RADIA: RNA and DNA integrated analysis for somatic mutation detection.

Directory of Open Access Journals (Sweden)

Amie J Radenbaugh

Full Text Available The detection of somatic single nucleotide variants is a crucial component to the characterization of the cancer genome. Mutation calling algorithms thus far have focused on comparing the normal and tumor genomes from the same individual. In recent years, it has become routine for projects like The Cancer Genome Atlas (TCGA to also sequence the tumor RNA. Here we present RADIA (RNA and DNA Integrated Analysis, a novel computational method combining the patient-matched normal and tumor DNA with the tumor RNA to detect somatic mutations. The inclusion of the RNA increases the power to detect somatic mutations, especially at low DNA allelic frequencies. By integrating an individual's DNA and RNA, we are able to detect mutations that would otherwise be missed by traditional algorithms that examine only the DNA. We demonstrate high sensitivity (84% and very high precision (98% and 99% for RADIA in patient data from endometrial carcinoma and lung adenocarcinoma from TCGA. Mutations with both high DNA and RNA read support have the highest validation rate of over 99%. We also introduce a simulation package that spikes in artificial mutations to patient data, rather than simulating sequencing data from a reference genome. We evaluate sensitivity on the simulation data and demonstrate our ability to rescue back mutations at low DNA allelic frequencies by including the RNA. Finally, we highlight mutations in important cancer genes that were rescued due to the incorporation of the RNA.

Phylogenetic turnover during subtropical forest succession across environmental and phylogenetic scales.

Science.gov (United States)

Purschke, Oliver; Michalski, Stefan G; Bruelheide, Helge; Durka, Walter

2017-12-01

Although spatial and temporal patterns of phylogenetic community structure during succession are inherently interlinked and assembly processes vary with environmental and phylogenetic scales, successional studies of community assembly have yet to integrate spatial and temporal components of community structure, while accounting for scaling issues. To gain insight into the processes that generate biodiversity after disturbance, we combine analyses of spatial and temporal phylogenetic turnover across phylogenetic scales, accounting for covariation with environmental differences. We compared phylogenetic turnover, at the species- and individual-level, within and between five successional stages, representing woody plant communities in a subtropical forest chronosequence. We decomposed turnover at different phylogenetic depths and assessed its covariation with between-plot abiotic differences. Phylogenetic turnover between stages was low relative to species turnover and was not explained by abiotic differences. However, within the late-successional stages, there was high presence-/absence-based turnover (clustering) that occurred deep in the phylogeny and covaried with environmental differentiation. Our results support a deterministic model of community assembly where (i) phylogenetic composition is constrained through successional time, but (ii) toward late succession, species sorting into preferred habitats according to niche traits that are conserved deep in phylogeny, becomes increasingly important.

Pan-Cancer Mutational and Transcriptional Analysis of the Integrator Complex

Directory of Open Access Journals (Sweden)

Antonio Federico

2017-04-01

Full Text Available The integrator complex has been recently identified as a key regulator of RNA Polymerase II-mediated transcription, with many functions including the processing of small nuclear RNAs, the pause-release and elongation of polymerase during the transcription of protein coding genes, and the biogenesis of enhancer derived transcripts. Moreover, some of its components also play a role in genome maintenance. Thus, it is reasonable to hypothesize that their functional impairment or altered expression can contribute to malignancies. Indeed, several studies have described the mutations or transcriptional alteration of some Integrator genes in different cancers. Here, to draw a comprehensive pan-cancer picture of the genomic and transcriptomic alterations for the members of the complex, we reanalyzed public data from The Cancer Genome Atlas. Somatic mutations affecting Integrator subunit genes and their transcriptional profiles have been investigated in about 11,000 patients and 31 tumor types. A general heterogeneity in the mutation frequencies was observed, mostly depending on tumor type. Despite the fact that we could not establish them as cancer drivers, INTS7 and INTS8 genes were highly mutated in specific cancers. A transcriptome analysis of paired (normal and tumor samples revealed that the transcription of INTS7, INTS8, and INTS13 is significantly altered in several cancers. Experimental validation performed on primary tumors confirmed these findings.

Towards an integrated phylogenetic classification of the Tremellomycetes.

Science.gov (United States)

Liu, X-Z; Wang, Q-M; Göker, M; Groenewald, M; Kachalkin, A V; Lumbsch, H T; Millanes, A M; Wedin, M; Yurkov, A M; Boekhout, T; Bai, F-Y

2015-06-01

Families and genera assigned to Tremellomycetes have been mainly circumscribed by morphology and for the yeasts also by biochemical and physiological characteristics. This phenotype-based classification is largely in conflict with molecular phylogenetic analyses. Here a phylogenetic classification framework for the Tremellomycetes is proposed based on the results of phylogenetic analyses from a seven-genes dataset covering the majority of tremellomycetous yeasts and closely related filamentous taxa. Circumscriptions of the taxonomic units at the order, family and genus levels recognised were quantitatively assessed using the phylogenetic rank boundary optimisation (PRBO) and modified general mixed Yule coalescent (GMYC) tests. In addition, a comprehensive phylogenetic analysis on an expanded LSU rRNA (D1/D2 domains) gene sequence dataset covering as many as available teleomorphic and filamentous taxa within Tremellomycetes was performed to investigate the relationships between yeasts and filamentous taxa and to examine the stability of undersampled clades. Based on the results inferred from molecular data and morphological and physiochemical features, we propose an updated classification for the Tremellomycetes. We accept five orders, 17 families and 54 genera, including seven new families and 18 new genera. In addition, seven families and 17 genera are emended and one new species name and 185 new combinations are proposed. We propose to use the term pro tempore or pro tem. in abbreviation to indicate the species names that are temporarily maintained.

BIMLR: a method for constructing rooted phylogenetic networks from rooted phylogenetic trees.

Science.gov (United States)

Wang, Juan; Guo, Maozu; Xing, Linlin; Che, Kai; Liu, Xiaoyan; Wang, Chunyu

2013-09-15

Rooted phylogenetic trees constructed from different datasets (e.g. from different genes) are often conflicting with one another, i.e. they cannot be integrated into a single phylogenetic tree. Phylogenetic networks have become an important tool in molecular evolution, and rooted phylogenetic networks are able to represent conflicting rooted phylogenetic trees. Hence, the development of appropriate methods to compute rooted phylogenetic networks from rooted phylogenetic trees has attracted considerable research interest of late. The CASS algorithm proposed by van Iersel et al. is able to construct much simpler networks than other available methods, but it is extremely slow, and the networks it constructs are dependent on the order of the input data. Here, we introduce an improved CASS algorithm, BIMLR. We show that BIMLR is faster than CASS and less dependent on the input data order. Moreover, BIMLR is able to construct much simpler networks than almost all other methods. BIMLR is available at http://nclab.hit.edu.cn/wangjuan/BIMLR/. © 2013 Elsevier B.V. All rights reserved.

Integration of Digital Dental Casts in Cone-Beam Computed Tomography Scans

Science.gov (United States)

Rangel, Frits A.; Maal, Thomas J. J.; Bergé, Stefaan J.; Kuijpers-Jagtman, Anne Marie

2012-01-01

Cone-beam computed tomography (CBCT) is widely used in maxillofacial surgery. The CBCT image of the dental arches, however, is of insufficient quality to use in digital planning of orthognathic surgery. Several authors have described methods to integrate digital dental casts into CBCT scans, but all reported methods have drawbacks. The aim of this feasibility study is to present a new simplified method to integrate digital dental casts into CBCT scans. In a patient scheduled for orthognathic surgery, titanium markers were glued to the gingiva. Next, a CBCT scan and dental impressions were made. During the impression-taking procedure, the titanium markers were transferred to the impression. The impressions were scanned, and all CBCT datasets were exported in DICOM format. The two datasets were matched, and the dentition derived from the scanned impressions was transferred to the CBCT of the patient. After matching the two datasets, the average distance between the corresponding markers was 0.1 mm. This novel method allows for the integration of digital dental casts into CBCT scans, overcoming problems such as unwanted extra radiation exposure, distortion of soft tissues due to the use of bite jigs, and time-consuming digital data handling. PMID:23050159

Deep mutational scanning identifies sites in influenza nucleoprotein that affect viral inhibition by MxA.

Directory of Open Access Journals (Sweden)

Orr Ashenberg

2017-03-01

Full Text Available The innate-immune restriction factor MxA inhibits influenza replication by targeting the viral nucleoprotein (NP. Human influenza virus is more resistant than avian influenza virus to inhibition by human MxA, and prior work has compared human and avian viral strains to identify amino-acid differences in NP that affect sensitivity to MxA. However, this strategy is limited to identifying sites in NP where mutations that affect MxA sensitivity have fixed during the small number of documented zoonotic transmissions of influenza to humans. Here we use an unbiased deep mutational scanning approach to quantify how all single amino-acid mutations to NP affect MxA sensitivity in the context of replication-competent virus. We both identify new sites in NP where mutations affect MxA resistance and re-identify mutations known to have increased MxA resistance during historical adaptations of influenza to humans. Most of the sites where mutations have the greatest effect are almost completely conserved across all influenza A viruses, and the amino acids at these sites confer relatively high resistance to MxA. These sites cluster in regions of NP that appear to be important for its recognition by MxA. Overall, our work systematically identifies the sites in influenza nucleoprotein where mutations affect sensitivity to MxA. We also demonstrate a powerful new strategy for identifying regions of viral proteins that affect inhibition by host factors.

Mutational scanning reveals the determinants of protein insertion and association energetics in the plasma membrane.

Science.gov (United States)

Elazar, Assaf; Weinstein, Jonathan; Biran, Ido; Fridman, Yearit; Bibi, Eitan; Fleishman, Sarel Jacob

2016-01-29

Insertion of helix-forming segments into the membrane and their association determines the structure, function, and expression levels of all plasma membrane proteins. However, systematic and reliable quantification of membrane-protein energetics has been challenging. We developed a deep mutational scanning method to monitor the effects of hundreds of point mutations on helix insertion and self-association within the bacterial inner membrane. The assay quantifies insertion energetics for all natural amino acids at 27 positions across the membrane, revealing that the hydrophobicity of biological membranes is significantly higher than appreciated. We further quantitate the contributions to membrane-protein insertion from positively charged residues at the cytoplasm-membrane interface and reveal large and unanticipated differences among these residues. Finally, we derive comprehensive mutational landscapes in the membrane domains of Glycophorin A and the ErbB2 oncogene, and find that insertion and self-association are strongly coupled in receptor homodimers.

Fourier transform inequalities for phylogenetic trees.

Science.gov (United States)

Matsen, Frederick A

2009-01-01

Phylogenetic invariants are not the only constraints on site-pattern frequency vectors for phylogenetic trees. A mutation matrix, by its definition, is the exponential of a matrix with non-negative off-diagonal entries; this positivity requirement implies non-trivial constraints on the site-pattern frequency vectors. We call these additional constraints "edge-parameter inequalities". In this paper, we first motivate the edge-parameter inequalities by considering a pathological site-pattern frequency vector corresponding to a quartet tree with a negative internal edge. This site-pattern frequency vector nevertheless satisfies all of the constraints described up to now in the literature. We next describe two complete sets of edge-parameter inequalities for the group-based models; these constraints are square-free monomial inequalities in the Fourier transformed coordinates. These inequalities, along with the phylogenetic invariants, form a complete description of the set of site-pattern frequency vectors corresponding to bona fide trees. Said in mathematical language, this paper explicitly presents two finite lists of inequalities in Fourier coordinates of the form "monomial < or = 1", each list characterizing the phylogenetically relevant semialgebraic subsets of the phylogenetic varieties.

Stenostomum cf. leucops (Platyhelminthes in Thailand: a surface observation using scanning electron microscopy and phylogenetic analysis based on 18S ribosomal DNA sequences

Directory of Open Access Journals (Sweden)

Arin Ngamniyom

2016-02-01

Full Text Available The genus Stenostomum contains small turbellaria that are widely distributed in freshwater environments worldwide. However, there are only rare reports or studies of this genus from Thailand. Therefore, the objective of this study was to report S. cf. leucops in Thailand collected from Pathum Thani Province. The worm morphology and surface topography using scanning electron microscopy were determined. Moreover, the phylogenetic tree of S. cf. leucops was analysed with 17 flatworms based on the 18S ribosomal DNA sequences. The phylogenetic relationship shared a common ancestry of Catenulida species, and S. cf. leucops displayed a monophyletic pattern within Stenostomum spp. The results of the morphological and molecular data are discussed. These results may increase the knowledge of freshwater microturbellarians in Thailand.

Mutation scanning analysis of genetic variation within and among Echinococcus species: implications and future prospects.

Science.gov (United States)

Jabbar, Abdul; Gasser, Robin B

2013-07-01

Adult tapeworms of the genus Echinococcus (family Taeniidae) occur in the small intestines of carnivorous definitive hosts and are transmitted to particular intermediate mammalian hosts, in which they develop as fluid-filled larvae (cysts) in internal organs (usually lung and liver), causing the disease echinococcosis. Echinococcus species are of major medical importance and also cause losses to the meat and livestock industries, mainly due to the condemnation of infected offal. Decisions regarding the treatment and control of echinococcosis rely on the accurate identification of species and population variants (strains). Conventional, phenetic methods for specific identification have some significant limitations. Despite advances in the development of molecular tools, there has been limited application of mutation scanning methods to species of Echinococcus. Here, we briefly review key genetic markers used for the identification of Echinococcus species and techniques for the analysis of genetic variation within and among populations, and the diagnosis of echinococcosis. We also discuss the benefits of utilizing mutation scanning approaches to elucidate the population genetics and epidemiology of Echinococcus species. These benefits are likely to become more evident following the complete characterization of the genomes of E. granulosus and E. multilocularis.

An Improved Binary Differential Evolution Algorithm to Infer Tumor Phylogenetic Trees.

Science.gov (United States)

Liang, Ying; Liao, Bo; Zhu, Wen

2017-01-01

Tumourigenesis is a mutation accumulation process, which is likely to start with a mutated founder cell. The evolutionary nature of tumor development makes phylogenetic models suitable for inferring tumor evolution through genetic variation data. Copy number variation (CNV) is the major genetic marker of the genome with more genes, disease loci, and functional elements involved. Fluorescence in situ hybridization (FISH) accurately measures multiple gene copy number of hundreds of single cells. We propose an improved binary differential evolution algorithm, BDEP, to infer tumor phylogenetic tree based on FISH platform. The topology analysis of tumor progression tree shows that the pathway of tumor subcell expansion varies greatly during different stages of tumor formation. And the classification experiment shows that tree-based features are better than data-based features in distinguishing tumor. The constructed phylogenetic trees have great performance in characterizing tumor development process, which outperforms other similar algorithms.

Phylogenetic tests of distribution patterns in South Asia: towards

Indian Academy of Sciences (India)

The last four decades have seen an increasing integration of phylogenetics and biogeography. However, a dearth of phylogenetic studies has precluded such biogeographic analyses in South Asia until recently. Noting the increase in phylogenetic research and interest in phylogenetic biogeography in the region, we ...

Design of Test Wrapper Scan Chain Based on Differential Evolution

Directory of Open Access Journals (Sweden)

Aijun Zhu

2013-08-01

Full Text Available Integrated Circuit has entered the era of design of the IP-based SoC (System on Chip, which makes the IP core reuse become a key issue. SoC test wrapper design for scan chain is a NP Hard problem, we propose an algorithm based on Differential Evolution (DE to design wrapper scan chain. Through group’s mutation, crossover and selection operations, the design of test wrapper scan chain is achieved. Experimental verification is carried out according to the international standard benchmark ITC’02. The results show that the algorithm can obtain shorter longest wrapper scan chains, compared with other algorithms.

Integration of Digital Dental Casts in Cone-Beam Computed Tomography Scans

OpenAIRE

Rangel, Frits A.; Maal, Thomas J. J.; Bergé, Stefaan J.; Kuijpers-Jagtman, Anne Marie

2012-01-01

Cone-beam computed tomography (CBCT) is widely used in maxillofacial surgery. The CBCT image of the dental arches, however, is of insufficient quality to use in digital planning of orthognathic surgery. Several authors have described methods to integrate digital dental casts into CBCT scans, but all reported methods have drawbacks. The aim of this feasibility study is to present a new simplified method to integrate digital dental casts into CBCT scans. In a patient scheduled for orthognathic ...

End-to-End Traffic Flow Modeling of the Integrated SCaN Network

Science.gov (United States)

Cheung, K.-M.; Abraham, D. S.

2012-05-01

In this article, we describe the analysis and simulation effort of the end-to-end traffic flow for the Integrated Space Communications and Navigation (SCaN) Network. Using the network traffic derived for the 30-day period of July 2018 from the Space Communications Mission Model (SCMM), we generate the wide-area network (WAN) bandwidths of the ground links for different architecture options of the Integrated SCaN Network. We also develop a new analytical scheme to model the traffic flow and buffering mechanism of a store-and-forward network. It is found that the WAN bandwidth of the Integrated SCaN Network is an important differentiator of different architecture options, as the recurring circuit costs of certain architecture options can be prohibitively high.

Identifiability of tree-child phylogenetic networks under a probabilistic recombination-mutation model of evolution.

Science.gov (United States)

Francis, Andrew; Moulton, Vincent

2018-06-07

Phylogenetic networks are an extension of phylogenetic trees which are used to represent evolutionary histories in which reticulation events (such as recombination and hybridization) have occurred. A central question for such networks is that of identifiability, which essentially asks under what circumstances can we reliably identify the phylogenetic network that gave rise to the observed data? Recently, identifiability results have appeared for networks relative to a model of sequence evolution that generalizes the standard Markov models used for phylogenetic trees. However, these results are quite limited in terms of the complexity of the networks that are considered. In this paper, by introducing an alternative probabilistic model for evolution along a network that is based on some ground-breaking work by Thatte for pedigrees, we are able to obtain an identifiability result for a much larger class of phylogenetic networks (essentially the class of so-called tree-child networks). To prove our main theorem, we derive some new results for identifying tree-child networks combinatorially, and then adapt some techniques developed by Thatte for pedigrees to show that our combinatorial results imply identifiability in the probabilistic setting. We hope that the introduction of our new model for networks could lead to new approaches to reliably construct phylogenetic networks. Copyright © 2018 Elsevier Ltd. All rights reserved.

Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer

NARCIS (Netherlands)

Peifer, Martin; Fernandez-Cuesta, Lynnette; Sos, Martin L.; George, Julie; Seidel, Danila; Kasper, Lawryn H.; Plenker, Dennis; Leenders, Frauke; Sun, Ruping; Zander, Thomas; Menon, Roopika; Koker, Mirjam; Dahmen, Ilona; Mueller, Christian; Di Cerbo, Vincenzo; Schildhaus, Hans-Ulrich; Altmueller, Janine; Baessmann, Ingelore; Becker, Christian; de Wilde, Bram; Vandesompele, Jo; Boehm, Diana; Ansen, Sascha; Gabler, Franziska; Wilkening, Ines; Heynck, Stefanie; Heuckmann, Johannes M.; Lu, Xin; Carter, Scott L.; Cibulskis, Kristian; Banerji, Shantanu; Getz, Gad; Park, Kwon-Sik; Rauh, Daniel; Gruetter, Christian; Fischer, Matthias; Pasqualucci, Laura; Wright, Gavin; Wainer, Zoe; Russell, Prudence; Petersen, Iver; Chen, Yuan; Stoelben, Erich; Ludwig, Corinna; Schnabel, Philipp; Hoffmann, Hans; Muley, Thomas; Brockmann, Michael; Engel-Riedel, Walburga; Muscarella, Lucia A.; Fazio, Vito M.; Groen, Harry; Timens, Wim; Sietsma, Hannie; Thunnissen, Erik; Smit, Egbert; Heideman, Danielle A. M.; Snijders, Peter J. F.; Cappuzzo, Federico; Ligorio, Claudia; Damiani, Stefania; Field, John; Solberg, Steinar; Brustugun, Odd Terje; Lund-Iversen, Marius; Saenger, Joerg; Clement, Joachim H.; Soltermann, Alex; Moch, Holger; Weder, Walter; Solomon, Benjamin; Soria, Jean-Charles; Validire, Pierre; Besse, Benjamin; Brambilla, Elisabeth; Brambilla, Christian; Lantuejoul, Sylvie; Lorimier, Philippe; Schneider, Peter M.; Hallek, Michael; Pao, William; Meyerson, Matthew; Sage, Julien; Shendure, Jay; Schneider, Robert; Buettner, Reinhard; Wolf, Juergen; Nuernberg, Peter; Perner, Sven; Heukamp, Lukas C.; Brindle, Paul K.; Haas, Stefan; Thomas, Roman K.

2012-01-01

Small-cell lung cancer (SCLC) is an aggressive lung tumor subtype with poor prognosis(1-3). We sequenced 29 SCLC exomes, 2 genomes and 15 transcriptomes and found an extremely high mutation rate of 7.4 +/- 1 protein-changing mutations per million base pairs. Therefore, we conducted integrated

Functional and phylogenetic ecology in R

CERN Document Server

Swenson, Nathan G

2014-01-01

Functional and Phylogenetic Ecology in R is designed to teach readers to use R for phylogenetic and functional trait analyses. Over the past decade, a dizzying array of tools and methods were generated to incorporate phylogenetic and functional information into traditional ecological analyses. Increasingly these tools are implemented in R, thus greatly expanding their impact. Researchers getting started in R can use this volume as a step-by-step entryway into phylogenetic and functional analyses for ecology in R. More advanced users will be able to use this volume as a quick reference to understand particular analyses. The volume begins with an introduction to the R environment and handling relevant data in R. Chapters then cover phylogenetic and functional metrics of biodiversity; null modeling and randomizations for phylogenetic and functional trait analyses; integrating phylogenetic and functional trait information; and interfacing the R environment with a popular C-based program. This book presents a uni...

The phylogenetic likelihood library.

Science.gov (United States)

Flouri, T; Izquierdo-Carrasco, F; Darriba, D; Aberer, A J; Nguyen, L-T; Minh, B Q; Von Haeseler, A; Stamatakis, A

2015-03-01

We introduce the Phylogenetic Likelihood Library (PLL), a highly optimized application programming interface for developing likelihood-based phylogenetic inference and postanalysis software. The PLL implements appropriate data structures and functions that allow users to quickly implement common, error-prone, and labor-intensive tasks, such as likelihood calculations, model parameter as well as branch length optimization, and tree space exploration. The highly optimized and parallelized implementation of the phylogenetic likelihood function and a thorough documentation provide a framework for rapid development of scalable parallel phylogenetic software. By example of two likelihood-based phylogenetic codes we show that the PLL improves the sequential performance of current software by a factor of 2-10 while requiring only 1 month of programming time for integration. We show that, when numerical scaling for preventing floating point underflow is enabled, the double precision likelihood calculations in the PLL are up to 1.9 times faster than those in BEAGLE. On an empirical DNA dataset with 2000 taxa the AVX version of PLL is 4 times faster than BEAGLE (scaling enabled and required). The PLL is available at http://www.libpll.org under the GNU General Public License (GPL). © The Author(s) 2014. Published by Oxford University Press, on behalf of the Society of Systematic Biologists.

Integrated Automatic Workflow for Phylogenetic Tree Analysis Using Public Access and Local Web Services.

Science.gov (United States)

Damkliang, Kasikrit; Tandayya, Pichaya; Sangket, Unitsa; Pasomsub, Ekawat

2016-11-28

At the present, coding sequence (CDS) has been discovered and larger CDS is being revealed frequently. Approaches and related tools have also been developed and upgraded concurrently, especially for phylogenetic tree analysis. This paper proposes an integrated automatic Taverna workflow for the phylogenetic tree inferring analysis using public access web services at European Bioinformatics Institute (EMBL-EBI) and Swiss Institute of Bioinformatics (SIB), and our own deployed local web services. The workflow input is a set of CDS in the Fasta format. The workflow supports 1,000 to 20,000 numbers in bootstrapping replication. The workflow performs the tree inferring such as Parsimony (PARS), Distance Matrix - Neighbor Joining (DIST-NJ), and Maximum Likelihood (ML) algorithms of EMBOSS PHYLIPNEW package based on our proposed Multiple Sequence Alignment (MSA) similarity score. The local web services are implemented and deployed into two types using the Soaplab2 and Apache Axis2 deployment. There are SOAP and Java Web Service (JWS) providing WSDL endpoints to Taverna Workbench, a workflow manager. The workflow has been validated, the performance has been measured, and its results have been verified. Our workflow's execution time is less than ten minutes for inferring a tree with 10,000 replicates of the bootstrapping numbers. This paper proposes a new integrated automatic workflow which will be beneficial to the bioinformaticians with an intermediate level of knowledge and experiences. All local services have been deployed at our portal http://bioservices.sci.psu.ac.th.

Scanning electron microscopy of male terminalia and its application to species recognition and phylogenetic reconstruction in the Drosophila saltans group.

Science.gov (United States)

Souza, Tiago Alves Jorge; Noll, Fernando Barbosa; Bicudo, Hermione Elly Melara de Campos; Madi-Ravazzi, Lilian

2014-01-01

The Drosophila saltans group consists of five subgroups and 21 species, most of which have been identified only by morphological aspects of the male terminalia revealed by drawings using a camera lucida and a bright-field microscope. However, several species in the group, mainly those included in the saltans subgroup, are difficult to differentiate using only these characteristics. In this study, we used scanning electron microscopy (SEM) to analyze 19 structures of the male terminalia in 10 species from the five saltans subgroups. Among these structures, nine could be identified only through SEM analysis. We aimed to find other characteristics useful for morphological recognition of these species and to use these characteristics for phylogenetic reconstruction. These morphological differences enabled us to effectively distinguish among sibling species. These findings confirmed the monophyly of this group as previously determined in evolutionary studies based on other markers. The single most parsimonious tree (CI = 87 and RI = 90) indicated that the cordata subgroup is the most basal lineage and the saltans subgroup is the most apical lineage, as shown in earlier studies based on morphological data. However, our findings differed somewhat from these studies with respect to the phylogenetic relationships of species in the saltans group indicating that this group is still a puzzle that remains to be deciphered.

Power Measurements for Microvision, Inc., Aircrew Integrated Helmet System Scanning Laser Helmet-Mounted Display

National Research Council Canada - National Science Library

Rash, Clarence

2002-01-01

...) technology based on scanning lasers. Under this program, Microvision, Inc., Bothell, Washington, has developed a scanning laser HMD prototype for use with the Aircrew Integrated Helmet System (AIHS...

treespace: Statistical exploration of landscapes of phylogenetic trees.

