER methodology and genomics linked to RLHC should enhance, expedite, and expand the evidence generation required for fully realizing personalized cancer care. PMID:23071236

  6. Plasma proteomics to identify biomarkers - Application to cardiovascular diseases

    DEFF Research Database (Denmark)

    Beck, Hans Christian; Overgaard, Martin; Melholt Rasmussen, Lars

    2015-01-01

    There is an unmet need for new cardiovascular biomarkers. Despite this only few biomarkers for the diagnosis or screening of cardiovascular diseases have been implemented in the clinic. Thousands of proteins can be analysed in plasma by mass spectrometry-based proteomics technologies. Therefore......, this technology may therefore identify new biomarkers that previously have not been associated with cardiovascular diseases. In this review, we summarize the key challenges and considerations, including strategies, recent discoveries and clinical applications in cardiovascular proteomics that may lead...

  7. The Wide and Complex Field of NAFLD Biomarker Research: Trends

    OpenAIRE

    Wichro, Erika; Macheiner, Tanja; Schmid, Jasmin; Kavsek, Barbara; Sargsyan, Karine

    2014-01-01

    Background. Nonalcoholic fatty liver disease is now acknowledged as a complex public health issue linked to sedentary lifestyle, obesity, and related disorders like type 2 diabetes and metabolic syndrome. Aims. We aimed to retrieve its trends out of the huge amount of published data. Therefore, we conducted an extensive literature search to identify possible biomarker and/or biomarker combinations by retrospectively assessing and evaluating common and novel biomarkers to predict progression a...

  8. Identification of a biomarker panel for colorectal cancer diagnosis

    Directory of Open Access Journals (Sweden)

    García-Bilbao Amaia

    2012-01-01

    Full Text Available Abstract Background Malignancies arising in the large bowel cause the second largest number of deaths from cancer in the Western World. Despite progresses made during the last decades, colorectal cancer remains one of the most frequent and deadly neoplasias in the western countries. Methods A genomic study of human colorectal cancer has been carried out on a total of 31 tumoral samples, corresponding to different stages of the disease, and 33 non-tumoral samples. The study was carried out by hybridisation of the tumour samples against a reference pool of non-tumoral samples using Agilent Human 1A 60-mer oligo microarrays. The results obtained were validated by qRT-PCR. In the subsequent bioinformatics analysis, gene networks by means of Bayesian classifiers, variable selection and bootstrap resampling were built. The consensus among all the induced models produced a hierarchy of dependences and, thus, of variables. Results After an exhaustive process of pre-processing to ensure data quality--lost values imputation, probes quality, data smoothing and intraclass variability filtering--the final dataset comprised a total of 8, 104 probes. Next, a supervised classification approach and data analysis was carried out to obtain the most relevant genes. Two of them are directly involved in cancer progression and in particular in colorectal cancer. Finally, a supervised classifier was induced to classify new unseen samples. Conclusions We have developed a tentative model for the diagnosis of colorectal cancer based on a biomarker panel. Our results indicate that the gene profile described herein can discriminate between non-cancerous and cancerous samples with 94.45% accuracy using different supervised classifiers (AUC values in the range of 0.997 and 0.955.

  9. Impact of biomarker development on drug safety assessment

    International Nuclear Information System (INIS)

    Marrer, Estelle; Dieterle, Frank

    2010-01-01

    Drug safety has always been a key aspect of drug development. Recently, the Vioxx case and several cases of serious adverse events being linked to high-profile products have increased the importance of drug safety, especially in the eyes of drug development companies and global regulatory agencies. Safety biomarkers are increasingly being seen as helping to provide the clarity, predictability, and certainty needed to gain confidence in decision making: early-stage projects can be stopped quicker, late-stage projects become less risky. Public and private organizations are investing heavily in terms of time, money and manpower on safety biomarker development. An illustrative and 'door opening' safety biomarker success story is the recent recognition of kidney safety biomarkers for pre-clinical and limited translational contexts by FDA and EMEA. This milestone achieved for kidney biomarkers and the 'know how' acquired is being transferred to other organ toxicities, namely liver, heart, vascular system. New technologies and molecular-based approaches, i.e., molecular pathology as a complement to the classical toolbox, allow promising discoveries in the safety biomarker field. This review will focus on the utility and use of safety biomarkers all along drug development, highlighting the present gaps and opportunities identified in organ toxicity monitoring. A last part will be dedicated to safety biomarker development in general, from identification to diagnostic tests, using the kidney safety biomarkers success as an illustrative example.

  10. Imaging biomarkers as surrogate endpoints for drug development

    International Nuclear Information System (INIS)

    Richter, Wolf S.

    2006-01-01

    The employment of biomarkers (including imaging biomarkers, especially PET) in drug development has gained increasing attention during recent years. This has been partly stimulated by the hope that the integration of biomarkers into drug development programmes may be a means to increase the efficiency and effectiveness of the drug development process by early identification of promising drug candidates - thereby counteracting the rising costs of drug development. More importantly, however, the interest in biomarkers for drug development is the logical consequence of recent advances in biosciences and medicine which are leading to target-specific treatments in the framework of ''personalised medicine''. A considerable proportion of target-specific drugs will show effects in subgroups of patients only. Biomarkers are a means to identify potential responders, or patient subgroups at risk for specific side-effects. Biomarkers are used in early drug development in the context of translational medicine to gain information about the drug's potential in different patient groups and disease states. The information obtained at this stage is mainly important for designing subsequent clinical trials and to identify promising drug candidates. Biomarkers in later phases of clinical development may - if properly validated - serve as surrogate endpoints for clinical outcomes. Regulatory agencies in the EU and the USA have facilitated the use of biomarkers early in the development process. The validation of biomarkers as surrogate endpoints is part of FDA's ''critical path initiative''. (orig.)

  11. [Collaborative projects with academia for regulatory science studies on biomarkers].

    Science.gov (United States)

    Saito, Yoshiro; Nakamura, Ryosuke; Maekawa, Keiko

    2014-01-01

    Biomarkers are useful tools to be utilized as indicators/predictors of disease severity and drug responsiveness/safety, and thus are expected to promote efficient drug development and to accelerate proper use of approved drugs. Many academic achievements have been reported, but only a small number of biomarkers are used in clinical trials and drug treatments. Regulatory sciences on biomarkers for their secure development and proper qualification are necessary to facilitate their practical application. We started to collaborate with Tohoku University and Nagoya City University for sample quality, biomarker identification, evaluation of their usage, and making guidances. In this short review, scheme and progress of these projects are introduced.

  12. The economics of cardiac biomarker testing in suspected myocardial infarction.

    Science.gov (United States)

    Goodacre, Steve; Thokala, Praveen

    2015-03-01

    Suspected myocardial infarction (MI) is a common reason for emergency hospital attendance and admission. Cardiac biomarker measurement is an essential element of diagnostic assessment of suspected MI. Although the cost of a routinely available biomarker may be small, the large patient population and consequences in terms of hospital admission and investigation mean that the economic impact of cardiac biomarker testing is substantial. Economic evaluation involves comparing the estimated costs and effectiveness (outcomes) of two or more interventions or care alternatives. This process creates some difficulties with respect to cardiac biomarkers. Estimating the effectiveness of cardiac biomarkers involves identifying how they help to improve health and how we can measure this improvement. Comparison to an appropriate alternative is also problematic. New biomarkers may be promoted on the basis of reducing hospital admission or length of stay, but hospital admission for low risk patients may incur significant costs while providing very little benefit, making it an inappropriate comparator. Finally, economic evaluation may conclude that a more sensitive biomarker strategy is more effective but, by detecting and treating more cases, is also more expensive. In these circumstances it is unclear whether we should use the more effective or the cheaper option. This article provides an introduction to health economics and addresses the specific issues relevant to cardiac biomarkers. It describes the key concepts relevant to economic evaluation of cardiac biomarkers in suspected MI and highlights key areas of uncertainty and controversy. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  13. Breast Cancer Biomarkers Based on Nipple and Fine Needle Aspirates

    National Research Council Canada - National Science Library

    Torosian, Michael

    2000-01-01

    .... These biomarkers include: cytology, DNA index, cell cycle parameters, proliferation index, epidermal growth factor receptor overexpression, p53 and RAS hotspot mutations and hypermethylation of specific gene products...

  14. Genomics of Volvocine Algae

    Science.gov (United States)

    Umen, James G.; Olson, Bradley J.S.C.

    2015-01-01

    Volvocine algae are a group of chlorophytes that together comprise a unique model for evolutionary and developmental biology. The species Chlamydomonas reinhardtii and Volvox carteri represent extremes in morphological diversity within the Volvocine clade. Chlamydomonas is unicellular and reflects the ancestral state of the group, while Volvox is multicellular and has evolved numerous innovations including germ-soma differentiation, sexual dimorphism, and complex morphogenetic patterning. The Chlamydomonas genome sequence has shed light on several areas of eukaryotic cell biology, metabolism and evolution, while the Volvox genome sequence has enabled a comparison with Chlamydomonas that reveals some of the underlying changes that enabled its transition to multicellularity, but also underscores the subtlety of this transition. Many of the tools and resources are in place to further develop Volvocine algae as a model for evolutionary genomics. PMID:25883411

  15. Genomics of Preterm Birth

    Science.gov (United States)

    Swaggart, Kayleigh A.; Pavlicev, Mihaela; Muglia, Louis J.

    2015-01-01

    The molecular mechanisms controlling human birth timing at term, or resulting in preterm birth, have been the focus of considerable investigation, but limited insights have been gained over the past 50 years. In part, these processes have remained elusive because of divergence in reproductive strategies and physiology shown by model organisms, making extrapolation to humans uncertain. Here, we summarize the evolution of progesterone signaling and variation in pregnancy maintenance and termination. We use this comparative physiology to support the hypothesis that selective pressure on genomic loci involved in the timing of parturition have shaped human birth timing, and that these loci can be identified with comparative genomic strategies. Previous limitations imposed by divergence of mechanisms provide an important new opportunity to elucidate fundamental pathways of parturition control through increasing availability of sequenced genomes and associated reproductive physiology characteristics across diverse organisms. PMID:25646385

  16. Genomics of Salmonella Species

    Science.gov (United States)

    Canals, Rocio; McClelland, Michael; Santiviago, Carlos A.; Andrews-Polymenis, Helene

    Progress in the study of Salmonella survival, colonization, and virulence has increased rapidly with the advent of complete genome sequencing and higher capacity assays for transcriptomic and proteomic analysis. Although many of these techniques have yet to be used to directly assay Salmonella growth on foods, these assays are currently in use to determine Salmonella factors necessary for growth in animal models including livestock animals and in in vitro conditions that mimic many different environments. As sequencing of the Salmonella genome and microarray analysis have revolutionized genomics and transcriptomics of salmonellae over the last decade, so are new high-throughput sequencing technologies currently accelerating the pace of our studies and allowing us to approach complex problems that were not previously experimentally tractable.

  17. Developmental origins of metabolic disorders: The need for biomarker candidates and therapeutic targets from adequate preclinical models

    Directory of Open Access Journals (Sweden)

    Antonio Gonzalez-Bulnes

    2016-03-01

    Full Text Available The investigation on obesity and associated disorders have changed from an scenario in which genome drove the phenotype to a dynamic setup in which prenatal and early-postnatal conditions are determinant. However, research in human beings is difficult due to confounding factors (lifestyle and socioeconomic heterogeneity plus ethical issues. Hence, there is currently an intensive effort for developing adequate preclinical models, aiming for an adequate combination of basic studies in rodent models and specific preclinical studies in large animals. The results of these research strategies may increase the identification and development of contrasted biomarkers and therapeutic targets.