Science.gov (United States)

Jombart, Thibaut; Kendall, Michelle; Almagro-Garcia, Jacob; Colijn, Caroline

2017-11-01

The increasing availability of large genomic data sets as well as the advent of Bayesian phylogenetics facilitates the investigation of phylogenetic incongruence, which can result in the impossibility of representing phylogenetic relationships using a single tree. While sometimes considered as a nuisance, phylogenetic incongruence can also reflect meaningful biological processes as well as relevant statistical uncertainty, both of which can yield valuable insights in evolutionary studies. We introduce a new tool for investigating phylogenetic incongruence through the exploration of phylogenetic tree landscapes. Our approach, implemented in the R package treespace, combines tree metrics and multivariate analysis to provide low-dimensional representations of the topological variability in a set of trees, which can be used for identifying clusters of similar trees and group-specific consensus phylogenies. treespace also provides a user-friendly web interface for interactive data analysis and is integrated alongside existing standards for phylogenetics. It fills a gap in the current phylogenetics toolbox in R and will facilitate the investigation of phylogenetic results. © 2017 The Authors. Molecular Ecology Resources Published by John Wiley & Sons Ltd.

Robustness of ancestral sequence reconstruction to phylogenetic uncertainty.

Science.gov (United States)

Hanson-Smith, Victor; Kolaczkowski, Bryan; Thornton, Joseph W

2010-09-01

Ancestral sequence reconstruction (ASR) is widely used to formulate and test hypotheses about the sequences, functions, and structures of ancient genes. Ancestral sequences are usually inferred from an alignment of extant sequences using a maximum likelihood (ML) phylogenetic algorithm, which calculates the most likely ancestral sequence assuming a probabilistic model of sequence evolution and a specific phylogeny--typically the tree with the ML. The true phylogeny is seldom known with certainty, however. ML methods ignore this uncertainty, whereas Bayesian methods incorporate it by integrating the likelihood of each ancestral state over a distribution of possible trees. It is not known whether Bayesian approaches to phylogenetic uncertainty improve the accuracy of inferred ancestral sequences. Here, we use simulation-based experiments under both simplified and empirically derived conditions to compare the accuracy of ASR carried out using ML and Bayesian approaches. We show that incorporating phylogenetic uncertainty by integrating over topologies very rarely changes the inferred ancestral state and does not improve the accuracy of the reconstructed ancestral sequence. Ancestral state reconstructions are robust to uncertainty about the underlying tree because the conditions that produce phylogenetic uncertainty also make the ancestral state identical across plausible trees; conversely, the conditions under which different phylogenies yield different inferred ancestral states produce little or no ambiguity about the true phylogeny. Our results suggest that ML can produce accurate ASRs, even in the face of phylogenetic uncertainty. Using Bayesian integration to incorporate this uncertainty is neither necessary nor beneficial.

Identification of a novel mutation in a Chinese family with Nance-Horan syndrome by whole exome sequencing*

Science.gov (United States)

Hong, Nan; Chen, Yan-hua; Xie, Chen; Xu, Bai-sheng; Huang, Hui; Li, Xin; Yang, Yue-qing; Huang, Ying-ping; Deng, Jian-lian; Qi, Ming; Gu, Yang-shun

2014-01-01

Objective: Nance-Horan syndrome (NHS) is a rare X-linked disorder characterized by congenital nuclear cataracts, dental anomalies, and craniofacial dysmorphisms. Mental retardation was present in about 30% of the reported cases. The purpose of this study was to investigate the genetic and clinical features of NHS in a Chinese family. Methods: Whole exome sequencing analysis was performed on DNA from an affected male to scan for candidate mutations on the X-chromosome. Sanger sequencing was used to verify these candidate mutations in the whole family. Clinical and ophthalmological examinations were performed on all members of the family. Results: A combination of exome sequencing and Sanger sequencing revealed a nonsense mutation c.322G>T (E108X) in exon 1 of NHS gene, co-segregating with the disease in the family. The nonsense mutation led to the conversion of glutamic acid to a stop codon (E108X), resulting in truncation of the NHS protein. Multiple sequence alignments showed that codon 108, where the mutation (c.322G>T) occurred, was located within a phylogenetically conserved region. The clinical features in all affected males and female carriers are described in detail. Conclusions: We report a nonsense mutation c.322G>T (E108X) in a Chinese family with NHS. Our findings broaden the spectrum of NHS mutations and provide molecular insight into future NHS clinical genetic diagnosis. PMID:25091991

Identification of a novel mutation in a Chinese family with Nance-Horan syndrome by whole exome sequencing.

Science.gov (United States)

Hong, Nan; Chen, Yan-hua; Xie, Chen; Xu, Bai-sheng; Huang, Hui; Li, Xin; Yang, Yue-qing; Huang, Ying-ping; Deng, Jian-lian; Qi, Ming; Gu, Yang-shun

2014-08-01

Nance-Horan syndrome (NHS) is a rare X-linked disorder characterized by congenital nuclear cataracts, dental anomalies, and craniofacial dysmorphisms. Mental retardation was present in about 30% of the reported cases. The purpose of this study was to investigate the genetic and clinical features of NHS in a Chinese family. Whole exome sequencing analysis was performed on DNA from an affected male to scan for candidate mutations on the X-chromosome. Sanger sequencing was used to verify these candidate mutations in the whole family. Clinical and ophthalmological examinations were performed on all members of the family. A combination of exome sequencing and Sanger sequencing revealed a nonsense mutation c.322G>T (E108X) in exon 1 of NHS gene, co-segregating with the disease in the family. The nonsense mutation led to the conversion of glutamic acid to a stop codon (E108X), resulting in truncation of the NHS protein. Multiple sequence alignments showed that codon 108, where the mutation (c.322G>T) occurred, was located within a phylogenetically conserved region. The clinical features in all affected males and female carriers are described in detail. We report a nonsense mutation c.322G>T (E108X) in a Chinese family with NHS. Our findings broaden the spectrum of NHS mutations and provide molecular insight into future NHS clinical genetic diagnosis.

FR4-Based Electromagnetic Scanning Micromirror Integrated with Angle Sensor

Directory of Open Access Journals (Sweden)

Hongjie Lei

2018-05-01

Full Text Available This paper presents a flame retardant 4 (FR4-based electromagnetic scanning micromirror, which aims to overcome the limitations of conventional microelectromechanical systems (MEMS micromirrors for the large-aperture and low-frequency scanning applications. This micromirror is fabricated through a commercial printed circuit board (PCB technology at a low cost and with a short process cycle, before an aluminum-coated silicon mirror plate with a large aperture is bonded on the FR4 platform to provide a high surface quality. In particular, an electromagnetic angle sensor is integrated to monitor the motion of the micromirror in real time. A prototype has been assembled and tested. The results show that the micromirror can reach the optical scan angle of 11.2 ∘ with a low driving voltage of only 425 mV at resonance (361.8 Hz. At the same time, the signal of the integrated angle sensor also shows good signal-to-noise ratio, linearity and sensitivity. Finally, the reliability of the FR4 based micro-mirror has been tested. The prototype successfully passes both shock and vibration tests. Furthermore, the results of the long-term mechanical cycling test (50 million cycles suggest that the maximum variations of resonant frequency and scan angle are less than 0.3% and 6%, respectively. Therefore, this simple and robust micromirror has great potential in being useful in a number of optical microsystems, especially when large-aperture or low-frequency is required.

Integral force feedback control with input shaping: Application to piezo-based scanning systems in ECDLs

Science.gov (United States)

Zhang, Meng; Liu, Zhigang; Zhu, Yu; Bu, Mingfan; Hong, Jun

2017-07-01

In this paper, a hybrid control system is developed by integrating the closed-loop force feedback and input shaping method to overcome the problem of the hysteresis and dynamic behavior in piezo-based scanning systems and increase the scanning speed of tunable external cavity diode lasers. The flexible hinge and piezoelectric actuators are analyzed, and a dynamic model of the scanning systems is established. A force sensor and an integral controller are utilized in integral force feedback (IFF) to directly augment the damping of the piezoelectric scanning systems. Hysteresis has been effectively eliminated, but the mechanical resonance is still evident. Noticeable residual vibration occurred after the inflection points and then gradually disappeared. For the further control of mechanical resonance, based on the theory of minimum-acceleration trajectory planning, the time-domain input shaping method was developed. The turning sections of a scanning trajectory are replaced by smooth curves, while the linear sections are retained. The IFF method is combined with the input shaping method to control the non-linearity and mechanical resonance in high-speed piezo-based scanning systems. Experiments are conducted, and the results demonstrate the effectiveness of the proposed control approach.

Integral force feedback control with input shaping: Application to piezo-based scanning systems in ECDLs.

Science.gov (United States)

Zhang, Meng; Liu, Zhigang; Zhu, Yu; Bu, Mingfan; Hong, Jun

2017-07-01

In this paper, a hybrid control system is developed by integrating the closed-loop force feedback and input shaping method to overcome the problem of the hysteresis and dynamic behavior in piezo-based scanning systems and increase the scanning speed of tunable external cavity diode lasers. The flexible hinge and piezoelectric actuators are analyzed, and a dynamic model of the scanning systems is established. A force sensor and an integral controller are utilized in integral force feedback (IFF) to directly augment the damping of the piezoelectric scanning systems. Hysteresis has been effectively eliminated, but the mechanical resonance is still evident. Noticeable residual vibration occurred after the inflection points and then gradually disappeared. For the further control of mechanical resonance, based on the theory of minimum-acceleration trajectory planning, the time-domain input shaping method was developed. The turning sections of a scanning trajectory are replaced by smooth curves, while the linear sections are retained. The IFF method is combined with the input shaping method to control the non-linearity and mechanical resonance in high-speed piezo-based scanning systems. Experiments are conducted, and the results demonstrate the effectiveness of the proposed control approach.

An integrative and applicable phylogenetic footprinting framework for cis-regulatory motifs identification in prokaryotic genomes.

Science.gov (United States)

Liu, Bingqiang; Zhang, Hanyuan; Zhou, Chuan; Li, Guojun; Fennell, Anne; Wang, Guanghui; Kang, Yu; Liu, Qi; Ma, Qin

2016-08-09

Phylogenetic footprinting is an important computational technique for identifying cis-regulatory motifs in orthologous regulatory regions from multiple genomes, as motifs tend to evolve slower than their surrounding non-functional sequences. Its application, however, has several difficulties for optimizing the selection of orthologous data and reducing the false positives in motif prediction. Here we present an integrative phylogenetic footprinting framework for accurate motif predictions in prokaryotic genomes (MP(3)). The framework includes a new orthologous data preparation procedure, an additional promoter scoring and pruning method and an integration of six existing motif finding algorithms as basic motif search engines. Specifically, we collected orthologous genes from available prokaryotic genomes and built the orthologous regulatory regions based on sequence similarity of promoter regions. This procedure made full use of the large-scale genomic data and taxonomy information and filtered out the promoters with limited contribution to produce a high quality orthologous promoter set. The promoter scoring and pruning is implemented through motif voting by a set of complementary predicting tools that mine as many motif candidates as possible and simultaneously eliminate the effect of random noise. We have applied the framework to Escherichia coli k12 genome and evaluated the prediction performance through comparison with seven existing programs. This evaluation was systematically carried out at the nucleotide and binding site level, and the results showed that MP(3) consistently outperformed other popular motif finding tools. We have integrated MP(3) into our motif identification and analysis server DMINDA, allowing users to efficiently identify and analyze motifs in 2,072 completely sequenced prokaryotic genomes. The performance evaluation indicated that MP(3) is effective for predicting regulatory motifs in prokaryotic genomes. Its application may enhance

Phylogenetic diversity and biodiversity indices on phylogenetic networks.

Science.gov (United States)

Wicke, Kristina; Fischer, Mareike

2018-04-01

In biodiversity conservation it is often necessary to prioritize the species to conserve. Existing approaches to prioritization, e.g. the Fair Proportion Index and the Shapley Value, are based on phylogenetic trees and rank species according to their contribution to overall phylogenetic diversity. However, in many cases evolution is not treelike and thus, phylogenetic networks have been developed as a generalization of phylogenetic trees, allowing for the representation of non-treelike evolutionary events, such as hybridization. Here, we extend the concepts of phylogenetic diversity and phylogenetic diversity indices from phylogenetic trees to phylogenetic networks. On the one hand, we consider the treelike content of a phylogenetic network, e.g. the (multi)set of phylogenetic trees displayed by a network and the so-called lowest stable ancestor tree associated with it. On the other hand, we derive the phylogenetic diversity of subsets of taxa and biodiversity indices directly from the internal structure of the network. We consider both approaches that are independent of so-called inheritance probabilities as well as approaches that explicitly incorporate these probabilities. Furthermore, we introduce our software package NetDiversity, which is implemented in Perl and allows for the calculation of all generalized measures of phylogenetic diversity and generalized phylogenetic diversity indices established in this note that are independent of inheritance probabilities. We apply our methods to a phylogenetic network representing the evolutionary relationships among swordtails and platyfishes (Xiphophorus: Poeciliidae), a group of species characterized by widespread hybridization. Copyright © 2018 Elsevier Inc. All rights reserved.

Open Reading Frame Phylogenetic Analysis on the Cloud

Directory of Open Access Journals (Sweden)

Che-Lun Hung

2013-01-01

Full Text Available Phylogenetic analysis has become essential in researching the evolutionary relationships between viruses. These relationships are depicted on phylogenetic trees, in which viruses are grouped based on sequence similarity. Viral evolutionary relationships are identified from open reading frames rather than from complete sequences. Recently, cloud computing has become popular for developing internet-based bioinformatics tools. Biocloud is an efficient, scalable, and robust bioinformatics computing service. In this paper, we propose a cloud-based open reading frame phylogenetic analysis service. The proposed service integrates the Hadoop framework, virtualization technology, and phylogenetic analysis methods to provide a high-availability, large-scale bioservice. In a case study, we analyze the phylogenetic relationships among Norovirus. Evolutionary relationships are elucidated by aligning different open reading frame sequences. The proposed platform correctly identifies the evolutionary relationships between members of Norovirus.

Deciphering the recent phylogenetic expansion of the originally deeply rooted Mycobacterium tuberculosis lineage 7.

Science.gov (United States)

Yimer, Solomon A; Namouchi, Amine; Zegeye, Ephrem Debebe; Holm-Hansen, Carol; Norheim, Gunnstein; Abebe, Markos; Aseffa, Abraham; Tønjum, Tone

2016-06-30

A deeply rooted phylogenetic lineage of Mycobacterium tuberculosis (M. tuberculosis) termed lineage 7 was discovered in Ethiopia. Whole genome sequencing of 30 lineage 7 strains from patients in Ethiopia was performed. Intra-lineage genome variation was defined and unique characteristics identified with a focus on genes involved in DNA repair, recombination and replication (3R genes). More than 800 mutations specific to M. tuberculosis lineage 7 strains were identified. The proportion of non-synonymous single nucleotide polymorphisms (nsSNPs) in 3R genes was higher after the recent expansion of M. tuberculosis lineage 7 strain started. The proportion of nsSNPs in genes involved in inorganic ion transport and metabolism was significantly higher before the expansion began. A total of 22346 bp deletions were observed. Lineage 7 strains also exhibited a high number of mutations in genes involved in carbohydrate transport and metabolism, transcription, energy production and conversion. We have identified unique genomic signatures of the lineage 7 strains. The high frequency of nsSNP in 3R genes after the phylogenetic expansion may have contributed to recent variability and adaptation. The abundance of mutations in genes involved in inorganic ion transport and metabolism before the expansion period may indicate an adaptive response of lineage 7 strains to enable survival, potentially under environmental stress exposure. As lineage 7 strains originally were phylogenetically deeply rooted, this may indicate fundamental adaptive genomic pathways affecting the fitness of M. tuberculosis as a species.

How does cognition evolve? Phylogenetic comparative psychology

Science.gov (United States)

Matthews, Luke J.; Hare, Brian A.; Nunn, Charles L.; Anderson, Rindy C.; Aureli, Filippo; Brannon, Elizabeth M.; Call, Josep; Drea, Christine M.; Emery, Nathan J.; Haun, Daniel B. M.; Herrmann, Esther; Jacobs, Lucia F.; Platt, Michael L.; Rosati, Alexandra G.; Sandel, Aaron A.; Schroepfer, Kara K.; Seed, Amanda M.; Tan, Jingzhi; van Schaik, Carel P.; Wobber, Victoria

2014-01-01

Now more than ever animal studies have the potential to test hypotheses regarding how cognition evolves. Comparative psychologists have developed new techniques to probe the cognitive mechanisms underlying animal behavior, and they have become increasingly skillful at adapting methodologies to test multiple species. Meanwhile, evolutionary biologists have generated quantitative approaches to investigate the phylogenetic distribution and function of phenotypic traits, including cognition. In particular, phylogenetic methods can quantitatively (1) test whether specific cognitive abilities are correlated with life history (e.g., lifespan), morphology (e.g., brain size), or socio-ecological variables (e.g., social system), (2) measure how strongly phylogenetic relatedness predicts the distribution of cognitive skills across species, and (3) estimate the ancestral state of a given cognitive trait using measures of cognitive performance from extant species. Phylogenetic methods can also be used to guide the selection of species comparisons that offer the strongest tests of a priori predictions of cognitive evolutionary hypotheses (i.e., phylogenetic targeting). Here, we explain how an integration of comparative psychology and evolutionary biology will answer a host of questions regarding the phylogenetic distribution and history of cognitive traits, as well as the evolutionary processes that drove their evolution. PMID:21927850

How does cognition evolve? Phylogenetic comparative psychology.

Science.gov (United States)

MacLean, Evan L; Matthews, Luke J; Hare, Brian A; Nunn, Charles L; Anderson, Rindy C; Aureli, Filippo; Brannon, Elizabeth M; Call, Josep; Drea, Christine M; Emery, Nathan J; Haun, Daniel B M; Herrmann, Esther; Jacobs, Lucia F; Platt, Michael L; Rosati, Alexandra G; Sandel, Aaron A; Schroepfer, Kara K; Seed, Amanda M; Tan, Jingzhi; van Schaik, Carel P; Wobber, Victoria

2012-03-01

Now more than ever animal studies have the potential to test hypotheses regarding how cognition evolves. Comparative psychologists have developed new techniques to probe the cognitive mechanisms underlying animal behavior, and they have become increasingly skillful at adapting methodologies to test multiple species. Meanwhile, evolutionary biologists have generated quantitative approaches to investigate the phylogenetic distribution and function of phenotypic traits, including cognition. In particular, phylogenetic methods can quantitatively (1) test whether specific cognitive abilities are correlated with life history (e.g., lifespan), morphology (e.g., brain size), or socio-ecological variables (e.g., social system), (2) measure how strongly phylogenetic relatedness predicts the distribution of cognitive skills across species, and (3) estimate the ancestral state of a given cognitive trait using measures of cognitive performance from extant species. Phylogenetic methods can also be used to guide the selection of species comparisons that offer the strongest tests of a priori predictions of cognitive evolutionary hypotheses (i.e., phylogenetic targeting). Here, we explain how an integration of comparative psychology and evolutionary biology will answer a host of questions regarding the phylogenetic distribution and history of cognitive traits, as well as the evolutionary processes that drove their evolution.

An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers.

Science.gov (United States)

Blein, Sophie; Bardel, Claire; Danjean, Vincent; McGuffog, Lesley; Healey, Sue; Barrowdale, Daniel; Lee, Andrew; Dennis, Joe; Kuchenbaecker, Karoline B; Soucy, Penny; Terry, Mary Beth; Chung, Wendy K; Goldgar, David E; Buys, Saundra S; Janavicius, Ramunas; Tihomirova, Laima; Tung, Nadine; Dorfling, Cecilia M; van Rensburg, Elizabeth J; Neuhausen, Susan L; Ding, Yuan Chun; Gerdes, Anne-Marie; Ejlertsen, Bent; Nielsen, Finn C; Hansen, Thomas Vo; Osorio, Ana; Benitez, Javier; Conejero, Raquel Andrés; Segota, Ena; Weitzel, Jeffrey N; Thelander, Margo; Peterlongo, Paolo; Radice, Paolo; Pensotti, Valeria; Dolcetti, Riccardo; Bonanni, Bernardo; Peissel, Bernard; Zaffaroni, Daniela; Scuvera, Giulietta; Manoukian, Siranoush; Varesco, Liliana; Capone, Gabriele L; Papi, Laura; Ottini, Laura; Yannoukakos, Drakoulis; Konstantopoulou, Irene; Garber, Judy; Hamann, Ute; Donaldson, Alan; Brady, Angela; Brewer, Carole; Foo, Claire; Evans, D Gareth; Frost, Debra; Eccles, Diana; Douglas, Fiona; Cook, Jackie; Adlard, Julian; Barwell, Julian; Walker, Lisa; Izatt, Louise; Side, Lucy E; Kennedy, M John; Tischkowitz, Marc; Rogers, Mark T; Porteous, Mary E; Morrison, Patrick J; Platte, Radka; Eeles, Ros; Davidson, Rosemarie; Hodgson, Shirley; Cole, Trevor; Godwin, Andrew K; Isaacs, Claudine; Claes, Kathleen; De Leeneer, Kim; Meindl, Alfons; Gehrig, Andrea; Wappenschmidt, Barbara; Sutter, Christian; Engel, Christoph; Niederacher, Dieter; Steinemann, Doris; Plendl, Hansjoerg; Kast, Karin; Rhiem, Kerstin; Ditsch, Nina; Arnold, Norbert; Varon-Mateeva, Raymonda; Schmutzler, Rita K; Preisler-Adams, Sabine; Markov, Nadja Bogdanova; Wang-Gohrke, Shan; de Pauw, Antoine; Lefol, Cédrick; Lasset, Christine; Leroux, Dominique; Rouleau, Etienne; Damiola, Francesca; Dreyfus, Hélène; Barjhoux, Laure; Golmard, Lisa; Uhrhammer, Nancy; Bonadona, Valérie; Sornin, Valérie; Bignon, Yves-Jean; Carter, Jonathan; Van Le, Linda; Piedmonte, Marion; DiSilvestro, Paul A; de la Hoya, Miguel; Caldes, Trinidad; Nevanlinna, Heli; Aittomäki, Kristiina; Jager, Agnes; van den Ouweland, Ans Mw; Kets, Carolien M; Aalfs, Cora M; van Leeuwen, Flora E; Hogervorst, Frans Bl; Meijers-Heijboer, Hanne Ej; Oosterwijk, Jan C; van Roozendaal, Kees Ep; Rookus, Matti A; Devilee, Peter; van der Luijt, Rob B; Olah, Edith; Diez, Orland; Teulé, Alex; Lazaro, Conxi; Blanco, Ignacio; Del Valle, Jesús; Jakubowska, Anna; Sukiennicki, Grzegorz; Gronwald, Jacek; Lubinski, Jan; Durda, Katarzyna; Jaworska-Bieniek, Katarzyna; Agnarsson, Bjarni A; Maugard, Christine; Amadori, Alberto; Montagna, Marco; Teixeira, Manuel R; Spurdle, Amanda B; Foulkes, William; Olswold, Curtis; Lindor, Noralane M; Pankratz, Vernon S; Szabo, Csilla I; Lincoln, Anne; Jacobs, Lauren; Corines, Marina; Robson, Mark; Vijai, Joseph; Berger, Andreas; Fink-Retter, Anneliese; Singer, Christian F; Rappaport, Christine; Kaulich, Daphne Geschwantler; Pfeiler, Georg; Tea, Muy-Kheng; Greene, Mark H; Mai, Phuong L; Rennert, Gad; Imyanitov, Evgeny N; Mulligan, Anna Marie; Glendon, Gord; Andrulis, Irene L; Tchatchou, Sandrine; Toland, Amanda Ewart; Pedersen, Inge Sokilde; Thomassen, Mads; Kruse, Torben A; Jensen, Uffe Birk; Caligo, Maria A; Friedman, Eitan; Zidan, Jamal; Laitman, Yael; Lindblom, Annika; Melin, Beatrice; Arver, Brita; Loman, Niklas; Rosenquist, Richard; Olopade, Olufunmilayo I; Nussbaum, Robert L; Ramus, Susan J; Nathanson, Katherine L; Domchek, Susan M; Rebbeck, Timothy R; Arun, Banu K; Mitchell, Gillian; Karlan, Beth Y; Lester, Jenny; Orsulic, Sandra; Stoppa-Lyonnet, Dominique; Thomas, Gilles; Simard, Jacques; Couch, Fergus J; Offit, Kenneth; Easton, Douglas F; Chenevix-Trench, Georgia; Antoniou, Antonis C; Mazoyer, Sylvie; Phelan, Catherine M; Sinilnikova, Olga M; Cox, David G

2015-04-25

Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.

INS/GPS/LiDAR Integrated Navigation System for Urban and Indoor Environments Using Hybrid Scan Matching Algorithm.

Science.gov (United States)

Gao, Yanbin; Liu, Shifei; Atia, Mohamed M; Noureldin, Aboelmagd

2015-09-15

This paper takes advantage of the complementary characteristics of Global Positioning System (GPS) and Light Detection and Ranging (LiDAR) to provide periodic corrections to Inertial Navigation System (INS) alternatively in different environmental conditions. In open sky, where GPS signals are available and LiDAR measurements are sparse, GPS is integrated with INS. Meanwhile, in confined outdoor environments and indoors, where GPS is unreliable or unavailable and LiDAR measurements are rich, LiDAR replaces GPS to integrate with INS. This paper also proposes an innovative hybrid scan matching algorithm that combines the feature-based scan matching method and Iterative Closest Point (ICP) based scan matching method. The algorithm can work and transit between two modes depending on the number of matched line features over two scans, thus achieving efficiency and robustness concurrently. Two integration schemes of INS and LiDAR with hybrid scan matching algorithm are implemented and compared. Real experiments are performed on an Unmanned Ground Vehicle (UGV) for both outdoor and indoor environments. Experimental results show that the multi-sensor integrated system can remain sub-meter navigation accuracy during the whole trajectory.

Interpreting the universal phylogenetic tree

Science.gov (United States)

Woese, C. R.

2000-01-01

The universal phylogenetic tree not only spans all extant life, but its root and earliest branchings represent stages in the evolutionary process before modern cell types had come into being. The evolution of the cell is an interplay between vertically derived and horizontally acquired variation. Primitive cellular entities were necessarily simpler and more modular in design than are modern cells. Consequently, horizontal gene transfer early on was pervasive, dominating the evolutionary dynamic. The root of the universal phylogenetic tree represents the first stage in cellular evolution when the evolving cell became sufficiently integrated and stable to the erosive effects of horizontal gene transfer that true organismal lineages could exist.

Integration of digital dental casts in cone-beam computed tomography scans

NARCIS (Netherlands)

Rangel, F.A.; Maal, T.J.J.; Berge, S.J.; Kuijpers-Jagtman, A.M.

2012-01-01

Cone-beam computed tomography (CBCT) is widely used in maxillofacial surgery. The CBCT image of the dental arches, however, is of insufficient quality to use in digital planning of orthognathic surgery. Several authors have described methods to integrate digital dental casts into CBCT scans, but all

Predicting rates of interspecific interaction from phylogenetic trees.