  18. CURRENT APPROACHES TO THE LABORATORY DIAGNOSIS OF RHEUMATIC DISEASES: ROLE OF MOLECULAR AND CELLULAR BIOMARKERS

    Directory of Open Access Journals (Sweden)

    E. N. Aleksandrova

    2016-01-01

    .The alternative therapies of RD include the use of low-molecular-weight chemically synthesized agents that suppress the activity of tyrosine kinases. The important area of this therapy is to restore immunological tolerance and to correct autoimmune disorders by means of autologous hematopoietic stem cells, mesenchymal stromal cells, autologous tolerogenic dendritic cells, regulatory T and B cells, gene therapy, and peptide antigens. The prospects for the laboratory diagnosis of RD are associated with the necessity of harmonizing and standardizing the current methods to determine autoantibodies and with the search for and clinical validation of novel proteomic, transcriptomic, and genomic biomarkers.

  19. Inflammasome Proteins As Biomarkers of Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Robert W. Keane

    2018-03-01

    Full Text Available Multiple sclerosis (MS is an autoimmune disease that affects the brain and spinal cord. The inflammasome is a multiprotein complex that contributes to the innate immune response in animal models of MS as well as in patients with the disease. Important to the care of patients with MS is the need for biomarkers that can predict disease onset, disease exacerbation, as well as response to treatment. In this study, we analyzed serum samples from 32 patients with MS and 120 age-matched controls, and provide receiver operator characteristic (ROC curves with associated confidence intervals following analyses of serum samples from patients with MS, most of which had the relapsing-remitting form of the disease, and from healthy unaffected donors, and determine the sensitivity and specificity of inflammasome proteins as biomarkers of MS. We report that caspase-1 (1.662 ± 0.6024 difference between means, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC (407.5 ± 35.79, and interleukin (IL-18 (78.53 + 17.86 were elevated in the serum of MS patients when compared to controls. Interestingly, the levels of IL-1β (−0.5961 ± 0.265 were lower in the MS cohort. Importantly, the area under the curve (AUC for ASC and caspase-1 were 0.9448 and 0.848, respectively. Taken together, these data suggest that ASC and caspase-1 could be potential candidate biomarkers for MS onset.

  20. Autologous Blood Transfusion in Sports: Emerging Biomarkers.

    Science.gov (United States)

    Salamin, Olivier; De Angelis, Sara; Tissot, Jean-Daniel; Saugy, Martial; Leuenberger, Nicolas

    2016-07-01

    Despite being prohibited by the World Anti-Doping Agency, blood doping through erythropoietin injection or blood transfusion is frequently used by athletes to increase oxygen delivery to muscles and enhance performance. In contrast with allogeneic blood transfusion and erythropoietic stimulants, there is presently no direct method of detection for autologous blood transfusion (ABT) doping. Blood reinfusion is currently monitored with individual follow-up of hematological variables via the athlete biological passport, which requires further improvement. Microdosage is undetectable, and suspicious profiles in athletes are often attributed to exposure to altitude, heat stress, or illness. Additional indirect biomarkers may increase the sensitivity and specificity of the longitudinal approach. The emergence of "-omics" strategies provides new opportunities to discover biomarkers for the indirect detection of ABT. With the development of direct quantitative methods, transcriptomics based on microRNA or messenger RNA expression is a promising approach. Because blood donation and blood reinfusion alter iron metabolism, quantification of proteins involved in metal metabolism, such as hepcidin, may be applied in an "ironomics" strategy to improve the detection of ABT. As red blood cell (RBC) storage triggers changes in membrane proteins, proteomic methods have the potential to identify the presence of stored RBCs in blood. Alternatively, urine matrix can be used for the quantification of the plasticizer di(2-ethyhexyl)phthalate and its metabolites that originate from blood storage bags, suggesting recent blood transfusion, and have an important degree of sensitivity and specificity. This review proposes that various indirect biomarkers should be applied in combination with mathematical approaches for longitudinal monitoring aimed at improving ABT detection. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Ebolavirus comparative genomics

    Science.gov (United States)

    Jun, Se-Ran; Leuze, Michael R.; Nookaew, Intawat; Uberbacher, Edward C.; Land, Miriam; Zhang, Qian; Wanchai, Visanu; Chai, Juanjuan; Nielsen, Morten; Trolle, Thomas; Lund, Ole; Buzard, Gregory S.; Pedersen, Thomas D.; Wassenaar, Trudy M.; Ussery, David W.

    2015-01-01

    The 2014 Ebola outbreak in West Africa is the largest documented for this virus. To examine the dynamics of this genome, we compare more than 100 currently available ebolavirus genomes to each other and to other viral genomes. Based on oligomer frequency analysis, the family Filoviridae forms a distinct group from all other sequenced viral genomes. All filovirus genomes sequenced to date encode proteins with similar functions and gene order, although there is considerable divergence in sequences between the three genera Ebolavirus, Cuevavirus and Marburgvirus within the family Filoviridae. Whereas all ebolavirus genomes are quite similar (multiple sequences of the same strain are often identical), variation is most common in the intergenic regions and within specific areas of the genes encoding the glycoprotein (GP), nucleoprotein (NP) and polymerase (L). We predict regions that could contain epitope-binding sites, which might be good vaccine targets. This information, combined with glycosylation sites and experimentally determined epitopes, can identify the most promising regions for the development of therapeutic strategies. This manuscript has been authored by UT-Battelle, LLC under Contract No. DE-AC05-00OR22725 with the U.S. Department of Energy. The United States Government retains and the publisher, by accepting the article for publication, acknowledges that the United States Government retains a non-exclusive, paid-up, irrevocable, world-wide license to publish or reproduce the published form of this manuscript, or allow others to do so, for United States Government purposes. The Department of Energy will provide public access to these results of federally sponsored research in accordance with the DOE Public Access Plan (http://energy.gov/downloads/doe-public-access-plan). PMID:26175035

  2. Brief Guide to Genomics: DNA, Genes and Genomes

    Science.gov (United States)

    ... clinic. Most new drugs based on genome-based research are estimated to be at least 10 to 15 years away, though recent genome-driven efforts in lipid-lowering therapy have considerably shortened that interval. According ...

  3. Biomarkers in chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Sin, Don D; Vestbo, Jørgen

    2009-01-01

    Currently, with exception of lung function tests, there are no well validated biomarkers or surrogate endpoints that can be used to establish efficacy of novel drugs for chronic obstructive pulmonary disease (COPD). However, the lung function test is not an ideal surrogate for short-term drug...... trials because it (1) does not provide information regarding disease activity or the underlying pathologic process, (2) cannot separate the various phenotypes of COPD, (3) is not specific for COPD, and (4) is relatively unresponsive to known therapies that prolong survival. Accordingly, there are large...

  4. Exhaled Breath Condensate for Proteomic Biomarker Discovery

    Directory of Open Access Journals (Sweden)

    Sean W. Harshman

    2014-07-01

    Full Text Available Exhaled breath condensate (EBC has been established as a potential source of respiratory biomarkers. Compared to the numerous small molecules identified, the protein content of EBC has remained relatively unstudied due to the methodological and technical difficulties surrounding EBC analysis. In this review, we discuss the proteins identified in EBC, by mass spectrometry, focusing on the significance of those proteins identified. We will also review the limitations surrounding mass spectral EBC protein analysis emphasizing recommendations to enhance EBC protein identifications by mass spectrometry. Finally, we will provide insight into the future directions of the EBC proteomics field.

  5. Metabolomics: beyond biomarkers and towards mechanisms

    Science.gov (United States)

    Johnson, Caroline H.; Ivanisevic, Julijana; Siuzdak, Gary

    2017-01-01

    Metabolomics, which is the profiling of metabolites in biofluids, cells and tissues, is routinely applied as a tool for biomarker discovery. Owing to innovative developments in informatics and analytical technologies, and the integration of orthogonal biological approaches, it is now possible to expand metabolomic analyses to understand the systems-level effects of metabolites. Moreover, because of the inherent sensitivity of metabolomics, subtle alterations in biological pathways can be detected to provide insight into the mechanisms that underlie various physiological conditions and aberrant processes, including diseases. PMID:26979502

  6. Exosomes: the future of biomarkers in medicine.

    Science.gov (United States)

    Properzi, Francesca; Logozzi, Mariantonia; Fais, Stefano

    2013-10-01

    Exosomes are nanovesicles secreted into the extracellular environment upon internal vesicle fusion with the plasma membrane. The molecular content of exosomes is a fingerprint of the releasing cell type and of its status. For this reason, and because they are released in easily accessible body fluids such as blood and urine, they represent a precious biomedical tool. A growing body of evidence suggests that exosomes may be used as biomarkers for the diagnosis and prognosis of malignant tumors. This article focuses on the exploitation of exosomes as diagnostic tools for human tumors and discusses possible applications of the same strategies to other pathologies, such as neurodegenerative diseases.

  7. Cardiac biomarkers in neonatal hypoxic ischaemia.

    LENUS (Irish Health Repository)

    Sweetman, D

    2012-04-01

    Following a perinatal hypoxic-ischaemic insult, term infants commonly develop cardiovascular dysfunction. Troponin-T, troponin-I and brain natriuretic peptide are sensitive indicators of myocardial compromise. The long-term effects of cardiovascular dysfunction on neurodevelopmental outcome following perinatal hypoxic ischaemia remain controversial. Follow-up studies are warranted to ensure optimal cardiac function in adulthood. CONCLUSION: Cardiac biomarkers may improve the diagnosis of myocardial injury, help guide management, estimate mortality risk and may also aid in longterm neurodevelopmental outcome prediction following neonatal hypoxic-ischaemia.

  8. Adiponectin as a routine clinical biomarker.

    Science.gov (United States)

    Kishida, Ken; Funahashi, Tohru; Shimomura, Iichiro

    2014-01-01

    Adiponectin is a protein synthesized and secreted predominantly by adipocytes into the peripheral blood. However, circulating adiponectin level is inversely related with body weight, especially visceral fat accumulation. The mechanism of this paradoxical relation remains obscure. Low circulating adiponectin concentrations (hypoadiponectinemia; osteoporosis, and cancer (endometrial cancer, postmenopausal breast cancer, leukemia, colon cancer, gastric cancer, prostate cancer). On the other hand, hyperadiponectinemia is associated with cardiac, renal and pulmonary diseases. This review article focuses on the significance of adiponectin as a clinical biomarker of obesity-related diseases. Routine measurement of adiponectin in patients with lifestyle-related diseases is highly recommended. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Bayesian additive decision trees of biomarker by treatment interactions for predictive biomarker detection and subgroup identification.

    Science.gov (United States)

    Zhao, Yang; Zheng, Wei; Zhuo, Daisy Y; Lu, Yuefeng; Ma, Xiwen; Liu, Hengchang; Zeng, Zhen; Laird, Glen

    2017-10-11

    Personalized medicine, or tailored therapy, has been an active and important topic in recent medical research. Many methods have been proposed in the literature for predictive biomarker detection and subgroup identification. In this article, we propose a novel decision tree-based approach applicable in randomized clinical trials. We model the prognostic effects of the biomarkers using additive regression trees and the biomarker-by-treatment effect using a single regression tree. Bayesian approach is utilized to periodically revise the split variables and the split rules of the decision trees, which provides a better overall fitting. Gibbs sampler is implemented in the MCMC procedure, which updates the prognostic trees and the interaction tree separately. We use the posterior distribution of the interaction tree to construct the predictive scores of the biomarkers and to identify the subgroup where the treatment is superior to the control. Numerical simulations show that our proposed method performs well under various settings comparing to existing methods. We also demonstrate an application of our method in a real clinical trial.

  10. Genomic Prediction in Barley

    DEFF Research Database (Denmark)

    Edriss, Vahid; Cericola, Fabio; Jensen, Jens D

    2015-01-01

    to next generation. The main goal of this study was to see the potential of using genomic prediction in a commercial Barley breeding program. The data used in this study was from Nordic Seed company which is located in Denmark. Around 350 advanced lines were genotyped with 9K Barely chip from Illumina....... Traits used in this study were grain yield, plant height and heading date. Heading date is number days it takes after 1st June for plant to head. Heritabilities were 0.33, 0.44 and 0.48 for yield, height and heading, respectively for the average of nine plots. The GBLUP model was used for genomic...

  11. Addressing small sample size bias in multiple-biomarker trials: Inclusion of biomarker-negative patients and Firth correction.