Science.gov (United States)

Nuismer, Scott L; Harmon, Luke J

2015-01-01

Integrating phylogenetic information can potentially improve our ability to explain species' traits, patterns of community assembly, the network structure of communities, and ecosystem function. In this study, we use mathematical models to explore the ecological and evolutionary factors that modulate the explanatory power of phylogenetic information for communities of species that interact within a single trophic level. We find that phylogenetic relationships among species can influence trait evolution and rates of interaction among species, but only under particular models of species interaction. For example, when interactions within communities are mediated by a mechanism of phenotype matching, phylogenetic trees make specific predictions about trait evolution and rates of interaction. In contrast, if interactions within a community depend on a mechanism of phenotype differences, phylogenetic information has little, if any, predictive power for trait evolution and interaction rate. Together, these results make clear and testable predictions for when and how evolutionary history is expected to influence contemporary rates of species interaction. © 2014 John Wiley & Sons Ltd/CNRS.

Phylogenetic influences on leaf trait integration in Pelargonium (Geraniaceae): convergence, divergence, and historical adaptation to a rapidly changing climate.

Science.gov (United States)

Jones, Cynthia S; Martínez-Cabrera, Hugo I; Nicotra, Adrienne B; Mocko, Kerri; Marais, Elizabeth M; Schlichting, Carl D

2013-07-01

Trait integration may improve prediction of species and lineage responses to future climate change more than individual traits alone, particularly when analyses incorporate effects of phylogenetic relationships. The South African genus Pelargonium contains divergent major clades that have radiated along the same seasonal aridity gradient, presenting the opportunity to ask whether patterns of evolution in mean leaf trait values are achieved through the same set of coordinated changes among traits in each clade. Seven leaf traits were measured on field-collected leaves from one-third of the species (98) of the genus. Trait relationships were examined using phylogenetic regression within major clades. Disparity analysis determined whether the course of trait evolution paralleled historical climate change events. Divergence in mean trait values between sister clades A1 and A2 was consistent with expectations for leaves differing in longevity, despite strong similarity between clades in trait interactions. No traits in either clade exhibited significant relationships with multivariate climate axes, with one exception. Species in clades C and A2 included in this study occupied similar environments. These clades had similar values of individual trait means, except for δ(13)C, but they exhibited distinctive patterns of trait integration. Differing present-day patterns of trait integration are consistent with interpretations of adaptive responses to the prevailing climate at the time of each clade's origin. These differing patterns of integration are likely to exert strong effects on clade-level responses to future climate change in the winter rainfall region of South Africa.

Unrealistic phylogenetic trees may improve phylogenetic footprinting.

Science.gov (United States)

Nettling, Martin; Treutler, Hendrik; Cerquides, Jesus; Grosse, Ivo

2017-06-01

The computational investigation of DNA binding motifs from binding sites is one of the classic tasks in bioinformatics and a prerequisite for understanding gene regulation as a whole. Due to the development of sequencing technologies and the increasing number of available genomes, approaches based on phylogenetic footprinting become increasingly attractive. Phylogenetic footprinting requires phylogenetic trees with attached substitution probabilities for quantifying the evolution of binding sites, but these trees and substitution probabilities are typically not known and cannot be estimated easily. Here, we investigate the influence of phylogenetic trees with different substitution probabilities on the classification performance of phylogenetic footprinting using synthetic and real data. For synthetic data we find that the classification performance is highest when the substitution probability used for phylogenetic footprinting is similar to that used for data generation. For real data, however, we typically find that the classification performance of phylogenetic footprinting surprisingly increases with increasing substitution probabilities and is often highest for unrealistically high substitution probabilities close to one. This finding suggests that choosing realistic model assumptions might not always yield optimal predictions in general and that choosing unrealistically high substitution probabilities close to one might actually improve the classification performance of phylogenetic footprinting. The proposed PF is implemented in JAVA and can be downloaded from https://github.com/mgledi/PhyFoo. : martin.nettling@informatik.uni-halle.de. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press.

Quantification of sequence exchange events between PMS2 and PMS2CL provides a basis for improved mutation scanning of Lynch syndrome patients.

Science.gov (United States)

van der Klift, Heleen M; Tops, Carli M J; Bik, Elsa C; Boogaard, Merel W; Borgstein, Anne-Marijke; Hansson, Kerstin B M; Ausems, Margreet G E M; Gomez Garcia, Encarna; Green, Andrew; Hes, Frederik J; Izatt, Louise; van Hest, Liselotte P; Alonso, Angel M; Vriends, Annette H J T; Wagner, Anja; van Zelst-Stams, Wendy A G; Vasen, Hans F A; Morreau, Hans; Devilee, Peter; Wijnen, Juul T

2010-05-01

Heterozygous mutations in PMS2 are involved in Lynch syndrome, whereas biallelic mutations are found in Constitutional mismatch repair-deficiency syndrome patients. Mutation detection is complicated by the occurrence of sequence exchange events between the duplicated regions of PMS2 and PMS2CL. We investigated the frequency of such events with a nonspecific polymerase chain reaction (PCR) strategy, co-amplifying both PMS2 and PMS2CL sequences. This allowed us to score ratios between gene and pseudogene-specific nucleotides at 29 PSV sites from exon 11 to the end of the gene. We found sequence transfer at all investigated PSVs from intron 12 to the 3' end of the gene in 4 to 52% of DNA samples. Overall, sequence exchange between PMS2 and PMS2CL was observed in 69% (83/120) of individuals. We demonstrate that mutation scanning with PMS2-specific PCR primers and MLPA probes, designed on PSVs, in the 3' duplicated region is unreliable, and present an RNA-based mutation detection strategy to improve reliability. Using this strategy, we found 19 different putative pathogenic PMS2 mutations. Four of these (21%) are lying in the region with frequent sequence transfer and are missed or called incorrectly as homozygous with several PSV-based mutation detection methods. (c) 2010 Wiley-Liss, Inc.

Mobilizing and integrating big data in studies of spatial and phylogenetic patterns of biodiversity

Directory of Open Access Journals (Sweden)

Douglas E. Soltis

2016-12-01

Full Text Available The current global challenges that threaten biodiversity are immense and rapidly growing. These biodiversity challenges demand approaches that meld bioinformatics, large-scale phylogeny reconstruction, use of digitized specimen data, and complex post-tree analyses (e.g. niche modeling, niche diversification, and other ecological analyses. Recent developments in phylogenetics coupled with emerging cyberinfrastructure and new data sources provide unparalleled opportunities for mobilizing and integrating massive amounts of biological data, driving the discovery of complex patterns and new hypotheses for further study. These developments are not trivial in that biodiversity data on the global scale now being collected and analyzed are inherently complex. The ongoing integration and maturation of biodiversity tools discussed here is transforming biodiversity science, enabling what we broadly term “next-generation” investigations in systematics, ecology, and evolution (i.e., “biodiversity science”. New training that integrates domain knowledge in biodiversity and data science skills is also needed to accelerate research in these areas. Integrative biodiversity science is crucial to the future of global biodiversity. We cannot simply react to continued threats to biodiversity, but via the use of an integrative, multifaceted, big data approach, researchers can now make biodiversity projections to provide crucial data not only for scientists, but also for the public, land managers, policy makers, urban planners, and agriculture.

Phylogenetic trees

OpenAIRE

Baños, Hector; Bushek, Nathaniel; Davidson, Ruth; Gross, Elizabeth; Harris, Pamela E.; Krone, Robert; Long, Colby; Stewart, Allen; Walker, Robert

2016-01-01

We introduce the package PhylogeneticTrees for Macaulay2 which allows users to compute phylogenetic invariants for group-based tree models. We provide some background information on phylogenetic algebraic geometry and show how the package PhylogeneticTrees can be used to calculate a generating set for a phylogenetic ideal as well as a lower bound for its dimension. Finally, we show how methods within the package can be used to compute a generating set for the join of any two ideals.

Construction of a phylogenetic tree of photosynthetic prokaryotes based on average similarities of whole genome sequences.

Directory of Open Access Journals (Sweden)

Soichirou Satoh

Full Text Available Phylogenetic trees have been constructed for a wide range of organisms using gene sequence information, especially through the identification of orthologous genes that have been vertically inherited. The number of available complete genome sequences is rapidly increasing, and many tools for construction of genome trees based on whole genome sequences have been proposed. However, development of a reasonable method of using complete genome sequences for construction of phylogenetic trees has not been established. We have developed a method for construction of phylogenetic trees based on the average sequence similarities of whole genome sequences. We used this method to examine the phylogeny of 115 photosynthetic prokaryotes, i.e., cyanobacteria, Chlorobi, proteobacteria, Chloroflexi, Firmicutes and nonphotosynthetic organisms including Archaea. Although the bootstrap values for the branching order of phyla were low, probably due to lateral gene transfer and saturated mutation, the obtained tree was largely consistent with the previously reported phylogenetic trees, indicating that this method is a robust alternative to traditional phylogenetic methods.

Evolution of microgastropods (Ellobioidea, Carychiidae): integrating taxonomic, phylogenetic and evolutionary hypotheses

Science.gov (United States)

2013-01-01

Background Current biodiversity patterns are considered largely the result of past climatic and tectonic changes. In an integrative approach, we combine taxonomic and phylogenetic hypotheses to analyze temporal and geographic diversification of epigean (Carychium) and subterranean (Zospeum) evolutionary lineages in Carychiidae (Eupulmonata, Ellobioidea). We explicitly test three hypotheses: 1) morphospecies encompass unrecognized evolutionary lineages, 2) limited dispersal results in a close genetic relationship of geographical proximally distributed taxa and 3) major climatic and tectonic events had an impact on lineage diversification within Carychiidae. Results Initial morphospecies assignments were investigated by different molecular delimitation approaches (threshold, ABGD, GMYC and SP). Despite a conservative delimitation strategy, carychiid morphospecies comprise a great number of unrecognized evolutionary lineages. We attribute this phenomenon to historic underestimation of morphological stasis and phenotypic variability amongst lineages. The first molecular phylogenetic hypothesis for the Carychiidae (based on COI, 16S and H3) reveals Carychium and Zospeum to be reciprocally monophyletic. Geographical proximally distributed lineages are often closely related. The temporal diversification of Carychiidae is best described by a constant rate model of diversification. The evolution of Carychiidae is characterized by relatively few (long distance) colonization events. We find support for an Asian origin of Carychium. Zospeum may have arrived in Europe before extant members of Carychium. Distantly related Carychium clades inhabit a wide spectrum of the available bioclimatic niche and demonstrate considerable niche overlap. Conclusions Carychiid taxonomy is in dire need of revision. An inferred wide distribution and variable phenotype suggest underestimated diversity in Zospeum. Several Carychium morphospecies are results of past taxonomic lumping. By collecting

TREEFINDER: a powerful graphical analysis environment for molecular phylogenetics

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von Haeseler Arndt

2004-06-01

Full Text Available Abstract Background Most analysis programs for inferring molecular phylogenies are difficult to use, in particular for researchers with little programming experience. Results TREEFINDER is an easy-to-use integrative platform-independent analysis environment for molecular phylogenetics. In this paper the main features of TREEFINDER (version of April 2004 are described. TREEFINDER is written in ANSI C and Java and implements powerful statistical approaches for inferring gene tree and related analyzes. In addition, it provides a user-friendly graphical interface and a phylogenetic programming language. Conclusions TREEFINDER is a versatile framework for analyzing phylogenetic data across different platforms that is suited both for exploratory as well as advanced studies.

YBYRÁ facilitates comparison of large phylogenetic trees.

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Machado, Denis Jacob

2015-07-01

The number and size of tree topologies that are being compared by phylogenetic systematists is increasing due to technological advancements in high-throughput DNA sequencing. However, we still lack tools to facilitate comparison among phylogenetic trees with a large number of terminals. The "YBYRÁ" project integrates software solutions for data analysis in phylogenetics. It comprises tools for (1) topological distance calculation based on the number of shared splits or clades, (2) sensitivity analysis and automatic generation of sensitivity plots and (3) clade diagnoses based on different categories of synapomorphies. YBYRÁ also provides (4) an original framework to facilitate the search for potential rogue taxa based on how much they affect average matching split distances (using MSdist). YBYRÁ facilitates comparison of large phylogenetic trees and outperforms competing software in terms of usability and time efficiency, specially for large data sets. The programs that comprises this toolkit are written in Python, hence they do not require installation and have minimum dependencies. The entire project is available under an open-source licence at http://www.ib.usp.br/grant/anfibios/researchSoftware.html .

Integration of published information into a resistance-associated mutation database for Mycobacterium tuberculosis.

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Salamon, Hugh; Yamaguchi, Ken D; Cirillo, Daniela M; Miotto, Paolo; Schito, Marco; Posey, James; Starks, Angela M; Niemann, Stefan; Alland, David; Hanna, Debra; Aviles, Enrique; Perkins, Mark D; Dolinger, David L

2015-04-01

Tuberculosis remains a major global public health challenge. Although incidence is decreasing, the proportion of drug-resistant cases is increasing. Technical and operational complexities prevent Mycobacterium tuberculosis drug susceptibility phenotyping in the vast majority of new and retreatment cases. The advent of molecular technologies provides an opportunity to obtain results rapidly as compared to phenotypic culture. However, correlations between genetic mutations and resistance to multiple drugs have not been systematically evaluated. Molecular testing of M. tuberculosis sampled from a typical patient continues to provide a partial picture of drug resistance. A database of phenotypic and genotypic testing results, especially where prospectively collected, could document statistically significant associations and may reveal new, predictive molecular patterns. We examine the feasibility of integrating existing molecular and phenotypic drug susceptibility data to identify associations observed across multiple studies and demonstrate potential for well-integrated M. tuberculosis mutation data to reveal actionable findings. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

AlaScan: A Graphical User Interface for Alanine Scanning Free-Energy Calculations.

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Ramadoss, Vijayaraj; Dehez, François; Chipot, Christophe

2016-06-27

Computation of the free-energy changes that underlie molecular recognition and association has gained significant importance due to its considerable potential in drug discovery. The massive increase of computational power in recent years substantiates the application of more accurate theoretical methods for the calculation of binding free energies. The impact of such advances is the application of parent approaches, like computational alanine scanning, to investigate in silico the effect of amino-acid replacement in protein-ligand and protein-protein complexes, or probe the thermostability of individual proteins. Because human effort represents a significant cost that precludes the routine use of this form of free-energy calculations, minimizing manual intervention constitutes a stringent prerequisite for any such systematic computation. With this objective in mind, we propose a new plug-in, referred to as AlaScan, developed within the popular visualization program VMD to automate the major steps in alanine-scanning calculations, employing free-energy perturbation as implemented in the widely used molecular dynamics code NAMD. The AlaScan plug-in can be utilized upstream, to prepare input files for selected alanine mutations. It can also be utilized downstream to perform the analysis of different alanine-scanning calculations and to report the free-energy estimates in a user-friendly graphical user interface, allowing favorable mutations to be identified at a glance. The plug-in also assists the end-user in assessing the reliability of the calculation through rapid visual inspection.

Incompletely resolved phylogenetic trees inflate estimates of phylogenetic conservatism.

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Davies, T Jonathan; Kraft, Nathan J B; Salamin, Nicolas; Wolkovich, Elizabeth M

2012-02-01

The tendency for more closely related species to share similar traits and ecological strategies can be explained by their longer shared evolutionary histories and represents phylogenetic conservatism. How strongly species traits co-vary with phylogeny can significantly impact how we analyze cross-species data and can influence our interpretation of assembly rules in the rapidly expanding field of community phylogenetics. Phylogenetic conservatism is typically quantified by analyzing the distribution of species values on the phylogenetic tree that connects them. Many phylogenetic approaches, however, assume a completely sampled phylogeny: while we have good estimates of deeper phylogenetic relationships for many species-rich groups, such as birds and flowering plants, we often lack information on more recent interspecific relationships (i.e., within a genus). A common solution has been to represent these relationships as polytomies on trees using taxonomy as a guide. Here we show that such trees can dramatically inflate estimates of phylogenetic conservatism quantified using S. P. Blomberg et al.'s K statistic. Using simulations, we show that even randomly generated traits can appear to be phylogenetically conserved on poorly resolved trees. We provide a simple rarefaction-based solution that can reliably retrieve unbiased estimates of K, and we illustrate our method using data on first flowering times from Thoreau's woods (Concord, Massachusetts, USA).

Darwinism for the Genomic Age: Connecting Mutation to Diversification.

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Hua, Xia; Bromham, Lindell

2017-01-01

A growing body of evidence suggests that rates of diversification of biological lineages are correlated with differences in genome-wide mutation rate. Given that most research into differential patterns of diversification rate have focused on species traits or ecological parameters, a connection to the biochemical processes of genome change is an unexpected observation. While the empirical evidence for a significant association between mutation rate and diversification rate is mounting, there has been less effort in explaining the factors that mediate this connection between genetic change and species richness. Here we draw together empirical studies and theoretical concepts that may help to build links in the explanatory chain that connects mutation to diversification. First we consider the way that mutation rates vary between species. We then explore how differences in mutation rates have flow-through effects to the rate at which populations acquire substitutions, which in turn influences the speed at which populations become reproductively isolated from each other due to the acquisition of genomic incompatibilities. Since diversification rate is commonly measured from phylogenetic analyses, we propose a conceptual approach for relating events of reproductive isolation to bifurcations on molecular phylogenies. As we examine each of these relationships, we consider theoretical models that might shine a light on the observed association between rate of molecular evolution and diversification rate, and critically evaluate the empirical evidence for these links, focusing on phylogenetic comparative studies. Finally, we ask whether we are getting closer to a real understanding of the way that the processes of molecular evolution connect to the observable patterns of diversification.

Registration area and accuracy when integrating laser-scanned and maxillofacial cone-beam computed tomography images.

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Sun, LiJun; Hwang, Hyeon-Shik; Lee, Kyung-Min

2018-03-01

The purpose of this study was to examine changes in registration accuracy after including occlusal surface and incisal edge areas in addition to the buccal surface when integrating laser-scanned and maxillofacial cone-beam computed tomography (CBCT) dental images. CBCT scans and maxillary dental casts were obtained from 30 patients. Three methods were used to integrate the images: R1, only the buccal and labial surfaces were used; R2, the incisal edges of the anterior teeth and the buccal and distal marginal ridges of the second molars were used; and R3, labial surfaces, including incisal edges of anterior teeth, and buccal surfaces, including buccal and distal marginal ridges of the second molars, were used. Differences between the 2 images were evaluated by color-mapping methods and average surface distances by measuring the 3-dimensional Euclidean distances between the surface points on the 2 images. The R1 method showed more discrepancies between the laser-scanned and CBCT images than did the other methods. The R2 method did not show a significant difference in registration accuracy compared with the R3 method. The results of this study indicate that accuracy when integrating laser-scanned dental images into maxillofacial CBCT images can be increased by including occlusal surface and incisal edge areas as registration areas. Copyright © 2017 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Integrative taxonomy of ciliates: Assessment of molecular phylogenetic content and morphological homology testing.

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Vďačný, Peter

2017-10-01

The very diverse and comparatively complex morphology of ciliates has given rise to numerous taxonomic concepts. However, the information content of the utilized molecular markers has seldom been explored prior to phylogenetic analyses and taxonomic decisions. Likewise, robust testing of morphological homology statements and the apomorphic nature of diagnostic characters of ciliate taxa is rarely carried out. Four phylogenetic techniques that may help address these issues are reviewed. (1) Split spectrum analysis serves to determine the exact number and quality of nucleotide positions supporting individual nodes in phylogenetic trees and to discern long-branch artifacts that cause spurious phylogenies. (2) Network analysis can depict all possible evolutionary trajectories inferable from the dataset and locate and measure the conflict between them. (3) A priori likelihood mapping tests the suitability of data for reconstruction of a well resolved tree, visualizes the tree-likeness of quartets, and assesses the support of an internal branch of a given tree topology. (4) Reconstruction of ancestral morphologies can be applied for analyzing homology and apomorphy statements without circular reasoning. Since these phylogenetic tools are rarely used, their principles and interpretation are introduced and exemplified using various groups of ciliates. Finally, environmental sequencing data are discussed in this light. Copyright © 2017 The Author. Published by Elsevier GmbH.. All rights reserved.

Phylogenetic analysis of partial RNA-polymerase blocks II and III of Rabies virus isolated from the main rabies reservoirs in Brazil.

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Carnieli, Pedro; de Novaes Oliveira, Rafael; de Oliveira Fahl, Willian; de Carvalho Ruthner Batista, Helena Beatriz; Scheffer, Karin Corrêa; Iamamoto, Keila; Castilho, Juliana Galera

2012-08-01

This study describes the results of the sequencing and analysis of segments of Blocks II and III of the RNA polymerase L gene of Rabies virus isolates from different reservoir species of Brazil. The phylogenetic relations of the virus were determined and a variety of species-specific nucleotides were found in the analyzed areas, but the majority of these mutations were found to be synonymous. However, an analysis of the putative amino acid sequences were shown to have some characteristic mutations between some reservoir species of Brazil, indicating that there was positive selection in the RNA polymerase L gene of Rabies virus. On comparing the putative viral sequences obtained from the Brazilian isolates and other Lyssavirus, it was determined that amino acid mutations occurred in low-restriction areas. This study of the L gene of Rabies virus is the first to be conducted with samples of virus isolates from Brazil, and the results obtained will help in the determination of the phylogenetic relations of the virus.

Integration of scanned document management with the anatomic pathology laboratory information system: analysis of benefits.

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Schmidt, Rodney A; Simmons, Kim; Grimm, Erin E; Middlebrooks, Michael; Changchien, Rosy

2006-11-01

Electronic document management systems (EDMSs) have the potential to improve the efficiency of anatomic pathology laboratories. We implemented a novel but simple EDMS for scanned documents as part of our laboratory information system (AP-LIS) and collected cost-benefit data with the intention of discerning the value of such a system in general and whether integration with the AP-LIS is advantageous. We found that the direct financial benefits are modest but the indirect and intangible benefits are large. Benefits of time savings and access to data particularly accrued to pathologists and residents (3.8 h/d saved for 26 pathologists and residents). Integrating the scanned document management system (SDMS) into the AP-LIS has major advantages in terms of workflow and overall simplicity. This simple, integrated SDMS is an excellent value in a practice like ours, and many of the benefits likely apply in other practice settings.

The functional importance of disease-associated mutation

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Klein Teri E

2002-09-01

Full Text Available Abstract Background For many years, scientists believed that point mutations in genes are the genetic switches for somatic and inherited diseases such as cystic fibrosis, phenylketonuria and cancer. Some of these mutations likely alter a protein's function in a manner that is deleterious, and they should occur in functionally important regions of the protein products of genes. Here we show that disease-associated mutations occur in regions of genes that are conserved, and can identify likely disease-causing mutations. Results To show this, we have determined conservation patterns for 6185 non-synonymous and heritable disease-associated mutations in 231 genes. We define a parameter, the conservation ratio, as the ratio of average negative entropy of analyzable positions with reported mutations to that of every analyzable position in the gene sequence. We found that 84.0% of the 231 genes have conservation ratios less than one. 139 genes had eleven or more analyzable mutations and 88.0% of those had conservation ratios less than one. Conclusions These results indicate that phylogenetic information is a powerful tool for the study of disease-associated mutations. Our alignments and analysis has been made available as part of the database at http://cancer.stanford.edu/mut-paper/. Within this dataset, each position is annotated with the analysis, so the most likely disease-causing mutations can be identified.

The HIVToolbox 2 web system integrates sequence, structure, function and mutation analysis.

Directory of Open Access Journals (Sweden)

David P Sargeant

Full Text Available There is enormous interest in studying HIV pathogenesis for improving the treatment of patients with HIV infection. HIV infection has become one of the best-studied systems for understanding how a virus can hijack a cell. To help facilitate discovery, we previously built HIVToolbox, a web system for visual data mining. The original HIVToolbox integrated information for HIV protein sequence, structure, functional sites, and sequence conservation. This web system has been used for almost 40,000 searches. We report improvements to HIVToolbox including new functions and workflows, data updates, and updates for ease of use. HIVToolbox2, is an improvement over HIVToolbox with new functions. HIVToolbox2 has new functionalities focused on HIV pathogenesis including drug-binding sites, drug-resistance mutations, and immune epitopes. The integrated, interactive view enables visual mining to generate hypotheses that are not readily revealed by other approaches. Most HIV proteins form multimers, and there are posttranslational modification and protein-protein interaction sites at many of these multimerization interfaces. Analysis of protease drug binding sites reveals an anatomy of drug resistance with different types of drug-resistance mutations regionally localized on the surface of protease. Some of these drug-resistance mutations have a high prevalence in specific HIV-1 M subtypes. Finally, consolidation of Tat functional sites reveals a hotspot region where there appear to be 30 interactions or posttranslational modifications. A cursory analysis with HIVToolbox2 has helped to identify several global patterns for HIV proteins. An initial analysis with this tool identifies homomultimerization of almost all HIV proteins, functional sites that overlap with multimerization sites, a global drug resistance anatomy for HIV protease, and specific distributions of some DRMs in specific HIV M subtypes. HIVToolbox2 is an open-access web application available at

HIV-1 diversity and drug-resistant mutations in infected individuals in Changchun, China.

Directory of Open Access Journals (Sweden)

Ming Yan

Full Text Available OBJECTIVES: Human immunodeficiency virus type 1 (HIV-1 infection has been detected in all provinces of China. Although epidemiological and phylogenetic studies have been conducted in many regions, such analyses are lacking from Jilin province in northeastern China. METHOD: Epidemiological and phylogenetic analyses, as well as detection of drug-resistant mutations, were conducted on 57 HIV-1 infected patients from Changchun city identified and confirmed through annual surveillance by local Centers for Disease Control in Jilin province of northeastern China in 2012. RESULTS: Sexual contact was determined to be the major pathway for HIV-1 transmission in Jilin, where hetero- and homosexual activities contributed almost equally. Phylogenetic analyses detected multiple subtypes of HIV-1 including subtype G circulating in Jilin, with multiple origins for each of them. Both subtype B and CRF01_AE were dominant, and evidence of subtype B transmitting between different high-risk groups was observed. Mutations in the viral protease at position 71 indicated the presence of a selective pressure. Several drug-resistant mutations were detected, although they were predicted with low-level resistance to antiviral treatments. CONCLUSIONS: Information from this study fills the gap in knowledge of HIV-1 transmission in Changchun city, Jilin province, China. By revealing the origin and evolutionary status of local HIV-1 strains, this work contributes to ongoing efforts in the control and prevention of AIDS.

Ghost-tree: creating hybrid-gene phylogenetic trees for diversity analyses.

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Fouquier, Jennifer; Rideout, Jai Ram; Bolyen, Evan; Chase, John; Shiffer, Arron; McDonald, Daniel; Knight, Rob; Caporaso, J Gregory; Kelley, Scott T

2016-02-24

Fungi play critical roles in many ecosystems, cause serious diseases in plants and animals, and pose significant threats to human health and structural integrity problems in built environments. While most fungal diversity remains unknown, the development of PCR primers for the internal transcribed spacer (ITS) combined with next-generation sequencing has substantially improved our ability to profile fungal microbial diversity. Although the high sequence variability in the ITS region facilitates more accurate species identification, it also makes multiple sequence alignment and phylogenetic analysis unreliable across evolutionarily distant fungi because the sequences are hard to align accurately. To address this issue, we created ghost-tree, a bioinformatics tool that integrates sequence data from two genetic markers into a single phylogenetic tree that can be used for diversity analyses. Our approach starts with a "foundation" phylogeny based on one genetic marker whose sequences can be aligned across organisms spanning divergent taxonomic groups (e.g., fungal families). Then, "extension" phylogenies are built for more closely related organisms (e.g., fungal species or strains) using a second more rapidly evolving genetic marker. These smaller phylogenies are then grafted onto the foundation tree by mapping taxonomic names such that each corresponding foundation-tree tip would branch into its new "extension tree" child. We applied ghost-tree to graft fungal extension phylogenies derived from ITS sequences onto a foundation phylogeny derived from fungal 18S sequences. Our analysis of simulated and real fungal ITS data sets found that phylogenetic distances between fungal communities computed using ghost-tree phylogenies explained significantly more variance than non-phylogenetic distances. The phylogenetic metrics also improved our ability to distinguish small differences (effect sizes) between microbial communities, though results were similar to non-phylogenetic

Phylogenetic comparative methods on phylogenetic networks with reticulations.

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Bastide, Paul; Solís-Lemus, Claudia; Kriebel, Ricardo; Sparks, K William; Ané, Cécile

2018-04-25

The goal of Phylogenetic Comparative Methods (PCMs) is to study the distribution of quantitative traits among related species. The observed traits are often seen as the result of a Brownian Motion (BM) along the branches of a phylogenetic tree. Reticulation events such as hybridization, gene flow or horizontal gene transfer, can substantially affect a species' traits, but are not modeled by a tree. Phylogenetic networks have been designed to represent reticulate evolution. As they become available for downstream analyses, new models of trait evolution are needed, applicable to networks. One natural extension of the BM is to use a weighted average model for the trait of a hybrid, at a reticulation point. We develop here an efficient recursive algorithm to compute the phylogenetic variance matrix of a trait on a network, in only one preorder traversal of the network. We then extend the standard PCM tools to this new framework, including phylogenetic regression with covariates (or phylogenetic ANOVA), ancestral trait reconstruction, and Pagel's λ test of phylogenetic signal. The trait of a hybrid is sometimes outside of the range of its two parents, for instance because of hybrid vigor or hybrid depression. These two phenomena are rather commonly observed in present-day hybrids. Transgressive evolution can be modeled as a shift in the trait value following a reticulation point. We develop a general framework to handle such shifts, and take advantage of the phylogenetic regression view of the problem to design statistical tests for ancestral transgressive evolution in the evolutionary history of a group of species. We study the power of these tests in several scenarios, and show that recent events have indeed the strongest impact on the trait distribution of present-day taxa. We apply those methods to a dataset of Xiphophorus fishes, to confirm and complete previous analysis in this group. All the methods developed here are available in the Julia package PhyloNetworks.

Mutational analyses of the core domain of Avian Leukemia and Sarcoma Viruses integrase: critical residues for concerted integration and multimerization

International Nuclear Information System (INIS)

Moreau, Karen; Faure, Claudine; Violot, Sebastien; Gouet, Patrice; Verdier, Gerard; Ronfort, Corinne

2004-01-01

During replicative cycle of retroviruses, the reverse-transcribed viral DNA is integrated into the cell DNA by the viral integrase (IN) enzyme. The central core domain of IN contains the catalytic site of the enzyme and is involved in binding viral ends and cell DNA as well as dimerization. We previously performed single amino acid substitutions in the core domain of an Avian Leukemia and Sarcoma Virus (ALSV) IN [Arch. Virol. 147 (2002) 1761]. Here, we modeled the resulting IN mutants and analyzed the ability of these mutants to mediate concerted DNA integration in an in vitro assay, and to form dimers by protein-protein cross-linking and size exclusion chromatography. The N197C mutation resulted in the inability of the mutant to perform concerted integration that was concomitant with a loss of IN dimerization. Surprisingly, mutations Q102G and A106V at the dimer interface resulted in mutants with higher efficiencies than the wild-type IN in performing two-ended concerted integration of viral DNA ends. The G139D and A195V mutants had a trend to perform one-ended DNA integration of viral ends instead of two-ended integration. More drastically, the I88L and L135G mutants preferentially mediated nonconcerted DNA integration although the proteins form dimers. Therefore, these mutations may alter the formation of IN complexes of higher molecular size than a dimer that would be required for concerted integration. This study points to the important role of core domain residues in the concerted integration of viral DNA ends as well as in the oligomerization of the enzyme

Turnover of plant lineages shapes herbivore phylogenetic beta diversity along ecological gradients.

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Pellissier, Loïc; Ndiribe, Charlotte; Dubuis, Anne; Pradervand, Jean-Nicolas; Salamin, Nicolas; Guisan, Antoine; Rasmann, Sergio

2013-05-01

Understanding drivers of biodiversity patterns is of prime importance in this era of severe environmental crisis. More diverse plant communities have been postulated to represent a larger functional trait-space, more likely to sustain a diverse assembly of herbivore species. Here, we expand this hypothesis to integrate environmental, functional and phylogenetic variation of plant communities as factors explaining the diversity of lepidopteran assemblages along elevation gradients in the Swiss Western Alps. According to expectations, we found that the association between butterflies and their host plants is highly phylogenetically structured. Multiple regression analyses showed the combined effect of climate, functional traits and phylogenetic diversity in structuring butterfly communities. Furthermore, we provide the first evidence that plant phylogenetic beta diversity is the major driver explaining butterfly phylogenetic beta diversity. Along ecological gradients, the bottom up control of herbivore diversity is thus driven by phylogenetically structured turnover of plant traits as well as environmental variables. © 2013 Blackwell Publishing Ltd/CNRS.

Evolution of the Pseudomonas aeruginosa mutational resistome in an international Cystic Fibrosis clone

DEFF Research Database (Denmark)

López-Causapé, Carla; Madsen Sommer, Lea Mette; Cabot, Gabriel

2017-01-01

) and resistome of a widespread clone (CC274), in isolates from two highly-distant countries, Australia and Spain, covering an 18-year period. The coexistence of two divergent CC274 clonal lineages was revealed, but without evident geographical barrier; phylogenetic reconstructions and mutational resistome...... for the first time that high-level aminoglycoside resistance in CF is likely driven by mutations in fusA1/fusA2, coding for elongation factor G. Altogether, our results provide valuable information for understanding the evolution of the mutational resistome of CF P. aeruginosa....

Integration of a high-NA light microscope in a scanning electron microscope.

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Zonnevylle, A C; Van Tol, R F C; Liv, N; Narvaez, A C; Effting, A P J; Kruit, P; Hoogenboom, J P

2013-10-01

We present an integrated light-electron microscope in which an inverted high-NA objective lens is positioned inside a scanning electron microscope (SEM). The SEM objective lens and the light objective lens have a common axis and focal plane, allowing high-resolution optical microscopy and scanning electron microscopy on the same area of a sample simultaneously. Components for light illumination and detection can be mounted outside the vacuum, enabling flexibility in the construction of the light microscope. The light objective lens can be positioned underneath the SEM objective lens during operation for sub-10 μm alignment of the fields of view of the light and electron microscopes. We demonstrate in situ epifluorescence microscopy in the SEM with a numerical aperture of 1.4 using vacuum-compatible immersion oil. For a 40-nm-diameter fluorescent polymer nanoparticle, an intensity profile with a FWHM of 380 nm is measured whereas the SEM performance is uncompromised. The integrated instrument may offer new possibilities for correlative light and electron microscopy in the life sciences as well as in physics and chemistry. © 2013 The Authors Journal of Microscopy © 2013 Royal Microscopical Society.

On the group theoretical background of assigning stepwise mutations onto phylogenies

NARCIS (Netherlands)

Fischer, Mareike; Klaere, Steffen; Minh Anh Thi Nguyen, [No Value; von Haeseler, Arndt

2012-01-01

Recently one step mutation matrices were introduced to model the impact of substitutions on arbitrary branches of a phylogenetic tree on an alignment site. This concept works nicely for the four-state nucleotide alphabet and provides an efficient procedure conjectured to compute the minimal number

Noninvasive computerized scanning method for the correlation between the facial soft and hard tissues for an integrated three-dimensional anthropometry and cephalometry.

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Galantucci, Luigi Maria; Percoco, Gianluca; Lavecchia, Fulvio; Di Gioia, Eliana

2013-05-01

The article describes a new methodology to scan and integrate facial soft tissue surface with dental hard tissue models in a three-dimensional (3D) virtual environment, for a novel diagnostic approach.The facial and the dental scans can be acquired using any optical scanning systems: the models are then aligned and integrated to obtain a full virtual navigable representation of the head of the patient. In this article, we report in detail and further implemented a method for integrating 3D digital cast models into a 3D facial image, to visualize the anatomic position of the dentition. This system uses several 3D technologies to scan and digitize, integrating them with traditional dentistry records. The acquisitions were mainly performed using photogrammetric scanners, suitable for clinics or hospitals, able to obtain high mesh resolution and optimal surface texture for the photorealistic rendering of the face. To increase the quality and the resolution of the photogrammetric scanning of the dental elements, the authors propose a new technique to enhance the texture of the dental surface. Three examples of the application of the proposed procedure are reported in this article, using first laser scanning and photogrammetry and then only photogrammetry. Using cheek retractors, it is possible to scan directly a great number of dental elements. The final results are good navigable 3D models that integrate facial soft tissue and dental hard tissues. The method is characterized by the complete absence of ionizing radiation, portability and simplicity, fast acquisition, easy alignment of the 3D models, and wide angle of view of the scanner. This method is completely noninvasive and can be repeated any time the physician needs new clinical records. The 3D virtual model is a precise representation both of the soft and the hard tissue scanned, and it is possible to make any dimensional measure directly in the virtual space, for a full integrated 3D anthropometry and

Towards a phylogenetic classification of reef corals: The Indo-Pacific genera Merulina, Goniastrea and Scapophyllia (Scleractinia, Merulinidae)

KAUST Repository

Huang, Danwei

2014-06-03

Recent advances in scleractinian systematics and taxonomy have been achieved through the integration of molecular and morphological data, as well as rigorous analysis using phylogenetic methods. In this study, we continue in our pursuit of a phylogenetic classification by examining the evolutionary relationships between the closely related reef coral genera Merulina, Goniastrea, Paraclavarina and Scapophyllia (Merulinidae). In particular, we address the extreme polyphyly of Favites and Goniastrea that was discovered a decade ago. We sampled 145 specimens belonging to 16 species from a wide geographic range in the Indo-Pacific, focusing especially on type localities, including the Red Sea, western Indian Ocean and central Pacific. Tree reconstructions based on both nuclear and mitochondrial markers reveal a novel lineage composed of three species previously placed in Favites and Goniastrea. Morphological analyses indicate that this clade, Paragoniastrea Huang, Benzoni & Budd, gen. n., has a unique combination of corallite and subcorallite features observable with scanning electron microscopy and thin sections. Molecular and morphological evidence furthermore indicates that the monotypic genus Paraclavarina is nested within Merulina, and the former is therefore synonymised. © 2014 Royal Swedish Academy of Sciences.

Efficient Detection of Repeating Sites to Accelerate Phylogenetic Likelihood Calculations.

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Kobert, K; Stamatakis, A; Flouri, T

2017-03-01

The phylogenetic likelihood function (PLF) is the major computational bottleneck in several applications of evolutionary biology such as phylogenetic inference, species delimitation, model selection, and divergence times estimation. Given the alignment, a tree and the evolutionary model parameters, the likelihood function computes the conditional likelihood vectors for every node of the tree. Vector entries for which all input data are identical result in redundant likelihood operations which, in turn, yield identical conditional values. Such operations can be omitted for improving run-time and, using appropriate data structures, reducing memory usage. We present a fast, novel method for identifying and omitting such redundant operations in phylogenetic likelihood calculations, and assess the performance improvement and memory savings attained by our method. Using empirical and simulated data sets, we show that a prototype implementation of our method yields up to 12-fold speedups and uses up to 78% less memory than one of the fastest and most highly tuned implementations of the PLF currently available. Our method is generic and can seamlessly be integrated into any phylogenetic likelihood implementation. [Algorithms; maximum likelihood; phylogenetic likelihood function; phylogenetics]. © The Author(s) 2016. Published by Oxford University Press, on behalf of the Society of Systematic Biologists.

Stability of transmembrane amyloid β-peptide and membrane integrity tested by molecular modeling of site-specific Aβ42 mutations.

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Chetan Poojari

Full Text Available Interactions of the amyloid β-protein (Aβ with neuronal cell membranes, leading to the disruption of membrane integrity, are considered to play a key role in the development of Alzheimer's disease. Natural mutations in Aβ42, such as the Arctic mutation (E22G have been shown to increase Aβ42 aggregation and neurotoxicity, leading to the early-onset of Alzheimer's disease. A correlation between the propensity of Aβ42 to form protofibrils and its effect on neuronal dysfunction and degeneration has been established. Using rational mutagenesis of the Aβ42 peptide it was further revealed that the aggregation of different Aβ42 mutants in lipid membranes results in a variety of polymorphic aggregates in a mutation dependent manner. The mutant peptides also have a variable ability to disrupt bilayer integrity. To further test the connection between Aβ42 mutation and peptide-membrane interactions, we perform molecular dynamics simulations of membrane-inserted Aβ42 variants (wild-type and E22G, D23G, E22G/D23G, K16M/K28M and K16M/E22G/D23G/K28M mutants as β-sheet monomers and tetramers. The effects of charged residues on transmembrane Aβ42 stability and membrane integrity are analyzed at atomistic level. We observe an increased stability for the E22G Aβ42 peptide and a decreased stability for D23G compared to wild-type Aβ42, while D23G has the largest membrane-disruptive effect. These results support the experimental observation that the altered toxicity arising from mutations in Aβ is not only a result of the altered aggregation propensity, but also originates from modified Aβ interactions with neuronal membranes.

jsPhyloSVG: a javascript library for visualizing interactive and vector-based phylogenetic trees on the web.

Science.gov (United States)

Smits, Samuel A; Ouverney, Cleber C

2010-08-18

Many software packages have been developed to address the need for generating phylogenetic trees intended for print. With an increased use of the web to disseminate scientific literature, there is a need for phylogenetic trees to be viewable across many types of devices and feature some of the interactive elements that are integral to the browsing experience. We propose a novel approach for publishing interactive phylogenetic trees. We present a javascript library, jsPhyloSVG, which facilitates constructing interactive phylogenetic trees from raw Newick or phyloXML formats directly within the browser in Scalable Vector Graphics (SVG) format. It is designed to work across all major browsers and renders an alternative format for those browsers that do not support SVG. The library provides tools for building rectangular and circular phylograms with integrated charting. Interactive features may be integrated and made to respond to events such as clicks on any element of the tree, including labels. jsPhyloSVG is an open-source solution for rendering dynamic phylogenetic trees. It is capable of generating complex and interactive phylogenetic trees across all major browsers without the need for plugins. It is novel in supporting the ability to interpret the tree inference formats directly, exposing the underlying markup to data-mining services. The library source code, extensive documentation and live examples are freely accessible at www.jsphylosvg.com.

An integrated inspection of the somatic mutations in a lung squamous cell carcinoma using next-generation sequencing.

Directory of Open Access Journals (Sweden)

Lucy F Stead

Full Text Available Squamous cell carcinoma (SCC of the lung kills over 350,000 people annually worldwide, and is the main lung cancer histotype with no targeted treatments. High-coverage whole-genome sequencing of the other main subtypes, small-cell and adenocarcinoma, gave insights into carcinogenic mechanisms and disease etiology. The genomic complexity within the lung SCC subtype, as revealed by The Cancer Genome Atlas, means this subtype is likely to benefit from a more integrated approach in which the transcriptional consequences of somatic mutations are simultaneously inspected. Here we present such an approach: the integrated analysis of deep sequencing data from both the whole genome and whole transcriptome (coding and non-coding of LUDLU-1, a SCC lung cell line. Our results show that LUDLU-1 lacks the mutational signature that has been previously associated with tobacco exposure in other lung cancer subtypes, and suggests that DNA-repair efficiency is adversely affected; LUDLU-1 contains somatic mutations in TP53 and BRCA2, allelic imbalance in the expression of two cancer-associated BRCA1 germline polymorphisms and reduced transcription of a potentially endogenous PARP2 inhibitor. Functional assays were performed and compared with a control lung cancer cell line. LUDLU-1 did not exhibit radiosensitisation or an increase in sensitivity to PARP inhibitors. However, LUDLU-1 did exhibit small but significant differences with respect to cisplatin sensitivity. Our research shows how integrated analyses of high-throughput data can generate hypotheses to be tested in the lab.

PHYLOGEOrec: A QGIS plugin for spatial phylogeographic reconstruction from phylogenetic tree and geographical information data

Science.gov (United States)

Nashrulloh, Maulana Malik; Kurniawan, Nia; Rahardi, Brian

2017-11-01

The increasing availability of genetic sequence data associated with explicit geographic and environment (including biotic and abiotic components) information offers new opportunities to study the processes that shape biodiversity and its patterns. Developing phylogeography reconstruction, by integrating phylogenetic and biogeographic knowledge, provides richer and deeper visualization and information on diversification events than ever before. Geographical information systems such as QGIS provide an environment for spatial modeling, analysis, and dissemination by which phylogenetic models can be explicitly linked with their associated spatial data, and subsequently, they will be integrated with other related georeferenced datasets describing the biotic and abiotic environment. We are introducing PHYLOGEOrec, a QGIS plugin for building spatial phylogeographic reconstructions constructed from phylogenetic tree and geographical information data based on QGIS2threejs. By using PHYLOGEOrec, researchers can integrate existing phylogeny and geographical information data, resulting in three-dimensional geographic visualizations of phylogenetic trees in the Keyhole Markup Language (KML) format. Such formats can be overlaid on a map using QGIS and finally, spatially viewed in QGIS by means of a QGIS2threejs engine for further analysis. KML can also be viewed in reputable geobrowsers with KML-support (i.e., Google Earth).

Structural analysis and dimerization profile of the SCAN domain of the pluripotency factor Zfp206

KAUST Repository

Liang, Yu

2012-06-26

Zfp206 (also named as Zscan10) belongs to the subfamily of C2H2 zinc finger transcription factors, which is characterized by the N-terminal SCAN domain. The SCAN domain mediates self-association and association between the members of SCAN family transcription factors, but the structural basis and selectivity determinants for complex formation is unknown. Zfp206 is important for maintaining the pluripotency of embryonic stem cells presumably by combinatorial assembly of itself or other SCAN family members on enhancer regions. To gain insights into the folding topology and selectivity determinants for SCAN dimerization, we solved the 1.85 crystal structure of the SCAN domain of Zfp206. In vitro binding studies using a panel of 20 SCAN proteins indicate that the SCAN domain Zfp206 can selectively associate with other members of SCAN family transcription factors. Deletion mutations showed that the N-terminal helix 1 is critical for heterodimerization. Double mutations and multiple mutations based on the Zfp206SCAN-Zfp110SCAN model suggested that domain swapped topology is a possible preference for Zfp206SCAN-Zfp110SCAN heterodimer. Together, we demonstrate that the Zfp206SCAN constitutes a protein module that enables C2H2 transcription factor dimerization in a highly selective manner using a domain-swapped interface architecture and identify novel partners for Zfp206 during embryonal development. 2012 The Author(s).

Structural analysis and dimerization profile of the SCAN domain of the pluripotency factor Zfp206

KAUST Repository

Liang, Yu; Huimei Hong, Felicia; Ganesan, Pugalenthi; Jiang, Sizun; Jauch, Ralf; Stanton, Lawrence W.; Kolatkar, Prasanna R.

2012-01-01

Zfp206 (also named as Zscan10) belongs to the subfamily of C2H2 zinc finger transcription factors, which is characterized by the N-terminal SCAN domain. The SCAN domain mediates self-association and association between the members of SCAN family transcription factors, but the structural basis and selectivity determinants for complex formation is unknown. Zfp206 is important for maintaining the pluripotency of embryonic stem cells presumably by combinatorial assembly of itself or other SCAN family members on enhancer regions. To gain insights into the folding topology and selectivity determinants for SCAN dimerization, we solved the 1.85 crystal structure of the SCAN domain of Zfp206. In vitro binding studies using a panel of 20 SCAN proteins indicate that the SCAN domain Zfp206 can selectively associate with other members of SCAN family transcription factors. Deletion mutations showed that the N-terminal helix 1 is critical for heterodimerization. Double mutations and multiple mutations based on the Zfp206SCAN-Zfp110SCAN model suggested that domain swapped topology is a possible preference for Zfp206SCAN-Zfp110SCAN heterodimer. Together, we demonstrate that the Zfp206SCAN constitutes a protein module that enables C2H2 transcription factor dimerization in a highly selective manner using a domain-swapped interface architecture and identify novel partners for Zfp206 during embryonal development. 2012 The Author(s).

Multiplex fluorescence melting curve analysis for mutation detection with dual-labeled, self-quenched probes.

Directory of Open Access Journals (Sweden)

Qiuying Huang

2011-04-01

Full Text Available Probe-based fluorescence melting curve analysis (FMCA is a powerful tool for mutation detection based on melting temperature generated by thermal denaturation of the probe-target hybrid. Nevertheless, the color multiplexing, probe design, and cross-platform compatibility remain to be limited by using existing probe chemistries. We hereby explored two dual-labeled, self-quenched probes, TaqMan and shared-stem molecular beacons, in their ability to conduct FMCA. Both probes could be directly used for FMCA and readily integrated with closed-tube amplicon hybridization under asymmetric PCR conditions. Improved flexibility of FMCA by using these probes was illustrated in three representative applications of FMCA: mutation scanning, mutation identification and mutation genotyping, all of which achieved improved color-multiplexing with easy probe design and versatile probe combination and all were validated with a large number of real clinical samples. The universal cross-platform compatibility of these probes-based FMCA was also demonstrated by a 4-color mutation genotyping assay performed on five different real-time PCR instruments. The dual-labeled, self-quenched probes offered unprecedented combined advantage of enhanced multiplexing, improved flexibility in probe design, and expanded cross-platform compatibility, which would substantially improve FMCA in mutation detection of various applications.

Changed membrane integration and catalytic site conformation are two mechanisms behind the increased Aβ42/Aβ40 ratio by presenilin 1 familial Alzheimer-linked mutations

Directory of Open Access Journals (Sweden)

Johanna Wanngren

2014-01-01

Full Text Available The enzyme complex γ-secretase generates amyloid β-peptide (Aβ, a 37–43-residue peptide associated with Alzheimer disease (AD. Mutations in presenilin 1 (PS1, the catalytical subunit of γ-secretase, result in familial AD (FAD. A unifying theme among FAD mutations is an alteration in the ratio Aβ species produced (the Aβ42/Aβ40 ratio, but the molecular mechanisms responsible remain elusive. In this report we have studied the impact of several different PS1 FAD mutations on the integration of selected PS1 transmembrane domains and on PS1 active site conformation, and whether any effects translate to a particular amyloid precursor protein (APP processing phenotype. Most mutations studied caused an increase in the Aβ42/Aβ40 ratio, but via different mechanisms. The mutations that caused a particular large increase in the Aβ42/Aβ40 ratio did also display an impaired APP intracellular domain (AICD formation and a lower total Aβ production. Interestingly, seven mutations close to the catalytic site caused a severely impaired integration of proximal transmembrane/hydrophobic sequences into the membrane. This structural defect did not correlate to a particular APP processing phenotype. Six selected FAD mutations, all of which exhibited different APP processing profiles and impact on PS1 transmembrane domain integration, were found to display an altered active site conformation. Combined, our data suggest that FAD mutations affect the PS1 structure and active site differently, resulting in several complex APP processing phenotypes, where the most aggressive mutations in terms of increased Aβ42/Aβ40 ratio are associated with a decrease in total γ-secretase activity.

Epitope discovery with phylogenetic hidden Markov models.

LENUS (Irish Health Repository)

Lacerda, Miguel

2010-05-01

Existing methods for the prediction of immunologically active T-cell epitopes are based on the amino acid sequence or structure of pathogen proteins. Additional information regarding the locations of epitopes may be acquired by considering the evolution of viruses in hosts with different immune backgrounds. In particular, immune-dependent evolutionary patterns at sites within or near T-cell epitopes can be used to enhance epitope identification. We have developed a mutation-selection model of T-cell epitope evolution that allows the human leukocyte antigen (HLA) genotype of the host to influence the evolutionary process. This is one of the first examples of the incorporation of environmental parameters into a phylogenetic model and has many other potential applications where the selection pressures exerted on an organism can be related directly to environmental factors. We combine this novel evolutionary model with a hidden Markov model to identify contiguous amino acid positions that appear to evolve under immune pressure in the presence of specific host immune alleles and that therefore represent potential epitopes. This phylogenetic hidden Markov model provides a rigorous probabilistic framework that can be combined with sequence or structural information to improve epitope prediction. As a demonstration, we apply the model to a data set of HIV-1 protein-coding sequences and host HLA genotypes.

Novel folliculin (FLCN) mutation and familial spontaneous pneumothorax.

Science.gov (United States)

Zhu, J-F; Shen, X-Q; Zhu, F; Tian, L

2017-01-01

Familial spontaneous pneumothorax is one of the characteristics of Birt-Hogg-Dubé syndrome (BHDS), which is an autosomal dominant disease caused by the mutation of folliculin (FLCN). To investigate the mutation of FLCN gene in a familial spontaneous pneumothorax. Prospective case study. Clinical and genetic data of a Chinese family with four patients who presented spontaneous pneumothorax in the absence of skin lesions or renal tumors were collected. CT scan of patient's lung was applied for observation of pneumothorax. DNA sequencing of the coding exons (4-14 exons) of FLCN was performed for all 11 members of the family and 100 unrelated healthy controls. CT scan of patient's lung showed spontaneous pneumothorax. A mutation (c. 510C > G) that leads to a premature stop codon (p. Y170X) was found in the proband using DNA sequencing of coding exons (4-14 exons) of FLCN. This mutation was also observed in the other affected members of the family. A nonsense mutation of FLCN was found in a spontaneous pneumothorax family. Our results expand the mutational spectrum of FLCN in patients with BHDS. © The Author 2016. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Integrating evolution into geographical ecology: a phylogenetic perspective on palm distributions and community composition across scales

DEFF Research Database (Denmark)

Eiserhardt, Wolf L.; Svenning, J.-C.; Kissling, W. Daniel

in 430 transects in the Western Amazon, b) a set of range maps for all American palms (550 spp.), and c) global country-level presence/ absence data of all (>2400) palm species. These data were analysed with novel phylogenetic community structure and turnover methods. Globally, the phylogenetic structure...