    Science.gov (United States)

    Habermehl, Christina; Benner, Axel; Kopp-Schneider, Annette

    2018-03-01

    In recent years, numerous approaches for biomarker-based clinical trials have been developed. One of these developments are multiple-biomarker trials, which aim to investigate multiple biomarkers simultaneously in independent subtrials. For low-prevalence biomarkers, small sample sizes within the subtrials have to be expected, as well as many biomarker-negative patients at the screening stage. The small sample sizes may make it unfeasible to analyze the subtrials individually. This imposes the need to develop new approaches for the analysis of such trials. With an expected large group of biomarker-negative patients, it seems reasonable to explore options to benefit from including them in such trials. We consider advantages and disadvantages of the inclusion of biomarker-negative patients in a multiple-biomarker trial with a survival endpoint. We discuss design options that include biomarker-negative patients in the study and address the issue of small sample size bias in such trials. We carry out a simulation study for a design where biomarker-negative patients are kept in the study and are treated with standard of care. We compare three different analysis approaches based on the Cox model to examine if the inclusion of biomarker-negative patients can provide a benefit with respect to bias and variance of the treatment effect estimates. We apply the Firth correction to reduce the small sample size bias. The results of the simulation study suggest that for small sample situations, the Firth correction should be applied to adjust for the small sample size bias. Additional to the Firth penalty, the inclusion of biomarker-negative patients in the analysis can lead to further but small improvements in bias and standard deviation of the estimates. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. The Biomarker Knowledge System Informatics Pilot Project Supplement To The Biomarker Development Laboratory at Moffitt (Bedlam) — EDRN Public Portal

    Science.gov (United States)

    The Biomarker Knowledge System Informatics Pilot Project goal will develop network interfaces among databases that contain information about existing clinical populations and biospecimens and data relating to those specimens that are important in biomarker assay validation. This protocol comprises one of two that will comprise the Moffitt participation in the Biomarker Knowledge System Informatics Pilot Project. THIS PROTOCOL (58) is the Sput-Epi Database.

  13. Comparative Genomics Reveals High Genomic Diversity in the Genus Photobacterium.

    Science.gov (United States)

    Machado, Henrique; Gram, Lone

    2017-01-01

    Vibrionaceae is a large marine bacterial family, which can constitute up to 50% of the prokaryotic population in marine waters. Photobacterium is the second largest genus in the family and we used comparative genomics on 35 strains representing 16 of the 28 species described so far, to understand the genomic diversity present in the Photobacterium genus. Such understanding is important for ecophysiology studies of the genus. We used whole genome sequences to evaluate phylogenetic relationships using several analyses (16S rRNA, MLSA, fur , amino-acid usage, ANI), which allowed us to identify two misidentified strains. Genome analyses also revealed occurrence of higher and lower GC content clades, correlating with phylogenetic clusters. Pan- and core-genome analysis revealed the conservation of 25% of the genome throughout the genus, with a large and open pan-genome. The major source of genomic diversity could be traced to the smaller chromosome and plasmids. Several of the physiological traits studied in the genus did not correlate with phylogenetic data. Since horizontal gene transfer (HGT) is often suggested as a source of genetic diversity and a potential driver of genomic evolution in bacterial species, we looked into evidence of such in Photobacterium genomes. Genomic islands were the source of genomic differences between strains of the same species. Also, we found transposase genes and CRISPR arrays that suggest multiple encounters with foreign DNA. Presence of genomic exchange traits was widespread and abundant in the genus, suggesting a role in genomic evolution. The high genetic variability and indications of genetic exchange make it difficult to elucidate genome evolutionary paths and raise the awareness of the roles of foreign DNA in the genomic evolution of environmental organisms.

  14. phiGENOME: an integrative navigation throughout bacteriophage genomes.

    Science.gov (United States)

    Stano, Matej; Klucar, Lubos

    2011-11-01

    phiGENOME is a web-based genome browser generating dynamic and interactive graphical representation of phage genomes stored in the phiSITE, database of gene regulation in bacteriophages. phiGENOME is an integral part of the phiSITE web portal (http://www.phisite.org/phigenome) and it was optimised for visualisation of phage genomes with the emphasis on the gene regulatory elements. phiGENOME consists of three components: (i) genome map viewer built using Adobe Flash technology, providing dynamic and interactive graphical display of phage genomes; (ii) sequence browser based on precisely formatted HTML tags, providing detailed exploration of genome features on the sequence level and (iii) regulation illustrator, based on Scalable Vector Graphics (SVG) and designed for graphical representation of gene regulations. Bringing 542 complete genome sequences accompanied with their rich annotations and references, makes phiGENOME a unique information resource in the field of phage genomics. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. P53 Gene Mutation as Biomarker of Radiation Induced Cell Injury and Genomic Instability

    International Nuclear Information System (INIS)

    Mukh-Syaifudin

    2006-01-01

    Gene expression profiling and its mutation has become one of the most widely used approaches to identify genes and their functions in the context of identify and categorize genes to be used as radiation effect markers including cell and tissue sensitivities. Ionizing radiation produces genetic damage and changes in gene expression that may lead to cancer due to specific protein that controlling cell proliferation altered the function, its expression or both. P53 protein encoded by p53 gene plays an important role in protecting cell by inducing growth arrest and or cell suicide (apoptosis) after deoxyribonucleic acid (DNA) damage induced by mutagen such as ionizing radiation. The mutant and thereby dysfunctional of this gene was found in more than 50% of various human cancers, but it is as yet unclear how p53 mutations lead to neoplastic development. Wild-type p53 has been postulated to play a role in DNA repair, suggesting that expression of mutant forms of p53 might alter cellular resistance to the DNA damage caused by radiation. Moreover, p53 is thought to function as a cell cycle checkpoint after irradiation, also suggesting that mutant p53 might change the cellular proliferative response to radiation. P53 mutations affect the cellular response to DNA damage, either by increasing DNA repair processes or, possibly, by increasing cellular tolerance to DNA damage. The association of p53 mutations with increased radioresistance suggests that alterations in the p53 gene might lead to oncogenic transformation. Current attractive model of carcinogenesis also showed that p53 gene is the major target of radiation. The majority of p53 mutations found so far is single base pair changes ( point mutations), which result in amino acid substitutions or truncated forms of the p53 protein, and are widely distributed throughout the evolutionary conserved regions of the gene. Examination of p53 mutations in human cancer also shows an association between particular carcinogens and characteristic patterns of these mutations. Even among cancers of the same organ, the mutational spectrum of the p53 gene could present different patterns by histologic subtype or risk factors and mutagen involved. (author)

  16. Integrated Genomic Biomarkers to Identify Aggressive Disease in African Americans with Prostate Cancer

    Science.gov (United States)

    2017-09-01

    Cancer” PRINCIPAL INVESTIGATOR: Dr. Albert Levin CONTRACTING ORGANIZATION: Henry Ford Health System Detroit, MI 48202 REPORT DATE: September 2017 TYPE...hfhs.org 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBER Henry Ford Health System 1...methylation sites associated with biochemical recurrence in European American men are also associated with risk of recurrence in AA men. In addition , we also

  17. Linkage of genomic biomarkers to whole organism endpoints in a Toxicity Identification Evaluation (TIE).

    Science.gov (United States)

    Aquatic organisms are exposed to many toxic chemicals and interpreting the cause and effect relationships between occurrence and impairment is difficult. Toxicity Identification Evaluation (TIE) provides a systematic approach for identifying responsible toxicants. TIE relies on ...

  18. Integrated Genomic Biomarkers to Identify Aggressive Disease in African Americans with Prostate Cancer

    Science.gov (United States)

    2016-09-01

    300 of these men; have completed pathology review of 70 of the discovery sample tumors; macrodissected and performed DNA extraction from 50 tumors...block, and sections cut and tumor areas marked by histopathologist. Target completion September 1st 2017; Discovery sample 35% completed Pathology ...African American population. Target completion March 2017; 50% completed. What was accomplished under these goals? In the current reporting

  19. Successful validation of genomic biomarkers for human immunotoxicity in Jurkat T cells in vitro.

    Science.gov (United States)

    Schmeits, Peter C J; Shao, Jia; van der Krieken, Danique A; Volger, Oscar L; van Loveren, Henk; Peijnenburg, Ad A C M; Hendriksen, Peter J M

    2015-07-01

    Previously, we identified 25 classifier genes that were able to assess immunotoxicity using human Jurkat T cells. The present study aimed to validate these classifiers. For that purpose, Jurkat cells were exposed for 6 h to subcytotoxic doses of nine immunotoxicants, five non-immunotoxicants and four compounds for which human immunotoxicity has not yet been fully established. RNA was isolated and subjected to Fluidigm quantitative real time (qRT)-PCR analysis. The sensitivity, specificity and accuracy of the screening assay as based on the nine immunotoxicants and five non-immunotoxicants used in this study were 100%, 80% and 93%, respectively, which is better than the performance in our previous study. Only one compound was classified as false positive (benzo-e-pyrene). Of the four potential (non-)immunotoxicants, chlorantraniliprole and Hidrasec were classified immunotoxic and Sunset yellow and imidacloprid as non-immunotoxic. ToxPi analysis of the PCR data provided insight in the molecular pathways that were affected by the compounds. The immunotoxicants 2,3-dichloro-propanol and cypermethrin, although structurally different, affected protein metabolism and cholesterol biosynthesis and transport. In addition, four compounds, i.e. chlorpyrifos, aldicarb, benzo-e-pyrene and anti-CD3, affected genes in cholesterol metabolism and transport, protein metabolism and transcription regulation. qRT-PCR on eight additional genes coding for similar processes as defined in ToxPi analyzes, supported these results. In conclusion, the 25 immunotoxic classifiers performed very well in a screening with new non-immunotoxic and immunotoxic compounds. Therefore, the Jurkat screening assay has great promise to be applied within a tiered approach for animal free testing of human immunotoxicity. Copyright © 2014 John Wiley & Sons, Ltd.

  20. Genome Sequencing Reveals the Environmental Origin of Enterococci and Potential Biomarkers for Water Quality Monitoring

    Science.gov (United States)

    Enterococci are common members of the gut microbiome and frequent causative agents of nosocomial infection. Because of their enteric lifestyle and ease of culturing, enterococci have been used worldwide as indicators of fecal pollution of waters. However, enterococci were recentl...

  1. Illuminating the Druggable Genome (IDG)

    Data.gov (United States)

    Federal Laboratory Consortium — Results from the Human Genome Project revealed that the human genome contains 20,000 to 25,000 genes. A gene contains (encodes) the information that each cell uses...

  2. National Human Genome Research Institute

    Science.gov (United States)

    ... Care Genomic Medicine Working Group New Horizons and Research Patient Management Policy and Ethics Issues Quick Links for Patient Care Education All About the Human Genome Project Fact Sheets Genetic Education Resources for ...

  3. Nutritional biomarkers for objective dietary assessment.

    Science.gov (United States)

    Kuhnle, Gunter G C

    2012-04-01

    The accurate assessment of dietary exposure is important in investigating associations between diet and disease. Research in nutritional epidemiology, which has resulted in a large amount of information on associations between diet and chronic diseases in the last decade, relies on accurate assessment methods to identify these associations. However, most dietary assessment instruments rely to some extent on self-reporting, which is prone to systematic bias affected by factors such as age, gender, social desirability and approval. Nutritional biomarkers are not affected by these and therefore provide an additional, alternative method to estimate intake. However, there are also some limitations in their application: they are affected by inter-individual variations in metabolism and other physiological factors, and they are often limited to estimating intake of specific compounds and not entire foods. It is therefore important to validate nutritional biomarkers to determine specific strengths and limitations. In this perspective paper, criteria for the validation of nutritional markers and future developments are discussed. Copyright © 2012 Society of Chemical Industry.