Monolithically Integrated, Mechanically Resilient Carbon-Based Probes for Scanning Probe Microscopy

Science.gov (United States)

Kaul, Anupama B.; Megerian, Krikor G.; Jennings, Andrew T.; Greer, Julia R.

2010-01-01

Scanning probe microscopy (SPM) is an important tool for performing measurements at the nanoscale in imaging bacteria or proteins in biology, as well as in the electronics industry. An essential element of SPM is a sharp, stable tip that possesses a small radius of curvature to enhance spatial resolution. Existing techniques for forming such tips are not ideal. High-aspect-ratio, monolithically integrated, as-grown carbon nanofibers (CNFs) have been formed that show promise for SPM applications by overcoming the limitations present in wet chemical and separate substrate etching processes.

Nosocomial HIV-transmission in an outpatient clinic detected by epidemiologicaland phylogenetic analyses

DEFF Research Database (Denmark)

Katzenstein, T.L.; Jørgensen, L.B.; H, Permin

1999-01-01

.9% respectively. In addition, GP harboured HIV RNA with a foscarnet resistance mutation further lendingsupport to virus from the foscarnet-treated FDL being the source of the infection. Interestingly, GP experienced increases inimmunoglobulin production after contracting the HIV-infection, and decreases after...... antiretroviral-induced viral suppression. Aclinical procedure which, under stressful conditions, could lead to breaches in infection control measures was identified. The source ofthe infection was most likely a contaminated multidose vial. CONCLUSION: Through epidemiological and phylogenetic analyses acase...

Phylogenetic congruence between subtropical trees and their associated fungi.

Science.gov (United States)

Liu, Xubing; Liang, Minxia; Etienne, Rampal S; Gilbert, Gregory S; Yu, Shixiao

2016-12-01

Recent studies have detected phylogenetic signals in pathogen-host networks for both soil-borne and leaf-infecting fungi, suggesting that pathogenic fungi may track or coevolve with their preferred hosts. However, a phylogenetically concordant relationship between multiple hosts and multiple fungi in has rarely been investigated. Using next-generation high-throughput DNA sequencing techniques, we analyzed fungal taxa associated with diseased leaves, rotten seeds, and infected seedlings of subtropical trees. We compared the topologies of the phylogenetic trees of the soil and foliar fungi based on the internal transcribed spacer (ITS) region with the phylogeny of host tree species based on matK , rbcL , atpB, and 5.8S genes. We identified 37 foliar and 103 soil pathogenic fungi belonging to the Ascomycota and Basidiomycota phyla and detected significantly nonrandom host-fungus combinations, which clustered on both the fungus phylogeny and the host phylogeny. The explicit evidence of congruent phylogenies between tree hosts and their potential fungal pathogens suggests either diffuse coevolution among the plant-fungal interaction networks or that the distribution of fungal species tracked spatially associated hosts with phylogenetically conserved traits and habitat preferences. Phylogenetic conservatism in plant-fungal interactions within a local community promotes host and parasite specificity, which is integral to the important role of fungi in promoting species coexistence and maintaining biodiversity of forest communities.

Pairagon+N-SCAN_EST: a model-based gene annotation pipeline

DEFF Research Database (Denmark)

Arumugam, Manimozhiyan; Wei, Chaochun; Brown, Randall H

2006-01-01

This paper describes Pairagon+N-SCAN_EST, a gene annotation pipeline that uses only native alignments. For each expressed sequence it chooses the best genomic alignment. Systems like ENSEMBL and ExoGean rely on trans alignments, in which expressed sequences are aligned to the genomic loci...... with de novo gene prediction by using N-SCAN_EST. N-SCAN_EST is based on a generalized HMM probability model augmented with a phylogenetic conservation model and EST alignments. It can predict complete transcripts by extending or merging EST alignments, but it can also predict genes in regions without EST...

Deleterious mutation accumulation in organelle genomes.

Science.gov (United States)

Lynch, M; Blanchard, J L

1998-01-01

It is well established on theoretical grounds that the accumulation of mildly deleterious mutations in nonrecombining genomes is a major extinction risk in obligately asexual populations. Sexual populations can also incur mutational deterioration in genomic regions that experience little or no recombination, i.e., autosomal regions near centromeres, Y chromosomes, and organelle genomes. Our results suggest, for a wide array of genes (transfer RNAs, ribosomal RNAs, and proteins) in a diverse collection of species (animals, plants, and fungi), an almost universal increase in the fixation probabilities of mildly deleterious mutations arising in mitochondrial and chloroplast genomes relative to those arising in the recombining nuclear genome. This enhanced width of the selective sieve in organelle genomes does not appear to be a consequence of relaxed selection, but can be explained by the decline in the efficiency of selection that results from the reduction of effective population size induced by uniparental inheritance. Because of the very low mutation rates of organelle genomes (on the order of 10(-4) per genome per year), the reduction in fitness resulting from mutation accumulation in such genomes is a very long-term process, not likely to imperil many species on time scales of less than a million years, but perhaps playing some role in phylogenetic lineage sorting on time scales of 10 to 100 million years.

CLOSE RANGE HYPERSPECTRAL IMAGING INTEGRATED WITH TERRESTRIAL LIDAR SCANNING APPLIED TO ROCK CHARACTERISATION AT CENTIMETRE SCALE

Directory of Open Access Journals (Sweden)

T. H. Kurz

2012-07-01

Full Text Available Compact and lightweight hyperspectral imagers allow the application of close range hyperspectral imaging with a ground based scanning setup for geological fieldwork. Using such a scanning setup, steep cliff sections and quarry walls can be scanned with a more appropriate viewing direction and a higher image resolution than from airborne and spaceborne platforms. Integration of the hyperspectral imagery with terrestrial lidar scanning provides the hyperspectral information in a georeferenced framework and enables measurement at centimetre scale. In this paper, three geological case studies are used to demonstrate the potential of this method for rock characterisation. Two case studies are applied to carbonate quarries where mapping of different limestone and dolomite types was required, as well as measurements of faults and layer thicknesses from inaccessible parts of the quarries. The third case study demonstrates the method using artificial lighting, applied in a subsurface scanning scenario where solar radiation cannot be utilised.

Mitochondrial Mutation Rate, Spectrum and Heteroplasmy in Caenorhabditis elegans Spontaneous Mutation Accumulation Lines of Differing Population Size.

Science.gov (United States)

Konrad, Anke; Thompson, Owen; Waterston, Robert H; Moerman, Donald G; Keightley, Peter D; Bergthorsson, Ulfar; Katju, Vaishali

2017-06-01

Mitochondrial genomes of metazoans, given their elevated rates of evolution, have served as pivotal markers for phylogeographic studies and recent phylogenetic events. In order to determine the dynamics of spontaneous mitochondrial mutations in small populations in the absence and presence of selection, we evolved mutation accumulation (MA) lines of Caenorhabditis elegans in parallel over 409 consecutive generations at three varying population sizes of N = 1, 10, and 100 hermaphrodites. The N =1 populations should have a minimal influence of natural selection to provide the spontaneous mutation rate and the expected rate of neutral evolution, whereas larger population sizes should experience increasing intensity of selection. New mutations were identified by Illumina paired-end sequencing of 86 mtDNA genomes across 35 experimental lines and compared with published genomes of natural isolates. The spontaneous mitochondrial mutation rate was estimated at 1.05 × 10-7/site/generation. A strong G/C→A/T mutational bias was observed in both the MA lines and the natural isolates. This suggests that the low G + C content at synonymous sites is the product of mutation bias rather than selection as previously proposed. The mitochondrial effective population size per worm generation was estimated to be 62. Although it was previously concluded that heteroplasmy was rare in C. elegans, the vast majority of mutations in this study were heteroplasmic despite an experimental regime exceeding 400 generations. The frequencies of frameshift and nonsynonymous mutations were negatively correlated with population size, which suggests their deleterious effects on fitness and a potent role for selection in their eradication. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Clustering of Caucasian Leber hereditary optic neuropathy patients containing the 11778 or 14484 mutations on an mtDNA lineage

Energy Technology Data Exchange (ETDEWEB)

Brown, M.D.; Sun, F.; Wallace, D.C. [Emory Univ. School of Medicine, Atlanta, GA (United States)

1997-02-01

Leber hereditary optic neuropathy (LHON) is a type of blindness caused by mtDNA mutations. Three LHON mtDNA mutations at nucleotide positions 3460, 11778, and 14484 are specific for LHON and account for 90% of worldwide cases and are thus designated as {open_quotes}primary{close_quotes} LHON mutations. Fifteen other {open_quotes}secondary{close_quotes} LHON mtDNA mutations have been identified, but their pathogenicity is unclear. mtDNA haplotype and phylogenetic analysis of the primary LHON mutations in North American Caucasian patients and controls has shown that, unlike the 3460 and 11778 mutations, which are distributed throughout the European-derived (Caucasian) mtDNA phylogeny, patients containing the 14484 mutation tended to be associated with European mtDNA haplotype J. To investigate this apparent clustering, we performed {chi}{sup 2}-based statistical analyses to compare the distribution of LHON patients on the Caucasian phylogenetic tree. Our results indicate that, unlike the 3460 and 11778 mutations, the 14484 mutation was not distributed on the phylogeny in proportion to the frequencies of the major Caucasian mtDNA haplogroups found in North America. The 14484 mutation was next shown to occur on the haplogroup J background more frequently that expected, consistent with the observation that {approximately}75% of worldwide 14484-positive LHON patients occur in association with haplogroup J. The 11778 mutation also exhibited a moderate clustering on haplogroup J. These observations were supported by statistical analysis using all available mutation frequencies reported in the literature. This paper thus illustrates the potential importance of genetic background in certain mtDNA-based diseases, speculates on a pathogenic role for a subset of LHON secondary mutations and their interaction with primary mutations, and provides support for a polygenic model for LHON expression in some cases. 18 refs., 3 tabs.

Monogenean anchor morphometry: systematic value, phylogenetic signal, and evolution

Science.gov (United States)

Soo, Oi Yoon Michelle; Tan, Wooi Boon; Lim, Lee Hong Susan

2016-01-01

Background. Anchors are one of the important attachment appendages for monogenean parasites. Common descent and evolutionary processes have left their mark on anchor morphometry, in the form of patterns of shape and size variation useful for systematic and evolutionary studies. When combined with morphological and molecular data, analysis of anchor morphometry can potentially answer a wide range of biological questions. Materials and Methods. We used data from anchor morphometry, body size and morphology of 13 Ligophorus (Monogenea: Ancyrocephalidae) species infecting two marine mugilid (Teleostei: Mugilidae) fish hosts: Moolgarda buchanani (Bleeker) and Liza subviridis (Valenciennes) from Malaysia. Anchor shape and size data (n = 530) were generated using methods of geometric morphometrics. We used 28S rRNA, 18S rRNA, and ITS1 sequence data to infer a maximum likelihood phylogeny. We discriminated species using principal component and cluster analysis of shape data. Adams’s Kmult was used to detect phylogenetic signal in anchor shape. Phylogeny-correlated size and shape changes were investigated using continuous character mapping and directional statistics, respectively. We assessed morphological constraints in anchor morphometry using phylogenetic regression of anchor shape against body size and anchor size. Anchor morphological integration was studied using partial least squares method. The association between copulatory organ morphology and anchor shape and size in phylomorphospace was used to test the Rohde-Hobbs hypothesis. We created monogeneaGM, a new R package that integrates analyses of monogenean anchor geometric morphometric data with morphological and phylogenetic data. Results. We discriminated 12 of the 13 Ligophorus species using anchor shape data. Significant phylogenetic signal was detected in anchor shape. Thus, we discovered new morphological characters based on anchor shaft shape, the length between the inner root point and the outer root

CAD-based intelligent robot system integrated with 3D scanning for shoe roughing and cementing

Directory of Open Access Journals (Sweden)

Chiu Cheng-Chang

2017-01-01

Full Text Available Roughing and cementing are very essential to the process of bonding shoe uppers and the corresponding soles; however, for shoes with complicated design, such as sport shoes, roughing and cementing greatly relied on manual operation. Recently, shoe industry is progressing to 3D design, thus 3D model of the shoe upper and sole will be created before launching into mass production. Taking advantage of the 3D model, this study developed a plug-in program on Rhino 3D CAD platform, which realized the complicated roughing and cementing route planning to be performed by the plug-in program, integrated with real-time 3D scanning information to compensate the planned route, and then converted to working trajectory of robot arm to implement roughing and cementing. The proposed 3D CAD-based intelligent robot arm system integrated with 3D scanning for shoe roughing and cementing is realized and proved to be feasible.

The visual air quality predicted by conventional and scanning teleradiometers and an integrating nephelometer

Energy Technology Data Exchange (ETDEWEB)

Malm, W [U.S. Environmental Protection Agency, Las Vegas, NV; Pitchford, A; Tree, R; Walther, E; Pearson, M; Archer, S

1981-12-01

Many Class I areas have unique vistas which require an observer to look over complex terrain containing basins, valleys, and canyons. These topographic features tend to form pollution ''basins'' and ''corridors'' that trap and funnel air pollutants under certain meteorological conditions. For example, on numerous days, layers of haze in the San Juan River Basin obscure various vista elements including the Chuska Mountains as viewed from Mesa Verde National Park, CO. Measrements by an integrating nephelometer and conventional teleradiometer at one location in Mesa Verde do not quantify inhomogeneities. In this paper, data from these instruments are compated to data derived from scanning teleradiometer measurements of photographic slide images. The slides, surrogates of the real three-dimensional scene, were projected and scanned to determine relative sky and vista radiance at 40 points within a vertical slice of the vista. Comparison of the corresponding visual range data sets for each instrument for September and December 1979 demonstrates the utility of the scanning teleradiometer.

XplorSeq: a software environment for integrated management and phylogenetic analysis of metagenomic sequence data.

Science.gov (United States)

Frank, Daniel N

2008-10-07

Advances in automated DNA sequencing technology have accelerated the generation of metagenomic DNA sequences, especially environmental ribosomal RNA gene (rDNA) sequences. As the scale of rDNA-based studies of microbial ecology has expanded, need has arisen for software that is capable of managing, annotating, and analyzing the plethora of diverse data accumulated in these projects. XplorSeq is a software package that facilitates the compilation, management and phylogenetic analysis of DNA sequences. XplorSeq was developed for, but is not limited to, high-throughput analysis of environmental rRNA gene sequences. XplorSeq integrates and extends several commonly used UNIX-based analysis tools by use of a Macintosh OS-X-based graphical user interface (GUI). Through this GUI, users may perform basic sequence import and assembly steps (base-calling, vector/primer trimming, contig assembly), perform BLAST (Basic Local Alignment and Search Tool; 123) searches of NCBI and local databases, create multiple sequence alignments, build phylogenetic trees, assemble Operational Taxonomic Units, estimate biodiversity indices, and summarize data in a variety of formats. Furthermore, sequences may be annotated with user-specified meta-data, which then can be used to sort data and organize analyses and reports. A document-based architecture permits parallel analysis of sequence data from multiple clones or amplicons, with sequences and other data stored in a single file. XplorSeq should benefit researchers who are engaged in analyses of environmental sequence data, especially those with little experience using bioinformatics software. Although XplorSeq was developed for management of rDNA sequence data, it can be applied to most any sequencing project. The application is available free of charge for non-commercial use at http://vent.colorado.edu/phyloware.

Molecular Clock of Neutral Mutations in a Fitness-Increasing Evolutionary Process.

Science.gov (United States)

Kishimoto, Toshihiko; Ying, Bei-Wen; Tsuru, Saburo; Iijima, Leo; Suzuki, Shingo; Hashimoto, Tomomi; Oyake, Ayana; Kobayashi, Hisaka; Someya, Yuki; Narisawa, Dai; Yomo, Tetsuya

2015-07-01

The molecular clock of neutral mutations, which represents linear mutation fixation over generations, is theoretically explained by genetic drift in fitness-steady evolution or hitchhiking in adaptive evolution. The present study is the first experimental demonstration for the molecular clock of neutral mutations in a fitness-increasing evolutionary process. The dynamics of genome mutation fixation in the thermal adaptive evolution of Escherichia coli were evaluated in a prolonged evolution experiment in duplicated lineages. The cells from the continuously fitness-increasing evolutionary process were subjected to genome sequencing and analyzed at both the population and single-colony levels. Although the dynamics of genome mutation fixation were complicated by the combination of the stochastic appearance of adaptive mutations and clonal interference, the mutation fixation in the population was simply linear over generations. Each genome in the population accumulated 1.6 synonymous and 3.1 non-synonymous neutral mutations, on average, by the spontaneous mutation accumulation rate, while only a single genome in the population occasionally acquired an adaptive mutation. The neutral mutations that preexisted on the single genome hitchhiked on the domination of the adaptive mutation. The successive fixation processes of the 128 mutations demonstrated that hitchhiking and not genetic drift were responsible for the coincidence of the spontaneous mutation accumulation rate in the genome with the fixation rate of neutral mutations in the population. The molecular clock of neutral mutations to the fitness-increasing evolution suggests that the numerous neutral mutations observed in molecular phylogenetic trees may not always have been fixed in fitness-steady evolution but in adaptive evolution.

Molecular Clock of Neutral Mutations in a Fitness-Increasing Evolutionary Process.

Directory of Open Access Journals (Sweden)

Toshihiko Kishimoto

2015-07-01

Full Text Available The molecular clock of neutral mutations, which represents linear mutation fixation over generations, is theoretically explained by genetic drift in fitness-steady evolution or hitchhiking in adaptive evolution. The present study is the first experimental demonstration for the molecular clock of neutral mutations in a fitness-increasing evolutionary process. The dynamics of genome mutation fixation in the thermal adaptive evolution of Escherichia coli were evaluated in a prolonged evolution experiment in duplicated lineages. The cells from the continuously fitness-increasing evolutionary process were subjected to genome sequencing and analyzed at both the population and single-colony levels. Although the dynamics of genome mutation fixation were complicated by the combination of the stochastic appearance of adaptive mutations and clonal interference, the mutation fixation in the population was simply linear over generations. Each genome in the population accumulated 1.6 synonymous and 3.1 non-synonymous neutral mutations, on average, by the spontaneous mutation accumulation rate, while only a single genome in the population occasionally acquired an adaptive mutation. The neutral mutations that preexisted on the single genome hitchhiked on the domination of the adaptive mutation. The successive fixation processes of the 128 mutations demonstrated that hitchhiking and not genetic drift were responsible for the coincidence of the spontaneous mutation accumulation rate in the genome with the fixation rate of neutral mutations in the population. The molecular clock of neutral mutations to the fitness-increasing evolution suggests that the numerous neutral mutations observed in molecular phylogenetic trees may not always have been fixed in fitness-steady evolution but in adaptive evolution.

Untangling hybrid phylogenetic signals: horizontal gene transfer and artifacts of phylogenetic reconstruction.

Science.gov (United States)

Beiko, Robert G; Ragan, Mark A

2009-01-01

Phylogenomic methods can be used to investigate the tangled evolutionary relationships among genomes. Building 'all the trees of all the genes' can potentially identify common pathways of horizontal gene transfer (HGT) among taxa at varying levels of phylogenetic depth. Phylogenetic affinities can be aggregated and merged with the information about genetic linkage and biochemical function to examine hypotheses of adaptive evolution via HGT. Additionally, the use of many genetic data sets increases the power of statistical tests for phylogenetic artifacts. However, large-scale phylogenetic analyses pose several challenges, including the necessary abandonment of manual validation techniques, the need to translate inferred phylogenetic discordance into inferred HGT events, and the challenges involved in aggregating results from search-based inference methods. In this chapter we describe a tree search procedure to recover the most parsimonious pathways of HGT, and examine some of the assumptions that are made by this method.

Molecular nature of X-ray-induced mutations compared with that of spontaneous ones in human c-hprt gene integrated into mammalian chromosomal DNA

International Nuclear Information System (INIS)

Kimura, Hiroshi; Kato, Takesi.

1992-01-01

X-ray-induced mutations were analysed at molecular levels in comparison with spontaneous mutations. Altered sequences were determined tentatively of 30 independent X-ray-induced mutations in a cDNA of the human hprt gene which was integrated into mammalian chromosome as a part of a shuttle vector. Mutations consisted of base substitutions (37 %), frameshifts (27 %), deletions (27 %) and others (10 %). All these mutational events were distributed randomly over the gene without there being hot spots. The spectrum and distribution of X-ray-induced mutations resembled those of spontaneous mutations. Among base substitutions, transversions were predominant and base substitution mutations occurred more at A:T sites than at G:C sites, which is also the case in spontaneous mutations. Most of the frameshift and deletion mutations induced by X-rays, as well as those spontaneously arising, were characterized by the existence of short direct repeats of several identical bases in a row at the sites of the mutations. A slippage misalignment mechanism in replication well accounts for the generation of these classes of mutations. Judging from the data accumulated so far, it can be concluded that X-ray-induced mutations at molecular levels are similar to those spontaneously occurring. (author)

Relating phylogenetic trees to transmission trees of infectious disease outbreaks.

Science.gov (United States)

Ypma, Rolf J F; van Ballegooijen, W Marijn; Wallinga, Jacco

2013-11-01

Transmission events are the fundamental building blocks of the dynamics of any infectious disease. Much about the epidemiology of a disease can be learned when these individual transmission events are known or can be estimated. Such estimations are difficult and generally feasible only when detailed epidemiological data are available. The genealogy estimated from genetic sequences of sampled pathogens is another rich source of information on transmission history. Optimal inference of transmission events calls for the combination of genetic data and epidemiological data into one joint analysis. A key difficulty is that the transmission tree, which describes the transmission events between infected hosts, differs from the phylogenetic tree, which describes the ancestral relationships between pathogens sampled from these hosts. The trees differ both in timing of the internal nodes and in topology. These differences become more pronounced when a higher fraction of infected hosts is sampled. We show how the phylogenetic tree of sampled pathogens is related to the transmission tree of an outbreak of an infectious disease, by the within-host dynamics of pathogens. We provide a statistical framework to infer key epidemiological and mutational parameters by simultaneously estimating the phylogenetic tree and the transmission tree. We test the approach using simulations and illustrate its use on an outbreak of foot-and-mouth disease. The approach unifies existing methods in the emerging field of phylodynamics with transmission tree reconstruction methods that are used in infectious disease epidemiology.

Model checking software for phylogenetic trees using distribution and database methods

Directory of Open Access Journals (Sweden)

Requeno José Ignacio

2013-12-01

Full Text Available Model checking, a generic and formal paradigm stemming from computer science based on temporal logics, has been proposed for the study of biological properties that emerge from the labeling of the states defined over the phylogenetic tree. This strategy allows us to use generic software tools already present in the industry. However, the performance of traditional model checking is penalized when scaling the system for large phylogenies. To this end, two strategies are presented here. The first one consists of partitioning the phylogenetic tree into a set of subgraphs each one representing a subproblem to be verified so as to speed up the computation time and distribute the memory consumption. The second strategy is based on uncoupling the information associated to each state of the phylogenetic tree (mainly, the DNA sequence and exporting it to an external tool for the management of large information systems. The integration of all these approaches outperforms the results of monolithic model checking and helps us to execute the verification of properties in a real phylogenetic tree.

Digitally controlled analog proportional-integral-derivative (PID) controller for high-speed scanning probe microscopy

Science.gov (United States)

Dukic, Maja; Todorov, Vencislav; Andany, Santiago; Nievergelt, Adrian P.; Yang, Chen; Hosseini, Nahid; Fantner, Georg E.

2017-12-01

Nearly all scanning probe microscopes (SPMs) contain a feedback controller, which is used to move the scanner in the direction of the z-axis in order to maintain a constant setpoint based on the tip-sample interaction. The most frequently used feedback controller in SPMs is the proportional-integral (PI) controller. The bandwidth of the PI controller presents one of the speed limiting factors in high-speed SPMs, where higher bandwidths enable faster scanning speeds and higher imaging resolution. Most SPM systems use digital signal processor-based PI feedback controllers, which require analog-to-digital and digital-to-analog converters. These converters introduce additional feedback delays which limit the achievable imaging speed and resolution. In this paper, we present a digitally controlled analog proportional-integral-derivative (PID) controller. The controller implementation allows tunability of the PID gains over a large amplification and frequency range, while also providing precise control of the system and reproducibility of the gain parameters. By using the analog PID controller, we were able to perform successful atomic force microscopy imaging of a standard silicon calibration grating at line rates up to several kHz.

Bayesian phylogenetic estimation of fossil ages.

Science.gov (United States)

Drummond, Alexei J; Stadler, Tanja

2016-07-19

Recent advances have allowed for both morphological fossil evidence and molecular sequences to be integrated into a single combined inference of divergence dates under the rule of Bayesian probability. In particular, the fossilized birth-death tree prior and the Lewis-Mk model of discrete morphological evolution allow for the estimation of both divergence times and phylogenetic relationships between fossil and extant taxa. We exploit this statistical framework to investigate the internal consistency of these models by producing phylogenetic estimates of the age of each fossil in turn, within two rich and well-characterized datasets of fossil and extant species (penguins and canids). We find that the estimation accuracy of fossil ages is generally high with credible intervals seldom excluding the true age and median relative error in the two datasets of 5.7% and 13.2%, respectively. The median relative standard error (RSD) was 9.2% and 7.2%, respectively, suggesting good precision, although with some outliers. In fact, in the two datasets we analyse, the phylogenetic estimate of fossil age is on average less than 2 Myr from the mid-point age of the geological strata from which it was excavated. The high level of internal consistency found in our analyses suggests that the Bayesian statistical model employed is an adequate fit for both the geological and morphological data, and provides evidence from real data that the framework used can accurately model the evolution of discrete morphological traits coded from fossil and extant taxa. We anticipate that this approach will have diverse applications beyond divergence time dating, including dating fossils that are temporally unconstrained, testing of the 'morphological clock', and for uncovering potential model misspecification and/or data errors when controversial phylogenetic hypotheses are obtained based on combined divergence dating analyses.This article is part of the themed issue 'Dating species divergences using

Evolution of the Pseudomonas aeruginosa mutational resistome in an international Cystic Fibrosis clone.

Science.gov (United States)

López-Causapé, Carla; Sommer, Lea Mette; Cabot, Gabriel; Rubio, Rosa; Ocampo-Sosa, Alain A; Johansen, Helle Krogh; Figuerola, Joan; Cantón, Rafael; Kidd, Timothy J; Molin, Soeren; Oliver, Antonio

2017-07-17

Emergence of epidemic clones and antibiotic resistance development compromises the management of Pseudomonas aeruginosa cystic fibrosis (CF) chronic respiratory infections. Whole genome sequencing (WGS) was used to decipher the phylogeny, interpatient dissemination, WGS mutator genotypes (mutome) and resistome of a widespread clone (CC274), in isolates from two highly-distant countries, Australia and Spain, covering an 18-year period. The coexistence of two divergent CC274 clonal lineages was revealed, but without evident geographical barrier; phylogenetic reconstructions and mutational resistome demonstrated the interpatient transmission of mutators. The extraordinary capacity of P. aeruginosa to develop resistance was evidenced by the emergence of mutations in >100 genes related to antibiotic resistance during the evolution of CC274, catalyzed by mutator phenotypes. While the presence of classical mutational resistance mechanisms was confirmed and correlated with resistance phenotypes, results also showed a major role of unexpected mutations. Among them, PBP3 mutations, shaping up β-lactam resistance, were noteworthy. A high selective pressure for mexZ mutations was evidenced, but we showed for the first time that high-level aminoglycoside resistance in CF is likely driven by mutations in fusA1/fusA2, coding for elongation factor G. Altogether, our results provide valuable information for understanding the evolution of the mutational resistome of CF P. aeruginosa.

Nonbinary Tree-Based Phylogenetic Networks.

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Jetten, Laura; van Iersel, Leo

2018-01-01

Rooted phylogenetic networks are used to describe evolutionary histories that contain non-treelike evolutionary events such as hybridization and horizontal gene transfer. In some cases, such histories can be described by a phylogenetic base-tree with additional linking arcs, which can, for example, represent gene transfer events. Such phylogenetic networks are called tree-based. Here, we consider two possible generalizations of this concept to nonbinary networks, which we call tree-based and strictly-tree-based nonbinary phylogenetic networks. We give simple graph-theoretic characterizations of tree-based and strictly-tree-based nonbinary phylogenetic networks. Moreover, we show for each of these two classes that it can be decided in polynomial time whether a given network is contained in the class. Our approach also provides a new view on tree-based binary phylogenetic networks. Finally, we discuss two examples of nonbinary phylogenetic networks in biology and show how our results can be applied to them.

Inference of Tumor Phylogenies with Improved Somatic Mutation Discovery

KAUST Repository

Salari, Raheleh

2013-01-01

Next-generation sequencing technologies provide a powerful tool for studying genome evolution during progression of advanced diseases such as cancer. Although many recent studies have employed new sequencing technologies to detect mutations across multiple, genetically related tumors, current methods do not exploit available phylogenetic information to improve the accuracy of their variant calls. Here, we present a novel algorithm that uses somatic single nucleotide variations (SNVs) in multiple, related tissue samples as lineage markers for phylogenetic tree reconstruction. Our method then leverages the inferred phylogeny to improve the accuracy of SNV discovery. Experimental analyses demonstrate that our method achieves up to 32% improvement for somatic SNV calling of multiple related samples over the accuracy of GATK\\'s Unified Genotyper, the state of the art multisample SNV caller. © 2013 Springer-Verlag.

Exploring the determinants of phylogenetic diversity and assemblage structure in conifers across temporal, spatial, and taxonomic scales

DEFF Research Database (Denmark)

Eiserhardt, Wolf L.; Borchsenius, Finn; Sandel, Brody Steven

-environmental models are important elements in this framework. Here, we integrate both types of data in order to explore the determinants of forest tree diversity using the conifers as a model group. Conifers are an old, diverse (ca. 650 spp. in 6 families) and widespread group of woody plants of high ecological...... and economic importance. They are better studied than most other globally distributed groups of forest trees, allowing integrative studies with high phylogenetic and spatial resolution. We analyse phylogenetic diversity, assemblage structure, and diversification rates for regional conifer assemblages...

Asymptotics of steady states of a selection–mutation equation for small mutation rate

KAUST Repository

Calsina, Àngel

2013-12-01

We consider a selection-mutation equation for the density of individuals with respect to a continuous phenotypic evolutionary trait. We assume that the competition term for an individual with a given trait depends on the traits of all the other individuals, therefore giving an infinite-dimensional nonlinearity. Mutations are modelled by means of an integral operator. We prove existence of steady states and show that, when the mutation rate goes to zero, the asymptotic profile of the population is a Cauchy distribution. © Royal Society of Edinburgh 2013.

Asymptotics of steady states of a selection–mutation equation for small mutation rate

KAUST Repository

Calsina, À ngel; Cuadrado, Sí lvia; Desvillettes, Laurent; Raoul, Gaë l

2013-01-01

We consider a selection-mutation equation for the density of individuals with respect to a continuous phenotypic evolutionary trait. We assume that the competition term for an individual with a given trait depends on the traits of all the other individuals, therefore giving an infinite-dimensional nonlinearity. Mutations are modelled by means of an integral operator. We prove existence of steady states and show that, when the mutation rate goes to zero, the asymptotic profile of the population is a Cauchy distribution. © Royal Society of Edinburgh 2013.

Phylogenetic reconstruction and the identification of ancient polymorphism in the Bovini tribe (Bovidae, Bovinae

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MacEachern Sean

2009-04-01

Full Text Available Abstract Background The Bovinae subfamily incorporates an array of antelope, buffalo and cattle species. All of the members of this subfamily have diverged recently. Not surprisingly, a number of phylogenetic studies from molecular and morphological data have resulted in ambiguous trees and relationships amongst species, especially for Yak and Bison species. A partial phylogenetic reconstruction of 13 extant members of the Bovini tribe (Bovidae, Bovinae from 15 complete or partially sequenced autosomal genes is presented. Results We identified 3 distinct lineages after the Bovini split from the Boselaphini and Tragelaphini tribes, which has lead to the (1 Buffalo clade (Bubalus and Syncerus species and a more recent divergence leading to the (2 Banteng, Gaur and Mithan and (3 Domestic cattle clades. A fourth lineage may also exist that leads to Bison and Yak. However, there was some ambiguity as to whether this was a divergence from the Banteng/Gaur/Mithan or the Domestic cattle clade. From an analysis of approximately 30,000 sites that were amplified in all species 133 sites were identified with ambiguous inheritance, in that all trees implied more than one mutation at the same site. Closer examination of these sites has identified that they are the result of ancient polymorphisms that have subsequently undergone lineage sorting in the Bovini tribe, of which 53 have remained polymorphic since Bos and Bison species last shared a common ancestor with Bubalus between 5–8 million years ago (MYA. Conclusion Uncertainty arises in our phylogenetic reconstructions because many species in the Bovini diverged over a short period of time. It appears that a number of sites with ambiguous inheritance have been maintained in subsequent populations by chance (lineage sorting and that they have contributed to an association between Yak and Domestic cattle and an unreliable phylogenetic reconstruction for the Bison/Yak clade. Interestingly, a number of these

Phylogenetic reconstruction and the identification of ancient polymorphism in the Bovini tribe (Bovidae, Bovinae).

Science.gov (United States)

MacEachern, Sean; McEwan, John; Goddard, Mike

2009-04-24

The Bovinae subfamily incorporates an array of antelope, buffalo and cattle species. All of the members of this subfamily have diverged recently. Not surprisingly, a number of phylogenetic studies from molecular and morphological data have resulted in ambiguous trees and relationships amongst species, especially for Yak and Bison species. A partial phylogenetic reconstruction of 13 extant members of the Bovini tribe (Bovidae, Bovinae) from 15 complete or partially sequenced autosomal genes is presented. We identified 3 distinct lineages after the Bovini split from the Boselaphini and Tragelaphini tribes, which has lead to the (1) Buffalo clade (Bubalus and Syncerus species) and a more recent divergence leading to the (2) Banteng, Gaur and Mithan and (3) Domestic cattle clades. A fourth lineage may also exist that leads to Bison and Yak. However, there was some ambiguity as to whether this was a divergence from the Banteng/Gaur/Mithan or the Domestic cattle clade. From an analysis of approximately 30,000 sites that were amplified in all species 133 sites were identified with ambiguous inheritance, in that all trees implied more than one mutation at the same site. Closer examination of these sites has identified that they are the result of ancient polymorphisms that have subsequently undergone lineage sorting in the Bovini tribe, of which 53 have remained polymorphic since Bos and Bison species last shared a common ancestor with Bubalus between 5-8 million years ago (MYA). Uncertainty arises in our phylogenetic reconstructions because many species in the Bovini diverged over a short period of time. It appears that a number of sites with ambiguous inheritance have been maintained in subsequent populations by chance (lineage sorting) and that they have contributed to an association between Yak and Domestic cattle and an unreliable phylogenetic reconstruction for the Bison/Yak clade. Interestingly, a number of these aberrant sites are in coding sections of the genome

Side-by-side reading of PET and CT scans in oncology: Which patients might profit from integrated PET/CT?

International Nuclear Information System (INIS)

Reinartz, Patrick; Wieres, Franz-Josef; Schneider, Wolfram; Schur, Alexander; Buell, Ulrich

2004-01-01

Most early publications on integrated positron emission tomography/computed tomography (PET/CT) devices have reported the new scanner generation to be superior to conventional PET. However, few of these studies have analysed the situation where, in addition to PET, a current CT scan is available for side-by-side viewing. This fact is important, because combined PET/CT or a software-based fusion of the two modalities may improve diagnosis only in cases where side-by-side reading of PET and CT data does not lead to a definitive diagnosis. The aim of this study was to analyse which patients will profit from integrated PET/CT in terms of lesion characterization. A total of 328 consecutively admitted patients referred for PET in whom a current CT scan was available were included in the study. The localization of all pathological PET lesions, as well as possible infiltration of adjacent anatomical structures, was assessed. Of 467 pathological lesions, 94.0% were correctly assessed with respect to localization and infiltration by either conventional PET alone (51.6%) or combined reading of PET and the already existing CT scans (42.4%). Hence, in only 6.0% of all lesions, affecting 6.7% of all patients, could evaluation have profited from integrated PET/CT. We conclude that side-by-side viewing of PET and CT scans is essential, as in 42.4% of all cases, combined viewing was important for a correct diagnosis in our series. In up to 6.7% of patients, integrated PET/CT might have given additional information, so that in nearly 50% of patients some form of combined viewing of PET and CT data is needed for accurate lesion characterization. (orig.)

ADCK3, an ancestral kinase, is mutated in a form of recessive ataxia associated with coenzyme Q10 deficiency.

Science.gov (United States)

Lagier-Tourenne, Clotilde; Tazir, Meriem; López, Luis Carlos; Quinzii, Catarina M; Assoum, Mirna; Drouot, Nathalie; Busso, Cleverson; Makri, Samira; Ali-Pacha, Lamia; Benhassine, Traki; Anheim, Mathieu; Lynch, David R; Thibault, Christelle; Plewniak, Frédéric; Bianchetti, Laurent; Tranchant, Christine; Poch, Olivier; DiMauro, Salvatore; Mandel, Jean-Louis; Barros, Mario H; Hirano, Michio; Koenig, Michel

2008-03-01

Muscle coenzyme Q(10) (CoQ(10) or ubiquinone) deficiency has been identified in more than 20 patients with presumed autosomal-recessive ataxia. However, mutations in genes required for CoQ(10) biosynthetic pathway have been identified only in patients with infantile-onset multisystemic diseases or isolated nephropathy. Our SNP-based genome-wide scan in a large consanguineous family revealed a locus for autosomal-recessive ataxia at chromosome 1q41. The causative mutation is a homozygous splice-site mutation in the aarF-domain-containing kinase 3 gene (ADCK3). Five additional mutations in ADCK3 were found in three patients with sporadic ataxia, including one known to have CoQ(10) deficiency in muscle. All of the patients have childhood-onset cerebellar ataxia with slow progression, and three of six have mildly elevated lactate levels. ADCK3 is a mitochondrial protein homologous to the yeast COQ8 and the bacterial UbiB proteins, which are required for CoQ biosynthesis. Three out of four patients tested showed a low endogenous pool of CoQ(10) in their fibroblasts or lymphoblasts, and two out of three patients showed impaired ubiquinone synthesis, strongly suggesting that ADCK3 is also involved in CoQ(10) biosynthesis. The deleterious nature of the three identified missense changes was confirmed by the introduction of them at the corresponding positions of the yeast COQ8 gene. Finally, a phylogenetic analysis shows that ADCK3 belongs to the family of atypical kinases, which includes phosphoinositide and choline kinases, suggesting that ADCK3 plays an indirect regulatory role in ubiquinone biosynthesis possibly as part of a feedback loop that regulates ATP production.

Influence of radiation exposure rate on somatic mutation frequency and loss of reproductive integrity in tradescantia stamen hairs

International Nuclear Information System (INIS)

Ichikawa, S.; Nauman, C.H.; Sparrow, A.H.; Takahashi, C.S.

1978-01-01

Inflorescences of Tradescantia clone 02 (2n=12), hetero- or hemi-zygous for flower color, were exposed to a series of γ-ray exposures at two different exposure rates, 29.3 R/min and 0.026-0.52 R/min. Pink mutation-response curves, and survival curves based on reproductive integrity, were constructed for each of the exposure rates. Loss of reproductive integrity was also assessed at high (256 R/min) and low (0.52-4.17 R/min) γ-ray exposure rates in T. blossfeldiana (2n=72). All observations were made on stamen hairs. The higher exposure rate was 1.3-1.7 times more effective in inducing pink mutations in clone 02. A greater efficiency of the higher exposure rate was also found for both taxa at the loss of reproductive integrity endpoint. The D 0 values obtained at the higher exposure rates, 154 R for clone 02 and 720 R for T. blossfeldiana, were significantly lower than the corresponding values of 270 R and 1880 R obtained at the lower exposure rates. These D 0 's differ by factors of 1.75 and 2.61 for clone 02 and T. blossfeldiana, respectively. D 0 's for the two taxa were found to be inversely correlated with their interphase chromosome volumes. (Auth.)

Clonal architectures and driver mutations in metastatic melanomas.

Directory of Open Access Journals (Sweden)

Li Ding

Full Text Available To reveal the clonal architecture of melanoma and associated driver mutations, whole genome sequencing (WGS and targeted extension sequencing were used to characterize 124 melanoma cases. Significantly mutated gene analysis using 13 WGS cases and 15 additional paired extension cases identified known melanoma genes such as BRAF, NRAS, and CDKN2A, as well as a novel gene EPHA3, previously implicated in other cancer types. Extension studies using tumors from another 96 patients discovered a large number of truncation mutations in tumor suppressors (TP53 and RB1, protein phosphatases (e.g., PTEN, PTPRB, PTPRD, and PTPRT, as well as chromatin remodeling genes (e.g., ASXL3, MLL2, and ARID2. Deep sequencing of mutations revealed subclones in the majority of metastatic tumors from 13 WGS cases. Validated mutations from 12 out of 13 WGS patients exhibited a predominant UV signature characterized by a high frequency of C->T transitions occurring at the 3' base of dipyrimidine sequences while one patient (MEL9 with a hypermutator phenotype lacked this signature. Strikingly, a subclonal mutation signature analysis revealed that the founding clone in MEL9 exhibited UV signature but the secondary clone did not, suggesting different mutational mechanisms for two clonal populations from the same tumor. Further analysis of four metastases from different geographic locations in 2 melanoma cases revealed phylogenetic relationships and highlighted the genetic alterations responsible for differential drug resistance among metastatic tumors. Our study suggests that clonal evaluation is crucial for understanding tumor etiology and drug resistance in melanoma.

Transforming phylogenetic networks: Moving beyond tree space

OpenAIRE

Huber, Katharina T.; Moulton, Vincent; Wu, Taoyang

2016-01-01

Phylogenetic networks are a generalization of phylogenetic trees that are used to represent reticulate evolution. Unrooted phylogenetic networks form a special class of such networks, which naturally generalize unrooted phylogenetic trees. In this paper we define two operations on unrooted phylogenetic networks, one of which is a generalization of the well-known nearest-neighbor interchange (NNI) operation on phylogenetic trees. We show that any unrooted phylogenetic network can be transforme...

Molecular Etiology of Hearing Impairment in Inner Mongolia: mutations in SLC26A4 gene and relevant phenotype analysis

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Wu Bailin

2008-11-01

Full Text Available Abstract Background The molecular etiology of hearing impairment in Chinese has not been thoroughly investigated. Study of GJB2 gene revealed that 30.4% of the patients with hearing loss in Inner Mongolia carried GJB2 mutations. The SLC26A4 gene mutations and relevant phenotype are analyzed in this study. Methods One hundred and thirty-five deaf patients were included. The coding exons of SLC26A4 gene were sequence analyzed in 111 patients, not including 22 patients carrying bi-allelic GJB2 mutations or one patient carrying a known GJB2 dominant mutation as well as one patient with mtDNA 1555A>G mutation. All patients with SLC26A4 mutations or variants were subjected to high resolution temporal bone CT scan and those with confirmed enlarged vestibular aqueduct and/or other inner ear malformation were then given further ultrasound scan of thyroid and thyroid hormone assays. Results Twenty-six patients (19.26%, 26/135 were found carrying SLC26A4 mutation. Among them, 17 patients with bi-allelic SLC26A4 mutations were all confirmed to have EVA or other inner ear malformation by CT scan. Nine patients were heterozygous for one SLC26A4 mutation, including 3 confirmed to be EVA or EVA and Mondini dysplasia by CT scan. The most common mutation, IVS7-2A>G, accounted for 58.14% (25/43 of all SLC26A4 mutant alleles. The shape and function of thyroid were confirmed to be normal by thyroid ultrasound scan and thyroid hormone assays in 19 of the 20 patients with EVA or other inner ear malformation except one who had cystoid change in the right side of thyroid. No Pendred syndrome was diagnosed. Conclusion In Inner Mongolia, China, mutations in SLC26A4 gene account for about 12.6% (17/135 of the patients with hearing loss. Together with GJB2 (23/135, SLC26A4 are the two most commonly mutated genes causing deafness in this region. Pendred syndrome is not detected in this deaf population. We established a new strategy that detects SLC26A4 mutations prior to the

Molecular Etiology of Hearing Impairment in Inner Mongolia: mutations in SLC26A4 gene and relevant phenotype analysis

Science.gov (United States)

Dai, Pu; Yuan, Yongyi; Huang, Deliang; Zhu, Xiuhui; Yu, Fei; Kang, Dongyang; Yuan, Huijun; Wu, Bailin; Han, Dongyi; Wong, Lee-Jun C

2008-01-01

Background The molecular etiology of hearing impairment in Chinese has not been thoroughly investigated. Study of GJB2 gene revealed that 30.4% of the patients with hearing loss in Inner Mongolia carried GJB2 mutations. The SLC26A4 gene mutations and relevant phenotype are analyzed in this study. Methods One hundred and thirty-five deaf patients were included. The coding exons of SLC26A4 gene were sequence analyzed in 111 patients, not including 22 patients carrying bi-allelic GJB2 mutations or one patient carrying a known GJB2 dominant mutation as well as one patient with mtDNA 1555A>G mutation. All patients with SLC26A4 mutations or variants were subjected to high resolution temporal bone CT scan and those with confirmed enlarged vestibular aqueduct and/or other inner ear malformation were then given further ultrasound scan of thyroid and thyroid hormone assays. Results Twenty-six patients (19.26%, 26/135) were found carrying SLC26A4 mutation. Among them, 17 patients with bi-allelic SLC26A4 mutations were all confirmed to have EVA or other inner ear malformation by CT scan. Nine patients were heterozygous for one SLC26A4 mutation, including 3 confirmed to be EVA or EVA and Mondini dysplasia by CT scan. The most common mutation, IVS7-2A>G, accounted for 58.14% (25/43) of all SLC26A4 mutant alleles. The shape and function of thyroid were confirmed to be normal by thyroid ultrasound scan and thyroid hormone assays in 19 of the 20 patients with EVA or other inner ear malformation except one who had cystoid change in the right side of thyroid. No Pendred syndrome was diagnosed. Conclusion In Inner Mongolia, China, mutations in SLC26A4 gene account for about 12.6% (17/135) of the patients with hearing loss. Together with GJB2 (23/135), SLC26A4 are the two most commonly mutated genes causing deafness in this region. Pendred syndrome is not detected in this deaf population. We established a new strategy that detects SLC26A4 mutations prior to the temporal bone CT scan to

SWPhylo - A Novel Tool for Phylogenomic Inferences by Comparison of Oligonucleotide Patterns and Integration of Genome-Based and Gene-Based Phylogenetic Trees.

Science.gov (United States)

Yu, Xiaoyu; Reva, Oleg N

2018-01-01

Modern phylogenetic studies may benefit from the analysis of complete genome sequences of various microorganisms. Evolutionary inferences based on genome-scale analysis are believed to be more accurate than the gene-based alternative. However, the computational complexity of current phylogenomic procedures, inappropriateness of standard phylogenetic tools to process genome-wide data, and lack of reliable substitution models which correlates with alignment-free phylogenomic approaches deter microbiologists from using these opportunities. For example, the super-matrix and super-tree approaches of phylogenomics use multiple integrated genomic loci or individual gene-based trees to infer an overall consensus tree. However, these approaches potentially multiply errors of gene annotation and sequence alignment not mentioning the computational complexity and laboriousness of the methods. In this article, we demonstrate that the annotation- and alignment-free comparison of genome-wide tetranucleotide frequencies, termed oligonucleotide usage patterns (OUPs), allowed a fast and reliable inference of phylogenetic trees. These were congruent to the corresponding whole genome super-matrix trees in terms of tree topology when compared with other known approaches including 16S ribosomal RNA and GyrA protein sequence comparison, complete genome-based MAUVE, and CVTree methods. A Web-based program to perform the alignment-free OUP-based phylogenomic inferences was implemented at http://swphylo.bi.up.ac.za/. Applicability of the tool was tested on different taxa from subspecies to intergeneric levels. Distinguishing between closely related taxonomic units may be enforced by providing the program with alignments of marker protein sequences, eg, GyrA.

Keeping All the PIECES: Phylogenetically Informed Ex Situ Conservation of Endangered Species.

Science.gov (United States)

Larkin, Daniel J; Jacobi, Sarah K; Hipp, Andrew L; Kramer, Andrea T

2016-01-01

Ex situ conservation in germplasm and living collections is a major focus of global plant conservation strategies. Prioritizing species for ex situ collection is a necessary component of this effort for which sound strategies are needed. Phylogenetic considerations can play an important role in prioritization. Collections that are more phylogenetically diverse are likely to encompass more ecological and trait variation, and thus provide stronger conservation insurance and richer resources for future restoration efforts. However, phylogenetic criteria need to be weighed against other, potentially competing objectives. We used ex situ collection and threat rank data for North American angiosperms to investigate gaps in ex situ coverage and phylogenetic diversity of collections and to develop a flexible framework for prioritizing species across multiple objectives. We found that ex situ coverage of 18,766 North American angiosperm taxa was low with respect to the most vulnerable taxa: just 43% of vulnerable to critically imperiled taxa were in ex situ collections, far short of a year-2020 goal of 75%. In addition, species held in ex situ collections were phylogenetically clustered (P species been drawn at random. These patterns support incorporating phylogenetic considerations into ex situ prioritization in a manner balanced with other criteria, such as vulnerability. To meet this need, we present the 'PIECES' index (Phylogenetically Informed Ex situ Conservation of Endangered Species). PIECES integrates phylogenetic considerations into a flexible framework for prioritizing species across competing objectives using multi-criteria decision analysis. Applying PIECES to prioritizing ex situ conservation of North American angiosperms, we show strong return on investment across multiple objectives, some of which are negatively correlated with each other. A spreadsheet-based decision support tool for North American angiosperms is provided; this tool can be customized to

On Nakhleh's metric for reduced phylogenetic networks

OpenAIRE

Cardona, Gabriel; Llabrés, Mercè; Rosselló, Francesc; Valiente Feruglio, Gabriel Alejandro

2009-01-01

We prove that Nakhleh’s metric for reduced phylogenetic networks is also a metric on the classes of tree-child phylogenetic networks, semibinary tree-sibling time consistent phylogenetic networks, and multilabeled phylogenetic trees. We also prove that it separates distinguishable phylogenetic networks. In this way, it becomes the strongest dissimilarity measure for phylogenetic networks available so far. Furthermore, we propose a generalization of that metric that separates arbitrary phyl...

Phylogenetic Analysis Using Protein Mass Spectrometry.

Science.gov (United States)

Ma, Shiyong; Downard, Kevin M; Wong, Jason W H

2017-01-01

Through advances in molecular biology, comparative analysis of DNA sequences is currently the cornerstone in the study of molecular evolution and phylogenetics. Nevertheless, protein mass spectrometry offers some unique opportunities to enable phylogenetic analyses in organisms where DNA may be difficult or costly to obtain. To date, the methods of phylogenetic analysis using protein mass spectrometry can be classified into three categories: (1) de novo protein sequencing followed by classical phylogenetic reconstruction, (2) direct phylogenetic reconstruction using proteolytic peptide mass maps, and (3) mapping of mass spectral data onto classical phylogenetic trees. In this chapter, we provide a brief description of the three methods and the protocol for each method along with relevant tools and algorithms.

Integrative proteomics, genomics, and translational immunology approaches reveal mutated forms of Proteolipid Protein 1 (PLP1) and mutant-specific immune response in multiple sclerosis.

Science.gov (United States)

Qendro, Veneta; Bugos, Grace A; Lundgren, Debbie H; Glynn, John; Han, May H; Han, David K

2017-03-01

In order to gain mechanistic insights into multiple sclerosis (MS) pathogenesis, we utilized a multi-dimensional approach to test the hypothesis that mutations in myelin proteins lead to immune activation and central nervous system autoimmunity in MS. Mass spectrometry-based proteomic analysis of human MS brain lesions revealed seven unique mutations of PLP1; a key myelin protein that is known to be destroyed in MS. Surprisingly, in-depth genomic analysis of two MS patients at the genomic DNA and mRNA confirmed mutated PLP1 in RNA, but not in the genomic DNA. Quantification of wild type and mutant PLP RNA levels by qPCR further validated the presence of mutant PLP RNA in the MS patients. To seek evidence linking mutations in abundant myelin proteins and immune-mediated destruction of myelin, specific immune response against mutant PLP1 in MS patients was examined. Thus, we have designed paired, wild type and mutant peptide microarrays, and examined antibody response to multiple mutated PLP1 in sera from MS patients. Consistent with the idea of different patients exhibiting unique mutation profiles, we found that 13 out of 20 MS patients showed antibody responses against specific but not against all the mutant-PLP1 peptides. Interestingly, we found mutant PLP-directed antibody response against specific mutant peptides in the sera of pre-MS controls. The results from integrative proteomic, genomic, and immune analyses reveal a possible mechanism of mutation-driven pathogenesis in human MS. The study also highlights the need for integrative genomic and proteomic analyses for uncovering pathogenic mechanisms of human diseases. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Scanning device for a spectrometer

International Nuclear Information System (INIS)

Ignat'ev, V.M.