  4. Kadar Asam Urat Serum sebagai Biomarker Preeklamsi

    Directory of Open Access Journals (Sweden)

    Neli Sumanti

    2013-06-01

    Full Text Available Preeclampsia remains a health problem that becomes one of the causes of maternal deaths besides bleeding and infection. The etiology and pathogenesis of preeclampsia are unclear. Increased serum uric acid levels is seen simultaneously with the increase of blood pressure and occurred before the onset of proteinuria. Therefore, the uric acid can be used as a biomarker. The aim of this study was to analyze the serum uric acid levels between normal and preeclampsia pregnancies. The study was conducted in Dr.Hasan Sadikin Hospital Bandung between March and May 2011, using cross sectional study design. Subjects were 45 inpartu normal pregnant women as control and 44 in partu pregnant women with preeclampsia accordance with inclusion and exclusion criteria. Levels of uric acid in normal pregnancy are 3,43 ±0.14 mg/dL. In this study uric acid levels resulting in cut-off levels of 4,8 mg/dL with a sensitivity value of 93%, and specificity 80%. Conclusions: uric acid levels in at term preeclampsia are higher compared with normal pregnancies. Increased levels of uric acid can be considered as one of biomarkers of preeclampsia, hence the serum uric acid levels used as serial examinations in pregnant women during antenatal care.

  5. Metabolic Imaging Biomarkers of Postradiotherapy Xerostomia

    International Nuclear Information System (INIS)

    Cannon, Blake; Schwartz, David L.; Dong Lei

    2012-01-01

    Purpose: Xerostomia is a major complication of head and neck radiotherapy (RT). Available xerostomia measures remain flawed. [ 18 F]fluorodeoxyglucose-labeled positron emission tomography-computed tomography (FDG-PET-CT) is routinely used for staging and response assessment of head and neck cancer. We investigated quantitative measurement of parotid gland FDG uptake as a potential biomarker for post-RT xerostomia. Methods and Materials: Ninety-eight locally advanced head and neck cancer patients receiving definitive RT underwent baseline and post-RT FDG-PET-CT on a prospective imaging trial. A separate validation cohort of 14 patients underwent identical imaging while prospectively enrolled in a second trial collecting sialometry and patient-reported outcomes. Radiation dose and pre- and post-RT standard uptake values (SUVs) for all voxels contained within parotid gland ROI were deformably registered. Results: Average whole-gland or voxel-by-voxel models incorporating parotid D Met (defined as the pretreatment parotid SUV weighted by dose) accurately predicted posttreatment changes in parotid FDG uptake (e.g., fractional parotid SUV). Fractional loss of parotid FDG uptake closely paralleled early parotid toxicity defined by posttreatment salivary output (p Met may potentially be used to guide function-sparing treatment planning. Prospective validation of FDG-PET-CT as a convenient, quantifiable imaging biomarker of parotid function is warranted and ongoing.

  6. Biomarkers and Mechanisms of FANCD2 Function

    Directory of Open Access Journals (Sweden)

    Henning Willers

    2008-01-01

    Full Text Available Genetic or epigenetic inactivation of the pathway formed by the Fanconi anemia (FA and BRCA1 proteins occurs in several cancer types, making the affected tumors potentially hypersensitive to DNA cross-linkers and other chemotherapeutic agents. It has been proposed that the inability of FA/BRCA-defective cells to form subnuclear foci of effector proteins, such as FANCD2, can be used as a biomarker to aid individualization of chemotherapy. We show that FANCD2 inactivation not only renders cells sensitive to cross-links, but also oxidative stress, a common effect of cancer therapeutics. Oxidative stress sensitivity does not correlate with FANCD2 or RAD51 foci formation, but associates with increased γH2AX foci levels and apoptosis. Therefore, FANCD2 may protect cells against cross-links and oxidative stress through distinct mechanisms, consistent with the growing notion that the pathway is not linear. Our data emphasize the need for multiple biomarkers, such as γH2AX, FANCD2, and RAD51, to capture all pathway activities.

  7. Protein Biomarkers of Periodontitis in Saliva

    Science.gov (United States)

    Taylor, John J.

    2014-01-01

    Periodontitis is a chronic inflammatory condition of the tissues that surround and support the teeth and is initiated by inappropriate and excessive immune responses to bacteria in subgingival dental plaque leading to loss of the integrity of the periodontium, compromised tooth function, and eventually tooth loss. Periodontitis is an economically important disease as it is time-consuming and expensive to treat. Periodontitis has a worldwide prevalence of 5–15% and the prevalence of severe disease in western populations has increased in recent decades. Furthermore, periodontitis is more common in smokers, in obesity, in people with diabetes, and in heart disease patients although the pathogenic processes underpinning these links are, as yet, poorly understood. Diagnosis and monitoring of periodontitis rely on traditional clinical examinations which are inadequate to predict patient susceptibility, disease activity, and response to treatment. Studies of the immunopathogenesis of periodontitis and analysis of mediators in saliva have allowed the identification of many potentially useful biomarkers. Convenient measurement of these biomarkers using chairside analytical devices could form the basis for diagnostic tests which will aid the clinician and the patient in periodontitis management; this review will summarise this field and will identify the experimental, technical, and clinical issues that remain to be addressed before such tests can be implemented. PMID:24944840

  8. Sleep electroencephalography as a biomarker in depression

    Directory of Open Access Journals (Sweden)

    Steiger A

    2015-04-01

    Full Text Available Axel Steiger, Marcel Pawlowski, Mayumi Kimura Max Planck Institute of Psychiatry, Munich, Germany Abstract: The sleep electroencephalogram (EEG provides biomarkers of depression, which may help with diagnosis, prediction of therapy response, and prognosis in the treatment of depression. In patients with depression, characteristic sleep EEG changes include impaired sleep continuity, disinhibition of rapid-eye-movement (REM sleep, and impaired non-REM sleep. Most antidepressants suppress REM sleep in depressed patients, healthy volunteers, and in animal models. REM suppression appears to be an important, but not an absolute requirement, for antidepressive effects of a substance. Enhanced REM density, a measure for frequency of REM, characterizes high-risk probands for affective disorders. REM-sleep changes were also found in animal models of depression. Sleep-EEG variables were shown to predict the response to treatment with antidepressants. Furthermore, certain clusters of sleep EEG variables predicted the course of the disorder for several years. Some of the predicted sleep EEG markers appear to be related to hypothalamic–pituitary–adrenal system activity. Keywords: biomarkers, depression, sleep EEG, antidepressants, prediction, animal models

  9. Barium Titanate Nanoparticles for Biomarker Applications

    International Nuclear Information System (INIS)

    Matar, O; Hondow, N S; Brydson, R M D; Milne, S J; Brown, A P; Posada, O M; Wälti, C; Saunders, M; Murray, C A

    2015-01-01

    A tetragonal crystal structure is required for barium titanate nanoparticles to exhibit the nonlinear optical effect of second harmonic light generation (SHG) for use as a biomarker when illuminated by a near-infrared source. Here we use synchrotron XRD to elucidate the tetragonal phase of commercially purchased tetragonal, cubic and hydrothermally prepared barium titanate (BaTiO 3 ) nanoparticles by peak fitting with reference patterns. The local phase of individual nanoparticles is determined by STEM electron energy loss spectroscopy (EELS), measuring the core-loss O K-edge and the Ti L 3 -edge energy separation of the t 2g , e g peaks. The results show a change in energy separation between the t 2g and e g peak from the surface and core of the particles, suggesting an intraparticle phase mixture of the barium titanate nanoparticles. HAADF-STEM and bright field TEM-EDX show cellular uptake of the hydrothermally prepared BaTiO 3 nanoparticles, highlighting the potential for application as biomarkers. (paper)

  10. Diagnosis of Periodontal Diseases by Biomarkers

    Science.gov (United States)

    Kido, Jun-Ichi; Hino, Mami; Bando, Mika; Hiroshima, Yuka

    Many middle aged and old persons take periodontal diseases that mainly cause teeth loss and result in some systemic diseases. The prevention of periodontal diseases is very important for oral and systemic health, but the present diagnostic examination is not fully objective and suitable. To diagnose periodontal diseases exactly, some biomarkers shown inflammation, tissue degradation and bone resorption, in gingival crevicular fluid (GCF) and saliva are known. We demonstrated that GCF levels of calprotectin, inflammation-related protein, and carboxy-terminal propeptide of type I procollagen, bone metabolism-related protein, were associated with clinical condition of periodontal diseases, and suggested that these proteins may be useful biomarkers for periodontal diseases. Recently, determinations of genes and proteins by using microdevices are studied for diagnosis of some diseases. We detected calprotectin protein by chemiluminescent immunoassay on a microchip and showed the possibility of specific and quantitative detection of calprotectin in a very small amount of GCF. To determine plural markers in GCF by using microdevices contributes to develop accurate, objective diagnostic system of periodontal diseases.

  11. Retinal Layer Abnormalities as Biomarkers of Schizophrenia.

    Science.gov (United States)

    Samani, Niraj N; Proudlock, Frank A; Siram, Vasantha; Suraweera, Chathurie; Hutchinson, Claire; Nelson, Christopher P; Al-Uzri, Mohammed; Gottlob, Irene

    2018-06-06

    Schizophrenia is associated with several brain deficits, as well as visual processing deficits, but clinically useful biomarkers are elusive. We hypothesized that retinal layer changes, noninvasively visualized using spectral-domain optical coherence tomography (SD-OCT), may represent a possible "window" to these abnormalities. A Leica EnvisuTM SD-OCT device was used to obtain high-resolution central foveal B-scans in both eyes of 35 patients with schizophrenia and 50 demographically matched controls. Manual retinal layer segmentation was performed to acquire individual and combined layer thickness measurements in 3 macular regions. Contrast sensitivity was measured at 3 spatial frequencies in a subgroup of each cohort. Differences were compared using adjusted linear models and significantly different layer measures in patients underwent Spearman Rank correlations with contrast sensitivity, quantified symptoms severity, disease duration, and antipsychotic medication dose. Total retinal and photoreceptor complex thickness was reduced in all regions in patients (P layer (P layer (P layer thickness (R = -.47, P = .005). Our novel findings demonstrate considerable retinal layer abnormalities in schizophrenia that are related to clinical features and visual function. With time, SD-OCT could provide easily-measurable biomarkers to facilitate clinical assessment and further our understanding of the disease.

  12. Predicting the disease of Alzheimer with SNP biomarkers and clinical data using data mining classification approach: decision tree.

    Science.gov (United States)

    Erdoğan, Onur; Aydin Son, Yeşim

    2014-01-01

    Single Nucleotide Polymorphisms (SNPs) are the most common genomic variations where only a single nucleotide differs between individuals. Individual SNPs and SNP profiles associated with diseases can be utilized as biological markers. But there is a need to determine the SNP subsets and patients' clinical data which is informative for the diagnosis. Data mining approaches have the highest potential for extracting the knowledge from genomic datasets and selecting the representative SNPs as well as most effective and informative clinical features for the clinical diagnosis of the diseases. In this study, we have applied one of the widely used data mining classification methodology: "decision tree" for associating the SNP biomarkers and significant clinical data with the Alzheimer's disease (AD), which is the most common form of "dementia". Different tree construction parameters have been compared for the optimization, and the most accurate tree for predicting the AD is presented.

  13. Genomic prediction using subsampling.

    Science.gov (United States)

    Xavier, Alencar; Xu, Shizhong; Muir, William; Rainey, Katy Martin

    2017-03-24

    Genome-wide assisted selection is a critical tool for the genetic improvement of plants and animals. Whole-genome regression models in Bayesian framework represent the main family of prediction methods. Fitting such models with a large number of observations involves a prohibitive computational burden. We propose the use of subsampling bootstrap Markov chain in genomic prediction. Such method consists of fitting whole-genome regression models by subsampling observations in each round of a Markov Chain Monte Carlo. We evaluated the effect of subsampling bootstrap on prediction and computational parameters. Across datasets, we observed an optimal subsampling proportion of observations around 50% with replacement, and around 33% without replacement. Subsampling provided a substantial decrease in computation time, reducing the time to fit the model by half. On average, losses on predictive properties imposed by subsampling were negligible, usually below 1%. For each dataset, an optimal subsampling point that improves prediction properties was observed, but the improvements were also negligible. Combining subsampling with Gibbs sampling is an interesting ensemble algorithm. The investigation indicates that the subsampling bootstrap Markov chain algorithm substantially reduces computational burden associated with model fitting, and it may slightly enhance prediction properties.