1982-01-01

The invention belongs to scanning devices and is intended for spectrum scanning in spectral devices. The purpose of the invention is broadening of spectral scanning range. The device construction ensures the spectrum scanning range determined from revolution fractions to several revolutions of the monochromator drum head, any number of the drum head revolutions determined by integral number with addition of the drum revolution fractions with high degree of accuracy being possible

Transforming phylogenetic networks: Moving beyond tree space.

Science.gov (United States)

Huber, Katharina T; Moulton, Vincent; Wu, Taoyang

2016-09-07

Phylogenetic networks are a generalization of phylogenetic trees that are used to represent reticulate evolution. Unrooted phylogenetic networks form a special class of such networks, which naturally generalize unrooted phylogenetic trees. In this paper we define two operations on unrooted phylogenetic networks, one of which is a generalization of the well-known nearest-neighbor interchange (NNI) operation on phylogenetic trees. We show that any unrooted phylogenetic network can be transformed into any other such network using only these operations. This generalizes the well-known fact that any phylogenetic tree can be transformed into any other such tree using only NNI operations. It also allows us to define a generalization of tree space and to define some new metrics on unrooted phylogenetic networks. To prove our main results, we employ some fascinating new connections between phylogenetic networks and cubic graphs that we have recently discovered. Our results should be useful in developing new strategies to search for optimal phylogenetic networks, a topic that has recently generated some interest in the literature, as well as for providing new ways to compare networks. Copyright © 2016 Elsevier Ltd. All rights reserved.

Scanning capacitance microscope as a tool for the characterization of integrated circuits

Science.gov (United States)

Born, A.; Wiesendanger, R.

With the decreasing size of integrated circuits (ICs), there is an increasing demand for the measurement of doping profiles with high spatial resolution. The scanning capacitance microscope (SCM) offers the possibility of measuring 2D dopant profiles with spatial resolution of less than 20 nm. A great problem of the SCM technique is the influence of previous measurements on subsequent ones. We have observed hysteresis in the SCM images and measured low-frequency C-V curves with high-frequency equipment. A theoretical model was developed to understand this phenomenon. We are now undertaking the first steps using the SCM as a standard device for the characterization of ICs.

Cross-Neutralising Nanobodies Bind to a Conserved Pocket in the Hemagglutinin Stem Region Identified Using Yeast Display and Deep Mutational Scanning.

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Tiziano Gaiotto

Full Text Available Cross-neutralising monoclonal antibodies against influenza hemagglutinin (HA are of considerable interest as both therapeutics and diagnostic tools. We have recently described five different single domain antibodies (nanobodies which share this cross-neutralising activity and suggest their small size, high stability, and cleft binding properties may present distinct advantages over equivalent conventional antibodies. We have used yeast display in combination with deep mutational scanning to give residue level resolution of positions in the antibody-HA interface which are crucial for binding. In addition, we have mapped positions within HA predicted to have minimal effect on antibody binding when mutated. Our cross-neutralising nanobodies were shown to bind to a highly conserved pocket in the HA2 domain of A(H1N1pdm09 influenza virus overlapping with the fusion peptide suggesting their mechanism of action is through the inhibition of viral membrane fusion. We also note that the epitope overlaps with that of CR6261 and F10 which are human monoclonal antibodies in clinical development as immunotherapeutics. Although all five nanobodies mapped to the same highly conserved binding pocket we observed differences in the size of the epitope footprint which has implications in comparing the relative genetic barrier each nanobody presents to a rapidly evolving influenza virus. To further refine our epitope map, we have re-created naturally occurring mutations within this HA stem epitope and tested their effect on binding using yeast display. We have shown that a D46N mutation in the HA2 stem domain uniquely interferes with binding of R2b-E8. Further testing of this substitution in the context of full length purified HA from 1918 H1N1 pandemic (Spanish flu, 2009 H1N1 pandemic (swine flu and highly pathogenic avian influenza H5N1 demonstrated binding which correlated with D46 whereas binding to seasonal H1N1 strains carrying N46 was absent. In addition, our

The RNA recognition motif of eukaryotic translation initiation factor 3g (eIF3g) is required for resumption of scanning of posttermination ribosomes for reinitiation on GCN4 and together with eIF3i stimulates linear scanning.

Science.gov (United States)

Cuchalová, Lucie; Kouba, Tomás; Herrmannová, Anna; Dányi, István; Chiu, Wen-Ling; Valásek, Leos

2010-10-01

Recent reports have begun unraveling the details of various roles of individual eukaryotic translation initiation factor 3 (eIF3) subunits in translation initiation. Here we describe functional characterization of two essential Saccharomyces cerevisiae eIF3 subunits, g/Tif35 and i/Tif34, previously suggested to be dispensable for formation of the 48S preinitiation complexes (PICs) in vitro. A triple-Ala substitution of conserved residues in the RRM of g/Tif35 (g/tif35-KLF) or a single-point mutation in the WD40 repeat 6 of i/Tif34 (i/tif34-Q258R) produces severe growth defects and decreases the rate of translation initiation in vivo without affecting the integrity of eIF3 and formation of the 43S PICs in vivo. Both mutations also diminish induction of GCN4 expression, which occurs upon starvation via reinitiation. Whereas g/tif35-KLF impedes resumption of scanning for downstream reinitiation by 40S ribosomes terminating at upstream open reading frame 1 (uORF1) in the GCN4 mRNA leader, i/tif34-Q258R prevents full GCN4 derepression by impairing the rate of scanning of posttermination 40S ribosomes moving downstream from uORF1. In addition, g/tif35-KLF reduces processivity of scanning through stable secondary structures, and g/Tif35 specifically interacts with Rps3 and Rps20 located near the ribosomal mRNA entry channel. Together these results implicate g/Tif35 and i/Tif34 in stimulation of linear scanning and, specifically in the case of g/Tif35, also in proper regulation of the GCN4 reinitiation mechanism.

SWPhylo – A Novel Tool for Phylogenomic Inferences by Comparison of Oligonucleotide Patterns and Integration of Genome-Based and Gene-Based Phylogenetic Trees

Science.gov (United States)

Yu, Xiaoyu; Reva, Oleg N

2018-01-01

Modern phylogenetic studies may benefit from the analysis of complete genome sequences of various microorganisms. Evolutionary inferences based on genome-scale analysis are believed to be more accurate than the gene-based alternative. However, the computational complexity of current phylogenomic procedures, inappropriateness of standard phylogenetic tools to process genome-wide data, and lack of reliable substitution models which correlates with alignment-free phylogenomic approaches deter microbiologists from using these opportunities. For example, the super-matrix and super-tree approaches of phylogenomics use multiple integrated genomic loci or individual gene-based trees to infer an overall consensus tree. However, these approaches potentially multiply errors of gene annotation and sequence alignment not mentioning the computational complexity and laboriousness of the methods. In this article, we demonstrate that the annotation- and alignment-free comparison of genome-wide tetranucleotide frequencies, termed oligonucleotide usage patterns (OUPs), allowed a fast and reliable inference of phylogenetic trees. These were congruent to the corresponding whole genome super-matrix trees in terms of tree topology when compared with other known approaches including 16S ribosomal RNA and GyrA protein sequence comparison, complete genome-based MAUVE, and CVTree methods. A Web-based program to perform the alignment-free OUP-based phylogenomic inferences was implemented at http://swphylo.bi.up.ac.za/. Applicability of the tool was tested on different taxa from subspecies to intergeneric levels. Distinguishing between closely related taxonomic units may be enforced by providing the program with alignments of marker protein sequences, eg, GyrA. PMID:29511354

A format for phylogenetic placements.

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Frederick A Matsen

Full Text Available We have developed a unified format for phylogenetic placements, that is, mappings of environmental sequence data (e.g., short reads into a phylogenetic tree. We are motivated to do so by the growing number of tools for computing and post-processing phylogenetic placements, and the lack of an established standard for storing them. The format is lightweight, versatile, extensible, and is based on the JSON format, which can be parsed by most modern programming languages. Our format is already implemented in several tools for computing and post-processing parsimony- and likelihood-based phylogenetic placements and has worked well in practice. We believe that establishing a standard format for analyzing read placements at this early stage will lead to a more efficient development of powerful and portable post-analysis tools for the growing applications of phylogenetic placement.

PhyloBot: A Web Portal for Automated Phylogenetics, Ancestral Sequence Reconstruction, and Exploration of Mutational Trajectories.

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Victor Hanson-Smith

2016-07-01

Full Text Available The method of phylogenetic ancestral sequence reconstruction is a powerful approach for studying evolutionary relationships among protein sequence, structure, and function. In particular, this approach allows investigators to (1 reconstruct and "resurrect" (that is, synthesize in vivo or in vitro extinct proteins to study how they differ from modern proteins, (2 identify key amino acid changes that, over evolutionary timescales, have altered the function of the protein, and (3 order historical events in the evolution of protein function. Widespread use of this approach has been slow among molecular biologists, in part because the methods require significant computational expertise. Here we present PhyloBot, a web-based software tool that makes ancestral sequence reconstruction easy. Designed for non-experts, it integrates all the necessary software into a single user interface. Additionally, PhyloBot provides interactive tools to explore evolutionary trajectories between ancestors, enabling the rapid generation of hypotheses that can be tested using genetic or biochemical approaches. Early versions of this software were used in previous studies to discover genetic mechanisms underlying the functions of diverse protein families, including V-ATPase ion pumps, DNA-binding transcription regulators, and serine/threonine protein kinases. PhyloBot runs in a web browser, and is available at the following URL: http://www.phylobot.com. The software is implemented in Python using the Django web framework, and runs on elastic cloud computing resources from Amazon Web Services. Users can create and submit jobs on our free server (at the URL listed above, or use our open-source code to launch their own PhyloBot server.

Phylogenetic inertia and Darwin's higher law.

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Shanahan, Timothy

2011-03-01

The concept of 'phylogenetic inertia' is routinely deployed in evolutionary biology as an alternative to natural selection for explaining the persistence of characteristics that appear sub-optimal from an adaptationist perspective. However, in many of these contexts the precise meaning of 'phylogenetic inertia' and its relationship to selection are far from clear. After tracing the history of the concept of 'inertia' in evolutionary biology, I argue that treating phylogenetic inertia and natural selection as alternative explanations is mistaken because phylogenetic inertia is, from a Darwinian point of view, simply an expected effect of selection. Although Darwin did not discuss 'phylogenetic inertia,' he did assert the explanatory priority of selection over descent. An analysis of 'phylogenetic inertia' provides a perspective from which to assess Darwin's view. Copyright © 2010 Elsevier Ltd. All rights reserved.

A Consistent Phylogenetic Backbone for the Fungi

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Ebersberger, Ingo; de Matos Simoes, Ricardo; Kupczok, Anne; Gube, Matthias; Kothe, Erika; Voigt, Kerstin; von Haeseler, Arndt

2012-01-01

The kingdom of fungi provides model organisms for biotechnology, cell biology, genetics, and life sciences in general. Only when their phylogenetic relationships are stably resolved, can individual results from fungal research be integrated into a holistic picture of biology. However, and despite recent progress, many deep relationships within the fungi remain unclear. Here, we present the first phylogenomic study of an entire eukaryotic kingdom that uses a consistency criterion to strengthen phylogenetic conclusions. We reason that branches (splits) recovered with independent data and different tree reconstruction methods are likely to reflect true evolutionary relationships. Two complementary phylogenomic data sets based on 99 fungal genomes and 109 fungal expressed sequence tag (EST) sets analyzed with four different tree reconstruction methods shed light from different angles on the fungal tree of life. Eleven additional data sets address specifically the phylogenetic position of Blastocladiomycota, Ustilaginomycotina, and Dothideomycetes, respectively. The combined evidence from the resulting trees supports the deep-level stability of the fungal groups toward a comprehensive natural system of the fungi. In addition, our analysis reveals methodologically interesting aspects. Enrichment for EST encoded data—a common practice in phylogenomic analyses—introduces a strong bias toward slowly evolving and functionally correlated genes. Consequently, the generalization of phylogenomic data sets as collections of randomly selected genes cannot be taken for granted. A thorough characterization of the data to assess possible influences on the tree reconstruction should therefore become a standard in phylogenomic analyses. PMID:22114356

Integrating Airborne and Terrestrial Laser Scanning data to monitor active landsliding

Science.gov (United States)

Székely, B.; Molnár, G.; Roncat, A.; Lehner, H.; Gaisecker, Th.; Drexel, P.

2009-04-01

Active slope processes often endanger various built-up objects and, as a consequence, sometimes human lives as well. Data acquision on the status and evolution of such slopes, especially those that had already affected by landsliding, therefore is a primary target for engineering geomorphic research. The method of laser scanning provides an appropriate data collection technique with the requested accuracy. Data from repeated Airborne Laser Scanning (ALS) campaigns are suitable to be analysed for the slow, incipient movements of the slope. The problem of this surveying technique is that repetition time is strongly dependent on the financial resources of the monitoring project, and often the requested recurrence of flight campaigns cannot be achieved. A possible solution to densify the data acquisition in time is the application of Terrestrial Laser Scanning (TLS) and intergration of its data with ALS data sets. TLS has the advantage of flexibility and shorter observation distances compared to ALS. This technique needs special considerations and tedious processing since the geometric setting of the data acquision considerably differ in TLS and ALS. Furthermore, obstacles in the landscape may partly hamper the data acqusition which rarely the case in ALS. Our case study area is a several-decade-long active landsliding in Doren (Federal State Vorarlberg, Austria) that as it develops, it is about to endangers houses of the locality. The site is especially suitable for the project, because multi-temporal data sets (from ALS flight campaigns in 2003, 2006 and 2007, respectively) of this area are available. The data integration is carried out in the form of production of point clouds (sensed from various points of the valley sides) and we compared the results with the results of the previous ALS campaigns. With the planned repetition of the TLS measurements new and detailed insights can be achieved concerning the evolution of the incipient and on-going slow motions. This

Mutation Rate Variation is a Primary Determinant of the Distribution of Allele Frequencies in Humans.

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Arbel Harpak

2016-12-01

Full Text Available The site frequency spectrum (SFS has long been used to study demographic history and natural selection. Here, we extend this summary by examining the SFS conditional on the alleles found at the same site in other species. We refer to this extension as the "phylogenetically-conditioned SFS" or cSFS. Using recent large-sample data from the Exome Aggregation Consortium (ExAC, combined with primate genome sequences, we find that human variants that occurred independently in closely related primate lineages are at higher frequencies in humans than variants with parallel substitutions in more distant primates. We show that this effect is largely due to sites with elevated mutation rates causing significant departures from the widely-used infinite sites mutation model. Our analysis also suggests substantial variation in mutation rates even among mutations involving the same nucleotide changes. In summary, we show that variable mutation rates are key determinants of the SFS in humans.

The transposition distance for phylogenetic trees

OpenAIRE

Rossello, Francesc; Valiente, Gabriel

2006-01-01

The search for similarity and dissimilarity measures on phylogenetic trees has been motivated by the computation of consensus trees, the search by similarity in phylogenetic databases, and the assessment of clustering results in bioinformatics. The transposition distance for fully resolved phylogenetic trees is a recent addition to the extensive collection of available metrics for comparing phylogenetic trees. In this paper, we generalize the transposition distance from fully resolved to arbi...

A de novo deletion mutation in SOX10 in a Chinese family with Waardenburg syndrome type 4.

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Wang, Xiong; Zhu, Yaowu; Shen, Na; Peng, Jing; Wang, Chunyu; Liu, Haiyi; Lu, Yanjun

2017-01-27

Waardenburg syndrome type 4 (WS4) or Waardenburg-Shah syndrome is a rare genetic disorder with a prevalence of <1/1,000,000 and characterized by the association of congenital sensorineural hearing loss, pigmentary abnormalities, and intestinal aganglionosis. There are three types of WS4 (WS4A-C) caused by mutations in endothelin receptor type B, endothelin 3, and SRY-box 10 (SOX10), respectively. This study investigated a genetic mutation in a Chinese family with one WS4 patient in order to improve genetic counselling. Genomic DNA was extracted, and mutation analysis of the three WS4 related genes was performed using Sanger sequencing. We detected a de novo heterozygous deletion mutation [c.1333delT (p.Ser445Glnfs*57)] in SOX10 in the patient; however, this mutation was absent in the unaffected parents and 40 ethnicity matched healthy controls. Subsequent phylogenetic analysis and three-dimensional modelling of the SOX10 protein confirmed that the c.1333delT heterozygous mutation was pathogenic, indicating that this mutation might constitute a candidate disease-causing mutation.

Phylogenetic Trees From Sequences

Science.gov (United States)

Ryvkin, Paul; Wang, Li-San

In this chapter, we review important concepts and approaches for phylogeny reconstruction from sequence data.We first cover some basic definitions and properties of phylogenetics, and briefly explain how scientists model sequence evolution and measure sequence divergence. We then discuss three major approaches for phylogenetic reconstruction: distance-based phylogenetic reconstruction, maximum parsimony, and maximum likelihood. In the third part of the chapter, we review how multiple phylogenies are compared by consensus methods and how to assess confidence using bootstrapping. At the end of the chapter are two sections that list popular software packages and additional reading.

RB1 mutation spectrum in a comprehensive nationwide cohort of retinoblastoma patients

NARCIS (Netherlands)

Dommering, Charlotte J.; Mol, Berber M.; Moll, Annette C.; Burton, Margaret; Cloos, Jacqueline; Dorsman, Josephine C.; Meijers-Heijboer, Hanne; van der Hout, Annemarie H.

Background Retinoblastoma (Rb) is a childhood cancer of the retina, commonly initiated by biallelic inactivation of the RB1 gene. Knowledge of the presence of a heritable RB1 mutation can help in risk management and reproductive decision making. We report here on RB1 mutation scanning in a unique

Prevalence of drug resistance mutations and non-B subtypes in newly diagnosed HIV-1 patients in Denmark

DEFF Research Database (Denmark)

Jørgensen, Louise B; Christensen, Marianne B; Gerstoft, Jan

2003-01-01

The aim of this study was to monitor the prevalence of drug resistance mutations in newly diagnosed HIV-1 positive individuals in Denmark. In addition we assessed the prevalence of non-B subtypes based on phylogenetic analysis of the pol gene. Plasma samples from 104 newly diagnosed HIV-1 positive...... patients were obtained in the year 2000. The entire protease gene and 320 amino acids of the reverse transcriptase gene were genotyped. Sequences were obtained from 97 patients. No subjects displayed primary resistance mutations in the protease gene, whereas all carried 1 or more secondary mutations....... Resistance mutations in the RT-gene associated with NRTI-resistance were found in 1 patient, who was infected with zidovudine resistant HIV-1 harbouring the M41L mutation in combination with T215S and L210S. The T215S mutation has been showed to be associated with reversion of zidovudine resistance. The T215...

A novel nonsense mutation in the NDP gene in a Chinese family with Norrie disease.

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Liu, Deyuan; Hu, Zhengmao; Peng, Yu; Yu, Changhong; Liu, Yalan; Mo, Xiaoyun; Li, Xiaoping; Lu, Lina; Xu, Xiaojuan; Su, Wei; Pan, Qian; Xia, Kun

2010-12-08

Norrie disease (ND), a rare X-linked recessive disorder, is characterized by congenital blindness and, occasionally, mental retardation and hearing loss. ND is caused by the Norrie Disease Protein gene (NDP), which codes for norrin, a cysteine-rich protein involved in ocular vascular development. Here, we report a novel mutation of NDP that was identified in a Chinese family in which three members displayed typical ND symptoms and other complex phenotypes, such as cerebellar atrophy, motor disorders, and mental disorders. We conducted an extensive clinical examination of the proband and performed a computed tomography (CT) scan of his brain. Additionally, we performed ophthalmic examinations, haplotype analyses, and NDP DNA sequencing for 26 individuals from the proband's extended family. The proband's computed tomography scan, in which the fifth ventricle could be observed, indicated cerebellar atrophy. Genome scans and haplotype analyses traced the disease to chromosome Xp21.1-p11.22. Mutation screening of the NDP gene identified a novel nonsense mutation, c.343C>T, in this region. Although recent research has shown that multiple different mutations can be responsible for the ND phenotype, additional research is needed to understand the mechanism responsible for the diverse phenotypes caused by mutations in the NDP gene.

Self-sensing cantilevers with integrated conductive coaxial tips for high-resolution electrical scanning probe metrology

International Nuclear Information System (INIS)

Haemmerli, Alexandre J.; Pruitt, Beth L.; Harjee, Nahid; Koenig, Markus; Garcia, Andrei G. F.; Goldhaber-Gordon, David

2015-01-01

The lateral resolution of many electrical scanning probe techniques is limited by the spatial extent of the electrostatic potential profiles produced by their probes. Conventional unshielded conductive atomic force microscopy probes produce broad potential profiles. Shielded probes could offer higher resolution and easier data interpretation in the study of nanostructures. Electrical scanning probe techniques require a method of locating structures of interest, often by mapping surface topography. As the samples studied with these techniques are often photosensitive, the typical laser measurement of cantilever deflection can excite the sample, causing undesirable changes electrical properties. In this work, we present the design, fabrication, and characterization of probes that integrate coaxial tips for spatially sharp potential profiles with piezoresistors for self-contained, electrical displacement sensing. With the apex 100 nm above the sample surface, the electrostatic potential profile produced by our coaxial tips is more than 2 times narrower than that of unshielded tips with no long tails. In a scan bandwidth of 1 Hz–10 kHz, our probes have a displacement resolution of 2.9 Å at 293 K and 79 Å at 2 K, where the low-temperature performance is limited by amplifier noise. We show scanning gate microscopy images of a quantum point contact obtained with our probes, highlighting the improvement to lateral resolution resulting from the coaxial tip

Integrated genomic classification of melanocytic tumors of the central nervous system using mutation analysis, copy number alterations and DNA methylation profiling.

Science.gov (United States)

Griewank, Klaus; Koelsche, Christian; van de Nes, Johannes A P; Schrimpf, Daniel; Gessi, Marco; Möller, Inga; Sucker, Antje; Scolyer, Richard A; Buckland, Michael E; Murali, Rajmohan; Pietsch, Torsten; von Deimling, Andreas; Schadendorf, Dirk

2018-06-11

In the central nervous system, distinguishing primary leptomeningeal melanocytic tumors from melanoma metastases and predicting their biological behavior solely using histopathologic criteria can be challenging. We aimed to assess the diagnostic and prognostic value of integrated molecular analysis. Targeted next-generation-sequencing, array-based genome-wide methylation analysis and BAP1 immunohistochemistry was performed on the largest cohort of central nervous system melanocytic tumors analyzed to date, incl. 47 primary tumors of the central nervous system, 16 uveal melanomas. 13 cutaneous melanoma metastasis and 2 blue nevus-like melanomas. Gene mutation, DNA-methylation and copy-number profiles were correlated with clinicopathological features. Combining mutation, copy-number and DNA-methylation profiles clearly distinguished cutaneous melanoma metastases from other melanocytic tumors. Primary leptomeningeal melanocytic tumors, uveal melanomas and blue nevus-like melanoma showed common DNA-methylation, copy-number alteration and gene mutation signatures. Notably, tumors demonstrating chromosome 3 monosomy and BAP1 alterations formed a homogeneous subset within this group. Integrated molecular profiling aids in distinguishing primary from metastatic melanocytic tumors of the central nervous system. Primary leptomeningeal melanocytic tumors, uveal melanoma and blue nevus-like melanoma share molecular similarity with chromosome 3 and BAP1 alterations markers of poor prognosis. Copyright ©2018, American Association for Cancer Research.

Locating a tree in a phylogenetic network

NARCIS (Netherlands)

Iersel, van L.J.J.; Semple, C.; Steel, M.A.

2010-01-01

Phylogenetic trees and networks are leaf-labelled graphs that are used to describe evolutionary histories of species. The Tree Containment problem asks whether a given phylogenetic tree is embedded in a given phylogenetic network. Given a phylogenetic network and a cluster of species, the Cluster

Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder

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Atsushi Takata

2018-01-01

Full Text Available Recent studies have established important roles of de novo mutations (DNMs in autism spectrum disorders (ASDs. Here, we analyze DNMs in 262 ASD probands of Japanese origin and confirm the “de novo paradigm” of ASDs across ethnicities. Based on this consistency, we combine the lists of damaging DNMs in our and published ASD cohorts (total number of trios, 4,244 and perform integrative bioinformatics analyses. Besides replicating the findings of previous studies, our analyses highlight ATP-binding genes and fetal cerebellar/striatal circuits. Analysis of individual genes identified 61 genes enriched for damaging DNMs, including ten genes for which our dataset now contributes to statistical significance. Screening of compounds altering the expression of genes hit by damaging DNMs reveals a global downregulating effect of valproic acid, a known risk factor for ASDs, whereas cardiac glycosides upregulate these genes. Collectively, our integrative approach provides deeper biological and potential medical insights into ASDs.

Molecular Phylogenetics: Concepts for a Newcomer.

Science.gov (United States)

Ajawatanawong, Pravech

Molecular phylogenetics is the study of evolutionary relationships among organisms using molecular sequence data. The aim of this review is to introduce the important terminology and general concepts of tree reconstruction to biologists who lack a strong background in the field of molecular evolution. Some modern phylogenetic programs are easy to use because of their user-friendly interfaces, but understanding the phylogenetic algorithms and substitution models, which are based on advanced statistics, is still important for the analysis and interpretation without a guide. Briefly, there are five general steps in carrying out a phylogenetic analysis: (1) sequence data preparation, (2) sequence alignment, (3) choosing a phylogenetic reconstruction method, (4) identification of the best tree, and (5) evaluating the tree. Concepts in this review enable biologists to grasp the basic ideas behind phylogenetic analysis and also help provide a sound basis for discussions with expert phylogeneticists.

phylo-node: A molecular phylogenetic toolkit using Node.js.

Science.gov (United States)

O'Halloran, Damien M

2017-01-01

Node.js is an open-source and cross-platform environment that provides a JavaScript codebase for back-end server-side applications. JavaScript has been used to develop very fast and user-friendly front-end tools for bioinformatic and phylogenetic analyses. However, no such toolkits are available using Node.js to conduct comprehensive molecular phylogenetic analysis. To address this problem, I have developed, phylo-node, which was developed using Node.js and provides a stable and scalable toolkit that allows the user to perform diverse molecular and phylogenetic tasks. phylo-node can execute the analysis and process the resulting outputs from a suite of software options that provides tools for read processing and genome alignment, sequence retrieval, multiple sequence alignment, primer design, evolutionary modeling, and phylogeny reconstruction. Furthermore, phylo-node enables the user to deploy server dependent applications, and also provides simple integration and interoperation with other Node modules and languages using Node inheritance patterns, and a customized piping module to support the production of diverse pipelines. phylo-node is open-source and freely available to all users without sign-up or login requirements. All source code and user guidelines are openly available at the GitHub repository: https://github.com/dohalloran/phylo-node.