  14. The Lotus japonicus genome

    DEFF Research Database (Denmark)

    Fabaceae, groundbreaking genetic and genomic research has established a significant body of knowledge on Lotus japonicus, which was adopted as a model species more than 20 years ago. The diverse nature of legumes means that such research has a wide potential and agricultural impact, for example...

  15. Genomic taxonomy of vibrios

    DEFF Research Database (Denmark)

    Thompson, Cristiane C.; Vicente, Ana Carolina P.; Souza, Rangel C.

    2009-01-01

    BACKGROUND: Vibrio taxonomy has been based on a polyphasic approach. In this study, we retrieve useful taxonomic information (i.e. data that can be used to distinguish different taxonomic levels, such as species and genera) from 32 genome sequences of different vibrio species. We use a variety of...

  16. The Genome Atlas Resource

    DEFF Research Database (Denmark)

    Azam Qureshi, Matloob; Rotenberg, Eva; Stærfeldt, Hans Henrik

    2010-01-01

    with scripts and algorithms developed in a variety of programming languages at the Centre for Biological Sequence Analysis in order to create a three-tier software application for genome analysis. The results are made available via a web interface developed in Java, PHP and Perl CGI. User...

  17. Genomic Signatures of Reinforcement

    Directory of Open Access Journals (Sweden)

    Austin G. Garner

    2018-04-01

    Full Text Available Reinforcement is the process by which selection against hybridization increases reproductive isolation between taxa. Much research has focused on demonstrating the existence of reinforcement, yet relatively little is known about the genetic basis of reinforcement or the evolutionary conditions under which reinforcement can occur. Inspired by reinforcement’s characteristic phenotypic pattern of reproductive trait divergence in sympatry but not in allopatry, we discuss whether reinforcement also leaves a distinct genomic pattern. First, we describe three patterns of genetic variation we expect as a consequence of reinforcement. Then, we discuss a set of alternative processes and complicating factors that may make the identification of reinforcement at the genomic level difficult. Finally, we consider how genomic analyses can be leveraged to inform if and to what extent reinforcement evolved in the face of gene flow between sympatric lineages and between allopatric and sympatric populations of the same lineage. Our major goals are to understand if genome scans for particular patterns of genetic variation could identify reinforcement, isolate the genetic basis of reinforcement, or infer the conditions under which reinforcement evolved.

  18. Better chocolate through genomics

    Science.gov (United States)

    Theobroma cacao, the cacao or chocolate tree, is a tropical understory tree whose seeds are used to make chocolate. And like any important crop, cacao is the subject of much research. On September 15, 2010, scientists publicly released a preliminary sequence of the cacao genome--which contains all o...

  19. Functional genomics of tomato

    Indian Academy of Sciences (India)

    2014-10-20

    Oct 20, 2014 ... 1Repository of Tomato Genomics Resources, Department of Plant Sciences, School .... Due to its position at the crossroads of Sanger's sequencing .... replacement for the microarray-based expression profiling. .... during RNA fragmentation step prior to library construction, ...... tomato pollen as a test case.

  20. Genomic Signatures of Reinforcement

    Science.gov (United States)

    Goulet, Benjamin E.

    2018-01-01

    Reinforcement is the process by which selection against hybridization increases reproductive isolation between taxa. Much research has focused on demonstrating the existence of reinforcement, yet relatively little is known about the genetic basis of reinforcement or the evolutionary conditions under which reinforcement can occur. Inspired by reinforcement’s characteristic phenotypic pattern of reproductive trait divergence in sympatry but not in allopatry, we discuss whether reinforcement also leaves a distinct genomic pattern. First, we describe three patterns of genetic variation we expect as a consequence of reinforcement. Then, we discuss a set of alternative processes and complicating factors that may make the identification of reinforcement at the genomic level difficult. Finally, we consider how genomic analyses can be leveraged to inform if and to what extent reinforcement evolved in the face of gene flow between sympatric lineages and between allopatric and sympatric populations of the same lineage. Our major goals are to understand if genome scans for particular patterns of genetic variation could identify reinforcement, isolate the genetic basis of reinforcement, or infer the conditions under which reinforcement evolved. PMID:29614048

  1. The Nostoc punctiforme Genome

    Energy Technology Data Exchange (ETDEWEB)

    John C. Meeks

    2001-12-31

    Nostoc punctiforme is a filamentous cyanobacterium with extensive phenotypic characteristics and a relatively large genome, approaching 10 Mb. The phenotypic characteristics include a photoautotrophic, diazotrophic mode of growth, but N. punctiforme is also facultatively heterotrophic; its vegetative cells have multiple development alternatives, including terminal differentiation into nitrogen-fixing heterocysts and transient differentiation into spore-like akinetes or motile filaments called hormogonia; and N. punctiforme has broad symbiotic competence with fungi and terrestrial plants, including bryophytes, gymnosperms and an angiosperm. The shotgun-sequencing phase of the N. punctiforme strain ATCC 29133 genome has been completed by the Joint Genome Institute. Annotation of an 8.9 Mb database yielded 7432 open reading frames, 45% of which encode proteins with known or probable known function and 29% of which are unique to N. punctiforme. Comparative analysis of the sequence indicates a genome that is highly plastic and in a state of flux, with numerous insertion sequences and multilocus repeats, as well as genes encoding transposases and DNA modification enzymes. The sequence also reveals the presence of genes encoding putative proteins that collectively define almost all characteristics of cyanobacteria as a group. N. punctiforme has an extensive potential to sense and respond to environmental signals as reflected by the presence of more than 400 genes encoding sensor protein kinases, response regulators and other transcriptional factors. The signal transduction systems and any of the large number of unique genes may play essential roles in the cell differentiation and symbiotic interaction properties of N. punctiforme.

  2. Comparative Genomics of Eukaryotes.

    NARCIS (Netherlands)

    Noort, V. van

    2007-01-01

    This thesis focuses on developing comparative genomics methods in eukaryotes, with an emphasis on applications for gene function prediction and regulatory element detection. In the past, methods have been developed to predict functional associations between gene pairs in prokaryotes. The challenge

  3. Searching for genomic constraints

    Energy Technology Data Exchange (ETDEWEB)

    Lio` , P [Cambridge, Univ. (United Kingdom). Genetics Dept.; Ruffo, S [Florence, Univ. (Italy). Fac. di Ingegneria. Dipt. di Energetica ` S. Stecco`

    1998-01-01

    The authors have analyzed general properties of very long DNA sequences belonging to simple and complex organisms, by using different correlation methods. They have distinguished those base compositional rules that concern the entire genome which they call `genomic constraints` from the rules that depend on the `external natural selection` acting on single genes, i. e. protein-centered constraints. They show that G + C content, purine / pyrimidine distributions and biological complexity of the organism are the most important factors which determine base compositional rules and genome complexity. Three main facts are here reported: bacteria with high G + C content have more restrictions on base composition than those with low G + C content; at constant G + C content more complex organisms, ranging from prokaryotes to higher eukaryotes (e.g. human) display an increase of repeats 10-20 nucleotides long, which are also partly responsible for long-range correlations; work selection of length 3 to 10 is stronger in human and in bacteria for two distinct reasons. With respect to previous studies, they have also compared the genomic sequence of the archeon Methanococcus jannaschii with those of bacteria and eukaryotes: it shows sometimes an intermediate statistical behaviour.

  4. Searching for genomic constraints

    International Nuclear Information System (INIS)

    Lio', P.; Ruffo, S.

    1998-01-01

    The authors have analyzed general properties of very long DNA sequences belonging to simple and complex organisms, by using different correlation methods. They have distinguished those base compositional rules that concern the entire genome which they call 'genomic constraints' from the rules that depend on the 'external natural selection' acting on single genes, i. e. protein-centered constraints. They show that G + C content, purine / pyrimidine distributions and biological complexity of the organism are the most important factors which determine base compositional rules and genome complexity. Three main facts are here reported: bacteria with high G + C content have more restrictions on base composition than those with low G + C content; at constant G + C content more complex organisms, ranging from prokaryotes to higher eukaryotes (e.g. human) display an increase of repeats 10-20 nucleotides long, which are also partly responsible for long-range correlations; work selection of length 3 to 10 is stronger in human and in bacteria for two distinct reasons. With respect to previous studies, they have also compared the genomic sequence of the archeon Methanococcus jannaschii with those of bacteria and eukaryotes: it shows sometimes an intermediate statistical behaviour

  5. Genomic sequencing in clinical trials

    OpenAIRE

    Mestan, Karen K; Ilkhanoff, Leonard; Mouli, Samdeep; Lin, Simon

    2011-01-01

    Abstract Human genome sequencing is the process by which the exact order of nucleic acid base pairs in the 24 human chromosomes is determined. Since the completion of the Human Genome Project in 2003, genomic sequencing is rapidly becoming a major part of our translational research efforts to understand and improve human health and disease. This article reviews the current and future directions of clinical research with respect to genomic sequencing, a technology that is just beginning to fin...

  6. Statistical Methods in Integrative Genomics

    Science.gov (United States)

    Richardson, Sylvia; Tseng, George C.; Sun, Wei

    2016-01-01

    Statistical methods in integrative genomics aim to answer important biology questions by jointly analyzing multiple types of genomic data (vertical integration) or aggregating the same type of data across multiple studies (horizontal integration). In this article, we introduce different types of genomic data and data resources, and then review statistical methods of integrative genomics, with emphasis on the motivation and rationale of these methods. We conclude with some summary points and future research directions. PMID:27482531

  7. From plant genomes to phenotypes

    OpenAIRE

    Bolger, Marie; Gundlach, Heidrun; Scholz, Uwe; Mayer, Klaus; Usadel, Björn; Schwacke, Rainer; Schmutzer, Thomas; Chen, Jinbo; Arend, Daniel; Oppermann, Markus; Weise, Stephan; Lange, Matthias; Fiorani, Fabio; Spannagl, Manuel

    2017-01-01

    Recent advances in sequencing technologies have greatly accelerated the rate of plant genome and applied breeding research. Despite this advancing trend, plant genomes continue to present numerous difficulties to the standard tools and pipelines not only for genome assembly but also gene annotation and downstream analysis.Here we give a perspective on tools, resources and services necessary to assemble and analyze plant genomes and link them to plant phenotypes.

  8. Association of SNCA with Parkinson: replication in the Harvard NeuroDiscovery Center Biomarker Study

    Science.gov (United States)

    Ding, Hongliu; Sarokhan, Alison K.; Roderick, Sarah S.; Bakshi, Rachit; Maher, Nancy E.; Ashourian, Paymon; Kan, Caroline G.; Chang, Sunny; Santarlasci, Andrea; Swords, Kyleen E.; Ravina, Bernard M.; Hayes, Michael T.; Sohur, U. Shivraj; Wills, Anne-Marie; Flaherty, Alice W.; Unni, Vivek K.; Hung, Albert Y.; Selkoe, Dennis J.; Schwarzschild, Michael A.; Schlossmacher, Michael G.; Sudarsky, Lewis R.; Growdon, John H.; Ivinson, Adrian J.; Hyman, Bradley T.; Scherzer, Clemens R.

    2011-01-01

    Background Mutations in the α-synuclein gene (SNCA) cause autosomal dominant forms of Parkinson’s disease, but the substantial risk conferred by this locus to the common sporadic disease has only recently emerged from genome-wide association studies. Methods Here we genotyped a prioritized non-coding variant in SNCA intron-4 in 344 patients with Parkinson’s and 275 controls from the longitudinal Harvard NeuroDiscovery Center Biomarker Study. Results The common minor allele of rs2736990 was associated with elevated disease susceptibility (odds ratio = 1.40, P value = 0.0032). Conclusions This result increases confidence in the notion that in many clinically well-characterized patients genetic variation in SNCA contributes to “sporadic” disease. PMID:21953863

  9. Biomarker discovery and applications for foods and beverages: proteomics to nanoproteomics.

    Science.gov (United States)

    Agrawal, Ganesh Kumar; Timperio, Anna Maria; Zolla, Lello; Bansal, Vipul; Shukla, Ravi; Rakwal, Randeep

    2013-11-20

    Foods and beverages have been at the heart of our society for centuries, sustaining humankind - health, life, and the pleasures that go with it. The more we grow and develop as a civilization, the more we feel the need to know about the food we eat and beverages we drink. Moreover, with an ever increasing demand for food due to the growing human population food security remains a major concern. Food safety is another growing concern as the consumers prefer varied foods and beverages that are not only traded nationally but also globally. The 21st century science and technology is at a new high, especially in the field of biological sciences. The availability of genome sequences and associated high-throughput sensitive technologies means that foods are being analyzed at various levels. For example and in particular, high-throughput omics approaches are being applied to develop suitable biomarkers for foods and beverages and their applications in addressing quality, technology, authenticity, and safety issues. Proteomics are one of those technologies that are increasingly being utilized to profile expressed proteins in different foods and beverages. Acquired knowledge and protein information have now been translated to address safety of foods and beverages. Very recently, the power of proteomic technology has been integrated with another highly sensitive and miniaturized technology called nanotechnology, yielding a new term nanoproteomics. Nanoproteomics offer a real-time multiplexed analysis performed in a miniaturized assay, with low-sample consumption and high sensitivity. To name a few, nanomaterials - quantum dots, gold nanoparticles, carbon nanotubes, and nanowires - have demonstrated potential to overcome the challenges of sensitivity faced by proteomics for biomarker detection, discovery, and application. In this review, we will discuss the importance of biomarker discovery and applications for foods and beverages, the contribution of proteomic technology in

  10. The potential role for use of mitochondrial DNA copy number as predictive biomarker in presbycusis.

    Science.gov (United States)

    Falah, Masoumeh; Houshmand, Massoud; Najafi, Mohammad; Balali, Maryam; Mahmoudian, Saeid; Asghari, Alimohamad; Emamdjomeh, Hessamaldin; Farhadi, Mohammad

    2016-01-01

    Age-related hearing impairment, or presbycusis, is the most common communication disorder and neurodegenerative disease in the elderly. Its prevalence is expected to increase, due to the trend of growth of the elderly population. The current diagnostic test for detection of presbycusis is implemented after there has been a change in hearing sensitivity. Identification of a pre-diagnostic biomarker would raise the possibility of preserving hearing sensitivity before damage occurs. Mitochondrial dysfunction, including the production of reactive oxygen species and induction of expression of apoptotic genes, participates in the progression of presbycusis. Mitochondrial DNA sequence variation has a critical role in presbycusis. However, the nature of the relationship between mitochondrial DNA copy number, an important biomarker in many other diseases, and presbycusis is undetermined. Fifty-four subjects with presbycusis and 29 healthy controls were selected after ear, nose, throat examination and pure-tone audiometry. DNA was extracted from peripheral blood samples. The copy number of mitochondrial DNA relative to the nuclear genome was measured by quantitative real-time polymerase chain reaction. Subjects with presbycusis had a lower median mitochondrial DNA copy number than healthy subjects and the difference was statistically significant ( P =0.007). Mitochondrial DNA copy number was also significantly associated with degree of hearing impairment ( P =0.025) and audiogram configuration ( P =0.022). The findings of this study suggest that lower mitochondrial DNA copy number is responsible for presbycusis through alteration of mitochondrial function. Moreover, the significant association of mitochondrial DNA copy number in peripheral blood samples with the degree of hearing impairment and audiogram configuration has potential for use as a standard test for presbycusis, providing the possibility of the development of an easy-to-use biomarker for the early detection of

  11. Biomarkers for early and late stage chronic allograft nephropathy by proteogenomic profiling of peripheral blood.

    Directory of Open Access Journals (Sweden)

    Sunil M Kurian

    2009-07-01

    Full Text Available Despite significant improvements in life expectancy of kidney transplant patients due to advances in surgery and immunosuppression, Chronic Allograft Nephropathy (CAN remains a daunting problem. A complex network of cellular mechanisms in both graft and peripheral immune compartments complicates the non-invasive diagnosis of CAN, which still requires biopsy histology. This is compounded by non-immunological factors contributing to graft injury. There is a pressing need to identify and validate minimally invasive biomarkers for CAN to serve as early predictors of graft loss and as metrics for managing long-term immunosuppression.We used DNA microarrays, tandem mass spectroscopy proteomics and bioinformatics to identify genomic and proteomic markers of mild and moderate/severe CAN in peripheral blood of two distinct cohorts (n = 77 total of kidney transplant patients with biopsy-documented histology.Gene expression profiles reveal over 2400 genes for mild CAN, and over 700 for moderate/severe CAN. A consensus analysis reveals 393 (mild and 63 (moderate/severe final candidates as CAN markers with predictive accuracy of 80% (mild and 92% (moderate/severe. Proteomic profiles show over 500 candidates each, for both stages of CAN including 302 proteins unique to mild and 509 unique to moderate/severe CAN.This study identifies several unique signatures of transcript and protein biomarkers with high predictive accuracies for mild and moderate/severe CAN, the most common cause of late allograft failure. These biomarkers are the necessary first step to a proteogenomic classification of CAN based on peripheral blood profiling and will be the targets of a prospective clinical validation study.

  12. CSF biomarker variability in the Alzheimer's Association quality control program

    NARCIS (Netherlands)

    Mattsson, N.; Andreasson, U.; Persson, S.; Carrillo, M.C.; Collins, S.; Chalbot, S.; Cutler, N.; Dufour-Rainfray, D.; Fagan, A.M.; Heegaard, N.H.H.; Robin Hsiung, G.Y.; Hyman, B.; Iqbal, K.; Lachno, D.R.; Lleo, A.; Lewczuk, P.; Molinuevo, J.L.; Parchi, P.; Regeniter, A.; Rissman, R.; Rosenmann, H.; Sancesario, G.; Schroder, J.; Shaw, L.M.; Teunissen, C.E.; Trojanowski, J.Q.; Vanderstichele, H.; Vandijck, M.; Verbeek, M.M.; Zetterberg, H.; Blennow, K.; Kaser, S.A.; et al.,

    2013-01-01

    BACKGROUND: The cerebrospinal fluid (CSF) biomarkers amyloid beta 1-42, total tau, and phosphorylated tau are used increasingly for Alzheimer's disease (AD) research and patient management. However, there are large variations in biomarker measurements among and within laboratories. METHODS: Data

  13. CSF biomarker variability in the Alzheimer's Association quality control program

    NARCIS (Netherlands)

    Mattsson, N.; Andreasson, U.; Persson, S.; Carrillo, M.C.; Collins, S.; Chalbot, S.; Cutler, N.; Dufour-Rainfray, D.; Fagan, A.M.; Heegaard, N.H.H.; Hsiung, G.Y.R.; Hyman, B.; Iqbal, K.; Lachno, D.R.; Lleo, A.; Lewczuk, P.; Molinuevo, J.L.; Parchi, P.; Regeniter, A.; Rissman, R.; Rosenmann, H.; Sancesario, G.; Schroder, J.; Shaw, L.M.; Teunissen, C.E.; Trojanowski, J.Q.; Vanderstichele, H.; Vandijck, M.; Verbeek, M.M.; Zetterberg, H.; Blennow, K.; Kaser, S.A.

    2013-01-01

    Background: The cerebrospinal fluid (CSF) biomarkers amyloid beta 1-42, total tau, and phosphorylated tau are used increasingly for Alzheimer's disease (AD) research and patient management. However, there are large variations in biomarker measurements among and within laboratories. Methods: Data

  14. Cardiovascular biomarkers and sex: the case for women.

    Science.gov (United States)

    Daniels, Lori B; Maisel, Alan S

    2015-10-01

    Measurement of biomarkers is a critical component of cardiovascular care. Women and men differ in their cardiac physiology and manifestations of cardiovascular disease. Although most cardiovascular biomarkers are used by clinicians without taking sex into account, sex-specific differences in biomarkers clearly exist. Baseline concentrations of many biomarkers (including cardiac troponin, natriuretic peptides, galectin-3, and soluble ST2) differ in men versus women, but these sex-specific differences do not generally translate into a need for differential sex-based cut-off points. Furthermore, most biomarkers are similarly diagnostic and prognostic, regardless of sex. Two potential exceptions are cardiac troponins measured by high-sensitivity assay, and proneurotensin. Troponin levels are lower in women than in men and, with the use of high-sensitivity assays, sex-specific cut-off points might improve the diagnosis of myocardial infarction. Proneurotensin is a novel biomarker that was found to be predictive of incident cardiovascular disease in women, but not men, and was also predictive of incident breast cancer. If confirmed, proneurotensin might be a unique biomarker of disease risk in women. With any biomarker, an understanding of sex-specific differences might improve its use and might also lead to an enhanced understanding of the physiological differences between the hearts of men and women.

  15. Application of bio-marker to study on tumor radiosensitivity

    International Nuclear Information System (INIS)

    Guo Wanfeng; Ding Guirong; Han Liangfu

    2001-01-01

    To definite tumor radiosensitivity is important for applying the schedules of individualization of patient radiotherapy. Many laboratories were carrying on the research which predict the tumor radiosensitivity with one bio-marker or/and multi-bio-marker in various levels. At present has not witnessed the specific bio-marker, but it provides an excellent model for predicting tumor radiosensitivity

  16. Metabolomics as a tool in the identification of dietary biomarkers.

    Science.gov (United States)

    Gibbons, Helena; Brennan, Lorraine

    2017-02-01

    Current dietary assessment methods including FFQ, 24-h recalls and weighed food diaries are associated with many measurement errors. In an attempt to overcome some of these errors, dietary biomarkers have emerged as a complementary approach to these traditional methods. Metabolomics has developed as a key technology for the identification of new dietary biomarkers and to date, metabolomic-based approaches have led to the identification of a number of putative biomarkers. The three approaches generally employed when using metabolomics in dietary biomarker discovery are: (i) acute interventions where participants consume specific amounts of a test food, (ii) cohort studies where metabolic profiles are compared between consumers and non-consumers of a specific food and (iii) the analysis of dietary patterns and metabolic profiles to identify nutritypes and biomarkers. The present review critiques the current literature in terms of the approaches used for dietary biomarker discovery and gives a detailed overview of the currently proposed biomarkers, highlighting steps needed for their full validation. Furthermore, the present review also evaluates areas such as current databases and software tools, which are needed to advance the interpretation of results and therefore enhance the utility of dietary biomarkers in nutrition research.

  17. Oxidative stress biomarkers in Oreochromis niloticus as early ...

    African Journals Online (AJOL)

    2018-04-10

    Apr 10, 2018 ... warning signals in assessing pollution from acid mine drainage and ... fish species Oreochromis niloticus as a bio-indicator organism in active ... Key water quality parameters, including ... Biomarkers can provide early warning of potential higher- ...... CT (2001) The use of biomarkers in Ecological Risk.

  18. The future of blood-based biomarkers for Alzheimer's disease

    DEFF Research Database (Denmark)

    Henriksen, Kim; O'Bryant, Sid E; Hampel, Harald

    2014-01-01

    Treatment of Alzheimer's disease (AD) is significantly hampered by the lack of easily accessible biomarkers that can detect disease presence and predict disease risk reliably. Fluid biomarkers of AD currently provide indications of disease stage; however, they are not robust predictors of disease...

  19. Cancer Biomarker Discovery: Lectin-Based Strategies Targeting Glycoproteins

    Directory of Open Access Journals (Sweden)

    David Clark

    2012-01-01

    Full Text Available Biomarker discovery can identify molecular markers in various cancers that can be used for detection, screening, diagnosis, and monitoring of disease progression. Lectin-affinity is a technique that can be used for the enrichment of glycoproteins from a complex sample, facilitating the discovery of novel cancer biomarkers associated with a disease state.

  20. Biomarker-guided repurposing of chemotherapeutic drugs for cancer therapy

    DEFF Research Database (Denmark)

    Stenvang, Jan; Kümler, Iben; Nygård, Sune Boris

    2013-01-01

    -standard chemotherapeutic drug will be relatively low in such a patient cohort it is a pre-requisite that such testing is based on predictive biomarkers. This review describes our strategy of biomarker-guided repurposing of chemotherapeutic drugs for cancer therapy, taking the repurposing of topoisomerase I (Top1...

  1. Glycosylation-Based Serum Biomarkers for Cancer Diagnostics and Prognostics.

    Science.gov (United States)

    Kirwan, Alan; Utratna, Marta; O'Dwyer, Michael E; Joshi, Lokesh; Kilcoyne, Michelle

    2015-01-01

    Cancer is the second most common cause of death in developed countries with approximately 14 million newly diagnosed individuals and over 6 million cancer-related deaths in 2012. Many cancers are discovered at a more advanced stage but better survival rates are correlated with earlier detection. Current clinically approved cancer biomarkers are most effective when applied to patients with widespread cancer. Single biomarkers with satisfactory sensitivity and specificity have not been identified for the most common cancers and some biomarkers are ineffective for the detection of early stage cancers. Thus, novel biomarkers with better diagnostic and prognostic performance are required. Aberrant protein glycosylation is well known hallmark of cancer and represents a promising source of potential biomarkers. Glycoproteins enter circulation from tissues or blood cells through active secretion or leakage and patient serum is an attractive option as a source for biomarkers from a clinical and diagnostic perspective. A plethora of technical approaches have been developed to address the challenges of glycosylation structure detection and determination. This review summarises currently utilised glycoprotein biomarkers and novel glycosylation-based biomarkers from the serum glycoproteome under investigation as cancer diagnostics and for monitoring and prognostics and includes details of recent high throughput and other emerging glycoanalytical techniques.

  2. A tuberculosis biomarker database: the key to novel TB diagnostics

    Directory of Open Access Journals (Sweden)

    Seda Yerlikaya

    2017-03-01

    Full Text Available New diagnostic innovations for tuberculosis (TB, including point-of-care solutions, are critical to reach the goals of the End TB Strategy. However, despite decades of research, numerous reports on new biomarker candidates, and significant investment, no well-performing, simple and rapid TB diagnostic test is yet available on the market, and the search for accurate, non-DNA biomarkers remains a priority. To help overcome this ‘biomarker pipeline problem’, FIND and partners are working on the development of a well-curated and user-friendly TB biomarker database. The web-based database will enable the dynamic tracking of evidence surrounding biomarker candidates in relation to target product profiles (TPPs for needed TB diagnostics. It will be able to accommodate raw datasets and facilitate the verification of promising biomarker candidates and the identification of novel biomarker combinations. As such, the database will simplify data and knowledge sharing, empower collaboration, help in the coordination of efforts and allocation of resources, streamline the verification and validation of biomarker candidates, and ultimately lead to an accelerated translation into clinically useful tools.

  3. Biomarkers in Prodromal Parkinson Disease: a Qualitative Review.

    Science.gov (United States)

    Cooper, Christine A; Chahine, Lama M

    2016-11-01

    Over the past several years, the concept of prodromal Parkinson disease (PD) has been increasingly recognized. This term refers to individuals who do not fulfill motor diagnostic criteria for PD, but who have clinical, genetic, or biomarker characteristics suggesting risk of developing PD in the future. Clinical diagnosis of prodromal PD has low specificity, prompting the need for objective biomarkers with higher specificity. In this qualitative review, we discuss objectively defined putative biomarkers for PD and prodromal PD. We searched Pubmed and Embase for articles pertaining to objective biomarkers for PD and their application in prodromal cohorts. Articles were selected based on relevance and methodology. Objective biomarkers of demonstrated utility in prodromal PD include ligand-based imaging and transcranial sonography. Development of serum, cerebrospinal fluid, and tissue-based biomarkers is underway, but their application in prodromal PD has yet to meaningfully occur. Combining objective biomarkers with clinical or genetic prodromal features increases the sensitivity and specificity for identifying prodromal PD. Several objective biomarkers for prodromal PD show promise but require further study, including their application to and validation in prodromal cohorts followed longitudinally. Accurate identification of prodromal PD will likely require a multimodal approach. (JINS, 2016, 22, 956-967).

  4. Haematological and serum enzymes biomarkers of heavy metals in ...

    African Journals Online (AJOL)

    Haematological and serum enzymes biomarkers of heavy metals in Chrysichthys Nigrodigitatus and Cynoglossus senegalensis. ... Haematological and serum enzymes activities are predilective biomarkers for the detection and monitoring of aquatic ecosystems pollution. The inclusion of Allium sativum at 1.5g/kg is ...

  5. Imperfect Gold Standards for Kidney Injury Biomarker Evaluation

    Science.gov (United States)

    Betensky, Rebecca A.; Emerson, Sarah C.; Bonventre, Joseph V.

    2012-01-01

    Clinicians have used serum creatinine in diagnostic testing for acute kidney injury for decades, despite its imperfect sensitivity and specificity. Novel tubular injury biomarkers may revolutionize the diagnosis of acute kidney injury; however, even if a novel tubular injury biomarker is 100% sensitive and 100% specific, it may appear inaccurate when using serum creatinine as the gold standard. Acute kidney injury, as defined by serum creatinine, may not reflect tubular injury, and the absence of changes in serum creatinine does not assure the absence of tubular injury. In general, the apparent diagnostic performance of a biomarker depends not only on its ability to detect injury, but also on disease prevalence and the sensitivity and specificity of the imperfect gold standard. Assuming that, at a certain cutoff value, serum creatinine is 80% sensitive and 90% specific and disease prevalence is 10%, a new perfect biomarker with a true 100% sensitivity may seem to have only 47% sensitivity compared with serum creatinine as the gold standard. Minimizing misclassification by using more strict criteria to diagnose acute kidney injury will reduce the error when evaluating the performance of a biomarker under investigation. Apparent diagnostic errors using a new biomarker may be a reflection of errors in the imperfect gold standard itself, rather than poor performance of the biomarker. The results of this study suggest that small changes in serum creatinine alone should not be used to define acute kidney injury in biomarker or interventional studies. PMID:22021710

  6. Biomarker Detection in Association Studies: Modeling SNPs Simultaneously via Logistic ANOVA

    KAUST Repository

    Jung, Yoonsuh; Huang, Jianhua Z.; Hu, Jianhua

    2014-01-01

    In genome-wide association studies, the primary task is to detect biomarkers in the form of Single Nucleotide Polymorphisms (SNPs) that have nontrivial associations with a disease phenotype and some other important clinical/environmental factors. However, the extremely large number of SNPs comparing to the sample size inhibits application of classical methods such as the multiple logistic regression. Currently the most commonly used approach is still to analyze one SNP at a time. In this paper, we propose to consider the genotypes of the SNPs simultaneously via a logistic analysis of variance (ANOVA) model, which expresses the logit transformed mean of SNP genotypes as the summation of the SNP effects, effects of the disease phenotype and/or other clinical variables, and the interaction effects. We use a reduced-rank representation of the interaction-effect matrix for dimensionality reduction, and employ the L 1-penalty in a penalized likelihood framework to filter out the SNPs that have no associations. We develop a Majorization-Minimization algorithm for computational implementation. In addition, we propose a modified BIC criterion to select the penalty parameters and determine the rank number. The proposed method is applied to a Multiple Sclerosis data set and simulated data sets and shows promise in biomarker detection.

  7. Recent mass spectrometry-based proteomics for biomarker discovery in lung cancer, COPD, and asthma.

    Science.gov (United States)

    Fujii, Kiyonaga; Nakamura, Haruhiko; Nishimura, Toshihide

    2017-04-01

    Lung cancer and related diseases have been one of the most common causes of deaths worldwide. Genomic-based biomarkers may hardly reflect the underlying dynamic molecular mechanism of functional protein interactions, which is the center of a disease. Recent developments in mass spectrometry (MS) have made it possible to analyze disease-relevant proteins expressed in clinical specimens by proteomic challenges. Areas covered: To understand the molecular mechanisms of lung cancer and its subtypes, chronic obstructive pulmonary disease (COPD), asthma and others, great efforts have been taken to identify numerous relevant proteins by MS-based clinical proteomic approaches. Since lung cancer is a multifactorial disease that is biologically associated with asthma and COPD among various lung diseases, this study focused on proteomic studies on biomarker discovery using various clinical specimens for lung cancer, COPD, and asthma. Expert commentary: MS-based exploratory proteomics utilizing clinical specimens, which can incorporate both experimental and bioinformatic analysis of protein-protein interaction and also can adopt proteogenomic approaches, makes it possible to reveal molecular networks that are relevant to a disease subgroup and that could differentiate between drug responders and non-responders, good and poor prognoses, drug resistance, and so on.

  8. Ribosomal proteins as biomarkers for bacterial identification by mass spectrometry in the clinical microbiology laboratory.

    Science.gov (United States)

    Suarez, Stéphanie; Ferroni, Agnès; Lotz, Aurélie; Jolley, Keith A; Guérin, Philippe; Leto, Julie; Dauphin, Brunhilde; Jamet, Anne; Maiden, Martin C J; Nassif, Xavier; Armengaud, Jean

    2013-09-01

    Whole-cell matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) is a rapid method for identification of microorganisms that is increasingly used in microbiology laboratories. This identification is based on the comparison of the tested isolate mass spectrum with reference databases. Using Neisseria meningitidis as a model organism, we showed that in one of the available databases, the Andromas database, 10 of the 13 species-specific biomarkers correspond to ribosomal proteins. Remarkably, one biomarker, ribosomal protein L32, was subject to inter-strain variability. The analysis of the ribosomal protein patterns of 100 isolates for which whole genome sequences were available, confirmed the presence of inter-strain variability in the molecular weight of 29 ribosomal proteins, thus establishing a correlation between the sequence type (ST) and/or clonal complex (CC) of each strain and its ribosomal protein pattern. Since the molecular weight of three of the variable ribosomal proteins (L30, L31 and L32) was included in the spectral window observed by MALDI-TOF MS in clinical microbiology, i.e., 3640-12000 m/z, we were able by analyzing the molecular weight of these three ribosomal proteins to classify each strain in one of six subgroups, each of these subgroups corresponding to specific STs and/or CCs. Their detection by MALDI-TOF allows therefore a quick typing of N. meningitidis isolates. © 2013 Elsevier B.V. All rights reserved.

  9. Biomarker Detection in Association Studies: Modeling SNPs Simultaneously via Logistic ANOVA

    KAUST Repository

    Jung, Yoonsuh

    2014-10-02

    In genome-wide association studies, the primary task is to detect biomarkers in the form of Single Nucleotide Polymorphisms (SNPs) that have nontrivial associations with a disease phenotype and some other important clinical/environmental factors. However, the extremely large number of SNPs comparing to the sample size inhibits application of classical methods such as the multiple logistic regression. Currently the most commonly used approach is still to analyze one SNP at a time. In this paper, we propose to consider the genotypes of the SNPs simultaneously via a logistic analysis of variance (ANOVA) model, which expresses the logit transformed mean of SNP genotypes as the summation of the SNP effects, effects of the disease phenotype and/or other clinical variables, and the interaction effects. We use a reduced-rank representation of the interaction-effect matrix for dimensionality reduction, and employ the L 1-penalty in a penalized likelihood framework to filter out the SNPs that have no associations. We develop a Majorization-Minimization algorithm for computational implementation. In addition, we propose a modified BIC criterion to select the penalty parameters and determine the rank number. The proposed method is applied to a Multiple Sclerosis data set and simulated data sets and shows promise in biomarker detection.

  10. Epigenetic Biomarkers of Breast Cancer Risk: Across the Breast Cancer Prevention Continuum.

    Science.gov (United States)

    Terry, Mary Beth; McDonald, Jasmine A; Wu, Hui Chen; Eng, Sybil; Santella, Regina M

    2016-01-01

    Epigenetic biomarkers, such as DNA methylation, can increase cancer risk through altering gene expression. The Cancer Genome Atlas (TCGA) Network has demonstrated breast cancer-specific DNA methylation signatures. DNA methylation signatures measured at the time of diagnosis may prove important for treatment options and in predicting disease-free and overall survival (tertiary prevention). DNA methylation measurement in cell free DNA may also be useful in improving early detection by measuring tumor DNA released into the blood (secondary prevention). Most evidence evaluating the use of DNA methylation markers in tertiary and secondary prevention efforts for breast cancer comes from studies that are cross-sectional or retrospective with limited corresponding epidemiologic data, raising concerns about temporality. Few prospective studies exist that are large enough to address whether DNA methylation markers add to the prediction of tertiary and secondary outcomes over and beyond standard clinical measures. Determining the role of epigenetic biomarkers in primary prevention can help in identifying modifiable pathways for targeting interventions and reducing disease incidence. The potential is great for DNA methylation markers to improve cancer outcomes across the prevention continuum. Large, prospective epidemiological studies will provide essential evidence of the overall utility of adding these markers to primary prevention efforts, screening, and clinical care.

  11. Investigation of serum biomarkers in primary gout patients using iTRAQ-based screening.

    Science.gov (United States)

    Ying, Ying; Chen, Yong; Zhang, Shun; Huang, Haiyan; Zou, Rouxin; Li, Xiaoke; Chu, Zanbo; Huang, Xianqian; Peng, Yong; Gan, Minzhi; Geng, Baoqing; Zhu, Mengya; Ying, Yinyan; Huang, Zuoan

    2018-03-21

    Primary gout is a major disease that affects human health; however, its pathogenesis is not well known. The purpose of this study was to identify biomarkers to explore the underlying mechanisms of primary gout. We used the isobaric tags for relative and absolute quantitation (iTRAQ) technique combined with liquid chromatography-tandem mass spectrometry to screen differentially expressed proteins between gout patients and controls. We also identified proteins potentially involved in gout pathogenesis by analysing biological processes, cellular components, molecular functions, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and protein-protein interactions. We further verified some samples using enzyme-linked immunosorbent assay (ELISA). Statistical analyses were carried out using SPSS v. 20.0 and ROC (receiver operating characterstic) curve analyses were carried out using Medcalc software. Two-sided p-values gout than in controls (p=0.023). iTRAQ technology was useful in the selection of differentially expressed proteins from proteomes, and provides a strong theoretical basis for the study of biomarkers and mechanisms in primary gout. In addition, TBB4A protein may be associated with primary gout.

  12. A Thousand Fly Genomes: An Expanded Drosophila Genome Nexus.

    Science.gov (United States)

    Lack, Justin B; Lange, Jeremy D; Tang, Alison D; Corbett-Detig, Russell B; Pool, John E

    2016-12-01

    The Drosophila Genome Nexus is a population genomic resource that provides D. melanogaster genomes from multiple sources. To facilitate comparisons across data sets, genomes are aligned using a common reference alignment pipeline which involves two rounds of mapping. Regions of residual heterozygosity, identity-by-descent, and recent population admixture are annotated to enable data filtering based on the user's needs. Here, we present a significant expansion of the Drosophila Genome Nexus, which brings the current data object to a total of 1,121 wild-derived genomes. New additions include 305 previously unpublished genomes from inbred lines representing six population samples in Egypt, Ethiopia, France, and South Africa, along with another 193 genomes added from recently-published data sets. We also provide an aligned D. simulans genome to facilitate divergence comparisons. This improved resource will broaden the range of population genomic questions that can addressed from multi-population allele frequencies and haplotypes in this model species. The larger set of genomes will also enhance the discovery of functionally relevant natural variation that exists within and between populations. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  13. Toxicogenomic multigene biomarker for predicting the future onset of proximal tubular injury in rats

    International Nuclear Information System (INIS)

    Minowa, Yohsuke; Kondo, Chiaki; Uehara, Takeki; Morikawa, Yuji; Okuno, Yasushi; Nakatsu, Noriyuki; Ono, Atsushi; Maruyama, Toshiyuki; Kato, Ikuo; Yamate, Jyoji; Yamada, Hiroshi; Ohno, Yasuo; Urushidani, Tetsuro

    2012-01-01

    Drug-induced renal tubular injury is a major concern in the preclinical safety evaluation of drug candidates. Toxicogenomics is now a generally accepted tool for identifying chemicals with potential safety problems. The specific aim of the present study was to develop a model for use in predicting the future onset of drug-induced proximal tubular injury following repeated dosing with various nephrotoxicants. In total, 41 nephrotoxic and nonnephrotoxic compounds were used for the present analysis. Male Sprague-Dawley rats were dosed orally or intravenously once daily. Animals were exposed to three different doses (low, middle, and high) of each compound, and kidney tissue was collected at 3, 6, 9, and 24 h after single dosing, and on days 4, 8, 15, and 29 after repeated dosing. Gene expression profiles were generated from kidney total RNA using Affymetrix DNA microarrays. Filter-type gene selection and linear classification algorithms were employed to discriminate future onset of proximal tubular injury. We identified genomic biomarkers for use in future onset prediction using the gene expression profiles determined on day 1, when most of the nephrotoxicants had yet to produce detectable histopathological changes. The model was evaluated using a five-fold cross validation, and achieved a sensitivity of 93% and selectivity of 90% with 19 probes. We also found that the prediction accuracy of the optimized model was substantially higher than that produced by any of the single genomic biomarkers or histopathology. The genes included in our model were primarily involved in DNA replication, cell cycle control, apoptosis, and responses to oxidative stress and chemical stimuli. In summary, our toxicogenomic model is particularly useful for predicting the future onset of proximal tubular injury.

  14. Novel biomarkers for prediabetes, diabetes, and associated complications

    Science.gov (United States)

    Dorcely, Brenda; Katz, Karin; Jagannathan, Ram; Chiang, Stephanie S; Oluwadare, Babajide; Goldberg, Ira J; Bergman, Michael

    2017-01-01

    The number of individuals with prediabetes is expected to grow substantially and estimated to globally affect 482 million people by 2040. Therefore, effective methods for diagnosing prediabetes will be required to reduce the risk of progressing to diabetes and its complications. The current biomarkers, glycated hemoglobin (HbA1c), fructosamine, and glycated albumin have limitations including moderate sensitivity and specificity and are inaccurate in certain clinical conditions. Therefore, identification of additional biomarkers is being explored recognizing that any single biomarker will also likely have inherent limitations. Therefore, combining several biomarkers may more precisely identify those at high risk for developing prediabetes and subsequent progression to diabetes. This review describes recently identified biomarkers and their potential utility for addressing the burgeoning epidemic of dysglycemic disorders. PMID:28860833

  15. Biomarkers of acute lung injury: worth their salt?

    Directory of Open Access Journals (Sweden)

    Proudfoot Alastair G

    2011-12-01

    Full Text Available Abstract The validation of biomarkers has become a key goal of translational biomedical research. The purpose of this article is to discuss the role of biomarkers in the management of acute lung injury (ALI and related research. Biomarkers should be sensitive and specific indicators of clinically important processes and should change in a relevant timeframe to affect recruitment to trials or clinical management. We do not believe that they necessarily need to reflect pathogenic processes. We critically examined current strategies used to identify biomarkers and which, owing to expedience, have been dominated by reanalysis of blood derived markers from large multicenter Phase 3 studies. Combining new and existing validated biomarkers with physiological and other data may add predictive power and facilitate the development of important aids to research and therapy.

  16. Can Biomarkers Help the Early Diagnosis of Parkinson's Disease?

    Institute of Scientific and Technical Information of China (English)

    Weidong Le; Jie Dong; Song Li; Amos D.Korczyn

    2017-01-01

    Parkinson's disease (PD) is a complex neurodegenerative disease with progressive loss of dopamine neurons.PD patients usually manifest a series of motor and non-motor symptoms.In order to provide better early diagnosis and subsequent disease-modifying therapies for PD patients,there is an urgent need to identify sensitive and specific biomarkers.Biomarkers can be divided into four categories:clinical,imaging,biochemical,and genetic.Ideal biomarkers not only improve our understanding of PD pathogenesis and progression,but also provide benefits for early risk evaluation and clinical diagnosis of PD.Although many efforts have been made and several biomarkers have been extensively investigated,few if any have been found useful for early diagnosis.Here,we summarize recent developments in the discovered biomarkers of PD and discuss their merits and limitations for the early diagnosis of PD.

  17. Possible biomarkers modulating haloperidol efficacy and/or tolerability.

    Science.gov (United States)

    Porcelli, Stefano; Crisafulli, Concetta; Calabrò, Marco; Serretti, Alessandro; Rujescu, Dan

    2016-04-01

    Haloperidol (HP) is widely used in the treatment of several forms of psychosis. Despite of its efficacy, HP use is a cause of concern for the elevated risk of adverse drug reactions. adverse drug reactions risk and HP efficacy greatly vary across subjects, indicating the involvement of several factors in HP mechanism of action. The use of biomarkers that could monitor or even predict HP treatment impact would be of extreme importance. We reviewed the elements that could potentially be used as peripheral biomarkers of HP effectiveness. Although a validated biomarker still does not exist, we underlined the several potential findings (e.g., about cytokines, HP metabolites and genotypic biomarkers) which could pave the way for future research on HP biomarkers.

  18. The New Digital Divide For Digital BioMarkers.

    Science.gov (United States)

    Torous, John; Rodriguez, Jorge; Powell, Adam

    2017-09-01

    As smartphone and sensors continue to become more ubiquitous across the world, digital biomarkers have emerged as a scalable and practical tool to explore disease states and advance health. But as the digital divide of access and ownership begins to fade, a new digital divide is emerging. Who are the types of people that own smartphones or smart watches, who are the types of people that download health apps or partake in digital biomarker studies, and who are the types of people that are actually active with digital biomarkers apps and sensors - the people providing the high quality and longitudinal data that this field is being founded upon? Understanding the people behind digital biomarkers, the very people this emerging field aims to help, may actually be the real challenge as well as opportunity for digital biomarkers.

  19. Target biomarker profile for the clinical management of paracetamol overdose

    Science.gov (United States)

    Vliegenthart, A D Bastiaan; Antoine, Daniel J; Dear, James W

    2015-01-01

    Paracetamol (acetaminophen) overdose is one of the most common causes of acute liver injury in the Western world. To improve patient care and reduce pressure on already stretched health care providers new biomarkers are needed that identify or exclude liver injury soon after an overdose of paracetamol is ingested. This review highlights the current state of paracetamol poisoning management and how novel biomarkers could improve patient care and save healthcare providers money. Based on the widely used concept of defining a target product profile, a target biomarker profile is proposed that identifies desirable and acceptable key properties for a biomarker in development to enable the improved treatment of this patient population. The current biomarker candidates, with improved hepatic specificity and based on the fundamental mechanistic basis of paracetamol-induced liver injury, are reviewed and their performance compared with our target profile. PMID:26076366

  20. Biomarker assessment and molecular testing for prognostication in breast cancer.

    Science.gov (United States)

    Kos, Zuzana; Dabbs, David J

    2016-01-01

    Current treatment of breast cancer incorporates clinical, pathological and molecular data. Oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) define prognosis and identify tumours for targeted therapy, and remain the sole established single-molecule biomarkers defining the minimum breast cancer pathology data set. Ki67 remains one of the most promising yet controversial biomarkers in breast cancer, implemented routinely in some, but not all, pathology departments. Beyond the single-molecule biomarkers, a host of multigene expression tests have been developed to interrogate the driver pathways and biology of individual breast cancers to predict clinical outcome more accurately. A minority of these assays have entered into clinical practice. This review focuses on the established biomarkers of ER, PR and HER2, the controversial but clinically implemented biomarker Ki67 and the currently marketed gene expression signatures. © 2015 John Wiley & Sons Ltd.