MutAid: Sanger and NGS Based Integrated Pipeline for Mutation Identification, Validation and Annotation in Human Molecular Genetics.

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Ram Vinay Pandey

Full Text Available Traditional Sanger sequencing as well as Next-Generation Sequencing have been used for the identification of disease causing mutations in human molecular research. The majority of currently available tools are developed for research and explorative purposes and often do not provide a complete, efficient, one-stop solution. As the focus of currently developed tools is mainly on NGS data analysis, no integrative solution for the analysis of Sanger data is provided and consequently a one-stop solution to analyze reads from both sequencing platforms is not available. We have therefore developed a new pipeline called MutAid to analyze and interpret raw sequencing data produced by Sanger or several NGS sequencing platforms. It performs format conversion, base calling, quality trimming, filtering, read mapping, variant calling, variant annotation and analysis of Sanger and NGS data under a single platform. It is capable of analyzing reads from multiple patients in a single run to create a list of potential disease causing base substitutions as well as insertions and deletions. MutAid has been developed for expert and non-expert users and supports four sequencing platforms including Sanger, Illumina, 454 and Ion Torrent. Furthermore, for NGS data analysis, five read mappers including BWA, TMAP, Bowtie, Bowtie2 and GSNAP and four variant callers including GATK-HaplotypeCaller, SAMTOOLS, Freebayes and VarScan2 pipelines are supported. MutAid is freely available at https://sourceforge.net/projects/mutaid.

MutAid: Sanger and NGS Based Integrated Pipeline for Mutation Identification, Validation and Annotation in Human Molecular Genetics.

Science.gov (United States)

Pandey, Ram Vinay; Pabinger, Stephan; Kriegner, Albert; Weinhäusel, Andreas

2016-01-01

Traditional Sanger sequencing as well as Next-Generation Sequencing have been used for the identification of disease causing mutations in human molecular research. The majority of currently available tools are developed for research and explorative purposes and often do not provide a complete, efficient, one-stop solution. As the focus of currently developed tools is mainly on NGS data analysis, no integrative solution for the analysis of Sanger data is provided and consequently a one-stop solution to analyze reads from both sequencing platforms is not available. We have therefore developed a new pipeline called MutAid to analyze and interpret raw sequencing data produced by Sanger or several NGS sequencing platforms. It performs format conversion, base calling, quality trimming, filtering, read mapping, variant calling, variant annotation and analysis of Sanger and NGS data under a single platform. It is capable of analyzing reads from multiple patients in a single run to create a list of potential disease causing base substitutions as well as insertions and deletions. MutAid has been developed for expert and non-expert users and supports four sequencing platforms including Sanger, Illumina, 454 and Ion Torrent. Furthermore, for NGS data analysis, five read mappers including BWA, TMAP, Bowtie, Bowtie2 and GSNAP and four variant callers including GATK-HaplotypeCaller, SAMTOOLS, Freebayes and VarScan2 pipelines are supported. MutAid is freely available at https://sourceforge.net/projects/mutaid.

Locating a tree in a phylogenetic network

OpenAIRE

van Iersel, Leo; Semple, Charles; Steel, Mike

2010-01-01

Phylogenetic trees and networks are leaf-labelled graphs that are used to describe evolutionary histories of species. The Tree Containment problem asks whether a given phylogenetic tree is embedded in a given phylogenetic network. Given a phylogenetic network and a cluster of species, the Cluster Containment problem asks whether the given cluster is a cluster of some phylogenetic tree embedded in the network. Both problems are known to be NP-complete in general. In this article, we consider t...

Nonbinary tree-based phylogenetic networks

OpenAIRE

Jetten, Laura; van Iersel, Leo

2016-01-01

Rooted phylogenetic networks are used to describe evolutionary histories that contain non-treelike evolutionary events such as hybridization and horizontal gene transfer. In some cases, such histories can be described by a phylogenetic base-tree with additional linking arcs, which can for example represent gene transfer events. Such phylogenetic networks are called tree-based. Here, we consider two possible generalizations of this concept to nonbinary networks, which we call tree-based and st...

Encoding phylogenetic trees in terms of weighted quartets.

Science.gov (United States)

Grünewald, Stefan; Huber, Katharina T; Moulton, Vincent; Semple, Charles

2008-04-01

One of the main problems in phylogenetics is to develop systematic methods for constructing evolutionary or phylogenetic trees. For a set of species X, an edge-weighted phylogenetic X-tree or phylogenetic tree is a (graph theoretical) tree with leaf set X and no degree 2 vertices, together with a map assigning a non-negative length to each edge of the tree. Within phylogenetics, several methods have been proposed for constructing such trees that work by trying to piece together quartet trees on X, i.e. phylogenetic trees each having four leaves in X. Hence, it is of interest to characterise when a collection of quartet trees corresponds to a (unique) phylogenetic tree. Recently, Dress and Erdös provided such a characterisation for binary phylogenetic trees, that is, phylogenetic trees all of whose internal vertices have degree 3. Here we provide a new characterisation for arbitrary phylogenetic trees.

High mitochondrial mutation rates estimated from deep-rooting Costa Rican pedigrees

Science.gov (United States)

Madrigal, Lorena; Melendez-Obando, Mauricio; Villegas-Palma, Ramon; Barrantes, Ramiro; Raventos, Henrieta; Pereira, Reynaldo; Luiselli, Donata; Pettener, Davide; Barbujani, Guido

2012-01-01

Estimates of mutation rates for the noncoding hypervariable Region I (HVR-I) of mitochondrial DNA (mtDNA) vary widely, depending on whether they are inferred from phylogenies (assuming that molecular evolution is clock-like) or directly from pedigrees. All pedigree-based studies so far were conducted on populations of European origin. In this paper we analyzed 19 deep-rooting pedigrees in a population of mixed origin in Costa Rica. We calculated two estimates of the HVR-I mutation rate, one considering all apparent mutations, and one disregarding changes at sites known to be mutational hot spots and eliminating genealogy branches which might be suspected to include errors, or unrecognized adoptions along the female lines. At the end of this procedure, we still observed a mutation rate equal to 1.24 × 10−6, per site per year, i.e., at least three-fold as high as estimates derived from phylogenies. Our results confirm that mutation rates observed in pedigrees are much higher than estimated assuming a neutral model of long-term HVRI evolution. We argue that, until the cause of these discrepancies will be fully understood, both lower estimates (i.e., those derived from phylogenetic comparisons) and higher, direct estimates such as those obtained in this study, should be considered when modeling evolutionary and demographic processes. PMID:22460349

Global patterns of amphibian phylogenetic diversity

DEFF Research Database (Denmark)

Fritz, Susanne; Rahbek, Carsten

2012-01-01

Aim  Phylogenetic diversity can provide insight into how evolutionary processes may have shaped contemporary patterns of species richness. Here, we aim to test for the influence of phylogenetic history on global patterns of amphibian species richness, and to identify areas where macroevolutionary...... processes such as diversification and dispersal have left strong signatures on contemporary species richness. Location  Global; equal-area grid cells of approximately 10,000 km2. Methods  We generated an amphibian global supertree (6111 species) and repeated analyses with the largest available molecular...... phylogeny (2792 species). We combined each tree with global species distributions to map four indices of phylogenetic diversity. To investigate congruence between global spatial patterns of amphibian species richness and phylogenetic diversity, we selected Faith’s phylogenetic diversity (PD) index...

DRUMS: a human disease related unique gene mutation search engine.

Science.gov (United States)

Li, Zuofeng; Liu, Xingnan; Wen, Jingran; Xu, Ye; Zhao, Xin; Li, Xuan; Liu, Lei; Zhang, Xiaoyan

2011-10-01

With the completion of the human genome project and the development of new methods for gene variant detection, the integration of mutation data and its phenotypic consequences has become more important than ever. Among all available resources, locus-specific databases (LSDBs) curate one or more specific genes' mutation data along with high-quality phenotypes. Although some genotype-phenotype data from LSDB have been integrated into central databases little effort has been made to integrate all these data by a search engine approach. In this work, we have developed disease related unique gene mutation search engine (DRUMS), a search engine for human disease related unique gene mutation as a convenient tool for biologists or physicians to retrieve gene variant and related phenotype information. Gene variant and phenotype information were stored in a gene-centred relational database. Moreover, the relationships between mutations and diseases were indexed by the uniform resource identifier from LSDB, or another central database. By querying DRUMS, users can access the most popular mutation databases under one interface. DRUMS could be treated as a domain specific search engine. By using web crawling, indexing, and searching technologies, it provides a competitively efficient interface for searching and retrieving mutation data and their relationships to diseases. The present system is freely accessible at http://www.scbit.org/glif/new/drums/index.html. © 2011 Wiley-Liss, Inc.

Tree-Based Unrooted Phylogenetic Networks.

Science.gov (United States)

Francis, A; Huber, K T; Moulton, V

2018-02-01

Phylogenetic networks are a generalization of phylogenetic trees that are used to represent non-tree-like evolutionary histories that arise in organisms such as plants and bacteria, or uncertainty in evolutionary histories. An unrooted phylogenetic network on a non-empty, finite set X of taxa, or network, is a connected, simple graph in which every vertex has degree 1 or 3 and whose leaf set is X. It is called a phylogenetic tree if the underlying graph is a tree. In this paper we consider properties of tree-based networks, that is, networks that can be constructed by adding edges into a phylogenetic tree. We show that although they have some properties in common with their rooted analogues which have recently drawn much attention in the literature, they have some striking differences in terms of both their structural and computational properties. We expect that our results could eventually have applications to, for example, detecting horizontal gene transfer or hybridization which are important factors in the evolution of many organisms.

Phylogenetic framework for coevolutionary studies: a compass for exploring jungles of tangled trees.

Science.gov (United States)

Martínez-Aquino, Andrés

2016-08-01

Phylogenetics is used to detect past evolutionary events, from how species originated to how their ecological interactions with other species arose, which can mirror cophylogenetic patterns. Cophylogenetic reconstructions uncover past ecological relationships between taxa through inferred coevolutionary events on trees, for example, codivergence, duplication, host-switching, and loss. These events can be detected by cophylogenetic analyses based on nodes and the length and branching pattern of the phylogenetic trees of symbiotic associations, for example, host-parasite. In the past 2 decades, algorithms have been developed for cophylogetenic analyses and implemented in different software, for example, statistical congruence index and event-based methods. Based on the combination of these approaches, it is possible to integrate temporal information into cophylogenetical inference, such as estimates of lineage divergence times between 2 taxa, for example, hosts and parasites. Additionally, the advances in phylogenetic biogeography applying methods based on parametric process models and combined Bayesian approaches, can be useful for interpreting coevolutionary histories in a scenario of biogeographical area connectivity through time. This article briefly reviews the basics of parasitology and provides an overview of software packages in cophylogenetic methods. Thus, the objective here is to present a phylogenetic framework for coevolutionary studies, with special emphasis on groups of parasitic organisms. Researchers wishing to undertake phylogeny-based coevolutionary studies can use this review as a "compass" when "walking" through jungles of tangled phylogenetic trees.

Impact of mutations in Toll-like receptor pathway genes on esophageal carcinogenesis.

Directory of Open Access Journals (Sweden)

Daffolyn Rachael Fels Elliott

2017-05-01

Full Text Available Esophageal adenocarcinoma (EAC develops in an inflammatory microenvironment with reduced microbial diversity, but mechanisms for these influences remain poorly characterized. We hypothesized that mutations targeting the Toll-like receptor (TLR pathway could disrupt innate immune signaling and promote a microenvironment that favors tumorigenesis. Through interrogating whole genome sequencing data from 171 EAC patients, we showed that non-synonymous mutations collectively affect the TLR pathway in 25/171 (14.6%, PathScan p = 8.7x10-5 tumors. TLR mutant cases were associated with more proximal tumors and metastatic disease, indicating possible clinical significance of these mutations. Only rare mutations were identified in adjacent Barrett's esophagus samples. We validated our findings in an external EAC dataset with non-synonymous TLR pathway mutations in 33/149 (22.1%, PathScan p = 0.05 tumors, and in other solid tumor types exposed to microbiomes in the COSMIC database (10,318 samples, including uterine endometrioid carcinoma (188/320, 58.8%, cutaneous melanoma (377/988, 38.2%, colorectal adenocarcinoma (402/1519, 26.5%, and stomach adenocarcinoma (151/579, 26.1%. TLR4 was the most frequently mutated gene with eleven mutations in 10/171 (5.8% of EAC tumors. The TLR4 mutants E439G, S570I, F703C and R787H were confirmed to have impaired reactivity to bacterial lipopolysaccharide with marked reductions in signaling by luciferase reporter assays. Overall, our findings show that TLR pathway genes are recurrently mutated in EAC, and TLR4 mutations have decreased responsiveness to bacterial lipopolysaccharide and may play a role in disease pathogenesis in a subset of patients.

Functional and phylogenetic structure of island bird communities.

Science.gov (United States)

Si, Xingfeng; Cadotte, Marc W; Zeng, Di; Baselga, Andrés; Zhao, Yuhao; Li, Jiaqi; Wu, Yiru; Wang, Siyu; Ding, Ping

2017-05-01

Biodiversity change in anthropogenically transformed habitats is often nonrandom, yet the nature and importance of the different mechanisms shaping community structure are unclear. Here, we extend the classic Theory of Island Biogeography (TIB) to account for nonrandom processes by incorporating species traits and phylogenetic relationships into a study of faunal relaxation following habitat loss and fragmentation. Two possible mechanisms can create nonrandom community patterns on fragment islands. First, small and isolated islands might consist of similar or closely related species because they are environmentally homogeneous or select for certain shared traits, such as dispersal ability. Alternatively, communities on small islands might contain more dissimilar or distantly related species than on large islands because limited space and resource availability result in greater competitive exclusion among species with high niche overlap. Breeding birds were surveyed on 36 islands and two mainland sites annually from 2010 to 2014 in the Thousand Island Lake region, China. We assessed community structure of breeding birds on these subtropical land-bridge islands by integrating species' trait and evolutionary distances. We additionally analysed habitat heterogeneity and variance in size ratios to distinguish biotic and abiotic processes of community assembly. Results showed that functional-phylogenetic diversity increased with island area, and decreased with isolation. Bird communities on the mainland were more diverse and generally less clustered than island bird communities and not different than randomly assembled communities. Bird communities on islands tend to be functionally similar and phylogenetically clustered, especially on small and isolated islands. The nonrandom decline in species diversity and change in bird community structure with island area and isolation, along with the relatively homogeneous habitats on small islands, support the environmental

SCREEN FOR DOMINANT BEHAVIORAL MUTATIONS CAUSED BY GENOMIC INSERTION OF P-ELEMENT TRANSPOSONS IN DROSOPHILA: AN EXAMINATION OF THE INTEGRATION OF VIRAL VECTOR SEQUENCES

OpenAIRE

FOX, LYLE E.; GREEN, DAVID; YAN, ZIYING; ENGELHARDT, JOHN F.; WU, CHUN-FANG

2007-01-01

Here we report the development of a high-throughput screen to assess dominant mutation rates caused by P-element transposition within the Drosophila genome that is suitable for assessing the undesirable effects of integrating foreign regulatory sequences (viral cargo) into a host genome. Three different behavioral paradigms were used: sensitivity to mechanical stress, response to heat stress, and ability to fly. The results, from our screen of 35,000 flies, indicate that mutations caused by t...

SEM analysis of ionizing radiation effects in linear integrated circuits. [Scanning Electron Microscope

Science.gov (United States)

Stanley, A. G.; Gauthier, M. K.

1977-01-01

A successful diagnostic technique was developed using a scanning electron microscope (SEM) as a precision tool to determine ionization effects in integrated circuits. Previous SEM methods radiated the entire semiconductor chip or major areas. The large area exposure methods do not reveal the exact components which are sensitive to radiation. To locate these sensitive components a new method was developed, which consisted in successively irradiating selected components on the device chip with equal doses of electrons /10 to the 6th rad (Si)/, while the whole device was subjected to representative bias conditions. A suitable device parameter was measured in situ after each successive irradiation with the beam off.

Nodal distances for rooted phylogenetic trees.

Science.gov (United States)

Cardona, Gabriel; Llabrés, Mercè; Rosselló, Francesc; Valiente, Gabriel

2010-08-01

Dissimilarity measures for (possibly weighted) phylogenetic trees based on the comparison of their vectors of path lengths between pairs of taxa, have been present in the systematics literature since the early seventies. For rooted phylogenetic trees, however, these vectors can only separate non-weighted binary trees, and therefore these dissimilarity measures are metrics only on this class of rooted phylogenetic trees. In this paper we overcome this problem, by splitting in a suitable way each path length between two taxa into two lengths. We prove that the resulting splitted path lengths matrices single out arbitrary rooted phylogenetic trees with nested taxa and arcs weighted in the set of positive real numbers. This allows the definition of metrics on this general class of rooted phylogenetic trees by comparing these matrices through metrics in spaces M(n)(R) of real-valued n x n matrices. We conclude this paper by establishing some basic facts about the metrics for non-weighted phylogenetic trees defined in this way using L(p) metrics on M(n)(R), with p [epsilon] R(>0).

Direct Transcriptional Consequences of Somatic Mutation in Breast Cancer

Directory of Open Access Journals (Sweden)

Adam Shlien

2016-08-01

Full Text Available Disordered transcriptomes of cancer encompass direct effects of somatic mutation on transcription, coordinated secondary pathway alterations, and increased transcriptional noise. To catalog the rules governing how somatic mutation exerts direct transcriptional effects, we developed an exhaustive pipeline for analyzing RNA sequencing data, which we integrated with whole genomes from 23 breast cancers. Using X-inactivation analyses, we found that cancer cells are more transcriptionally active than intermixed stromal cells. This is especially true in estrogen receptor (ER-negative tumors. Overall, 59% of substitutions were expressed. Nonsense mutations showed lower expression levels than expected, with patterns characteristic of nonsense-mediated decay. 14% of 4,234 rearrangements caused transcriptional abnormalities, including exon skips, exon reusage, fusions, and premature polyadenylation. We found productive, stable transcription from sense-to-antisense gene fusions and gene-to-intergenic rearrangements, suggesting that these mutation classes drive more transcriptional disruption than previously suspected. Systematic integration of transcriptome with genome data reveals the rules by which transcriptional machinery interprets somatic mutation.

Ant-Based Phylogenetic Reconstruction (ABPR: A new distance algorithm for phylogenetic estimation based on ant colony optimization

Directory of Open Access Journals (Sweden)

Karla Vittori

2008-12-01

Full Text Available We propose a new distance algorithm for phylogenetic estimation based on Ant Colony Optimization (ACO, named Ant-Based Phylogenetic Reconstruction (ABPR. ABPR joins two taxa iteratively based on evolutionary distance among sequences, while also accounting for the quality of the phylogenetic tree built according to the total length of the tree. Similar to optimization algorithms for phylogenetic estimation, the algorithm allows exploration of a larger set of nearly optimal solutions. We applied the algorithm to four empirical data sets of mitochondrial DNA ranging from 12 to 186 sequences, and from 898 to 16,608 base pairs, and covering taxonomic levels from populations to orders. We show that ABPR performs better than the commonly used Neighbor-Joining algorithm, except when sequences are too closely related (e.g., population-level sequences. The phylogenetic relationships recovered at and above species level by ABPR agree with conventional views. However, like other algorithms of phylogenetic estimation, the proposed algorithm failed to recover expected relationships when distances are too similar or when rates of evolution are very variable, leading to the problem of long-branch attraction. ABPR, as well as other ACO-based algorithms, is emerging as a fast and accurate alternative method of phylogenetic estimation for large data sets.

Systematic Analysis of Splice-Site-Creating Mutations in Cancer

Directory of Open Access Journals (Sweden)

Reyka G. Jayasinghe

2018-04-01

Full Text Available Summary: For the past decade, cancer genomic studies have focused on mutations leading to splice-site disruption, overlooking those having splice-creating potential. Here, we applied a bioinformatic tool, MiSplice, for the large-scale discovery of splice-site-creating mutations (SCMs across 8,656 TCGA tumors. We report 1,964 originally mis-annotated mutations having clear evidence of creating alternative splice junctions. TP53 and GATA3 have 26 and 18 SCMs, respectively, and ATRX has 5 from lower-grade gliomas. Mutations in 11 genes, including PARP1, BRCA1, and BAP1, were experimentally validated for splice-site-creating function. Notably, we found that neoantigens induced by SCMs are likely several folds more immunogenic compared to missense mutations, exemplified by the recurrent GATA3 SCM. Further, high expression of PD-1 and PD-L1 was observed in tumors with SCMs, suggesting candidates for immune blockade therapy. Our work highlights the importance of integrating DNA and RNA data for understanding the functional and the clinical implications of mutations in human diseases. : Jayasinghe et al. identify nearly 2,000 splice-site-creating mutations (SCMs from over 8,000 tumor samples across 33 cancer types. They provide a more accurate interpretation of previously mis-annotated mutations, highlighting the importance of integrating data types to understand the functional and the clinical implications of splicing mutations in human disease. Keywords: splicing, RNA, mutations of clinical relevance

Integrating visible light 3D scanning into the everyday world

Science.gov (United States)

Straub, Jeremy

2015-05-01

Visible light 3D scanning offers the potential to non-invasively and nearly non-perceptibly incorporate 3D imaging into the everyday world. This paper considers the various possible uses of visible light 3D scanning technology. It discusses multiple possible usage scenarios including in hospitals, security perimeter settings and retail environments. The paper presents a framework for assessing the efficacy of visible light 3D scanning for a given application (and compares this to other scanning approaches such as those using blue light or lasers). It also discusses ethical and legal considerations relevant to real-world use and concludes by presenting a decision making framework.

On Tree-Based Phylogenetic Networks.

Science.gov (United States)

Zhang, Louxin

2016-07-01

A large class of phylogenetic networks can be obtained from trees by the addition of horizontal edges between the tree edges. These networks are called tree-based networks. We present a simple necessary and sufficient condition for tree-based networks and prove that a universal tree-based network exists for any number of taxa that contains as its base every phylogenetic tree on the same set of taxa. This answers two problems posted by Francis and Steel recently. A byproduct is a computer program for generating random binary phylogenetic networks under the uniform distribution model.

The Mutational Robustness of Influenza A Virus.

Directory of Open Access Journals (Sweden)

Elisa Visher

2016-08-01

Full Text Available A virus' mutational robustness is described in terms of the strength and distribution of the mutational fitness effects, or MFE. The distribution of MFE is central to many questions in evolutionary theory and is a key parameter in models of molecular evolution. Here we define the mutational fitness effects in influenza A virus by generating 128 viruses, each with a single nucleotide mutation. In contrast to mutational scanning approaches, this strategy allowed us to unambiguously assign fitness values to individual mutations. The presence of each desired mutation and the absence of additional mutations were verified by next generation sequencing of each stock. A mutation was considered lethal only after we failed to rescue virus in three independent transfections. We measured the fitness of each viable mutant relative to the wild type by quantitative RT-PCR following direct competition on A549 cells. We found that 31.6% of the mutations in the genome-wide dataset were lethal and that the lethal fraction did not differ appreciably between the HA- and NA-encoding segments and the rest of the genome. Of the viable mutants, the fitness mean and standard deviation were 0.80 and 0.22 in the genome-wide dataset and best modeled as a beta distribution. The fitness impact of mutation was marginally lower in the segments coding for HA and NA (0.88 ± 0.16 than in the other 6 segments (0.78 ± 0.24, and their respective beta distributions had slightly different shape parameters. The results for influenza A virus are remarkably similar to our own analysis of CirSeq-derived fitness values from poliovirus and previously published data from other small, single stranded DNA and RNA viruses. These data suggest that genome size, and not nucleic acid type or mode of replication, is the main determinant of viral mutational fitness effects.

Phylemon 2.0: a suite of web-tools for molecular evolution, phylogenetics, phylogenomics and hypotheses testing.

Science.gov (United States)

Sánchez, Rubén; Serra, François; Tárraga, Joaquín; Medina, Ignacio; Carbonell, José; Pulido, Luis; de María, Alejandro; Capella-Gutíerrez, Salvador; Huerta-Cepas, Jaime; Gabaldón, Toni; Dopazo, Joaquín; Dopazo, Hernán

2011-07-01

Phylemon 2.0 is a new release of the suite of web tools for molecular evolution, phylogenetics, phylogenomics and hypotheses testing. It has been designed as a response to the increasing demand of molecular sequence analyses for experts and non-expert users. Phylemon 2.0 has several unique features that differentiates it from other similar web resources: (i) it offers an integrated environment that enables evolutionary analyses, format conversion, file storage and edition of results; (ii) it suggests further analyses, thereby guiding the users through the web server; and (iii) it allows users to design and save phylogenetic pipelines to be used over multiple genes (phylogenomics). Altogether, Phylemon 2.0 integrates a suite of 30 tools covering sequence alignment reconstruction and trimming; tree reconstruction, visualization and manipulation; and evolutionary hypotheses testing.

Phylemon 2.0: a suite of web-tools for molecular evolution, phylogenetics, phylogenomics and hypotheses testing

Science.gov (United States)

Sánchez, Rubén; Serra, François; Tárraga, Joaquín; Medina, Ignacio; Carbonell, José; Pulido, Luis; de María, Alejandro; Capella-Gutíerrez, Salvador; Huerta-Cepas, Jaime; Gabaldón, Toni; Dopazo, Joaquín; Dopazo, Hernán

2011-01-01

Phylemon 2.0 is a new release of the suite of web tools for molecular evolution, phylogenetics, phylogenomics and hypotheses testing. It has been designed as a response to the increasing demand of molecular sequence analyses for experts and non-expert users. Phylemon 2.0 has several unique features that differentiates it from other similar web resources: (i) it offers an integrated environment that enables evolutionary analyses, format conversion, file storage and edition of results; (ii) it suggests further analyses, thereby guiding the users through the web server; and (iii) it allows users to design and save phylogenetic pipelines to be used over multiple genes (phylogenomics). Altogether, Phylemon 2.0 integrates a suite of 30 tools covering sequence alignment reconstruction and trimming; tree reconstruction, visualization and manipulation; and evolutionary hypotheses testing. PMID:21646336

Functional & phylogenetic diversity of copepod communities

Science.gov (United States)

Benedetti, F.; Ayata, S. D.; Blanco-Bercial, L.; Cornils, A.; Guilhaumon, F.

2016-02-01

The diversity of natural communities is classically estimated through species identification (taxonomic diversity) but can also be estimated from the ecological functions performed by the species (functional diversity), or from the phylogenetic relationships among them (phylogenetic diversity). Estimating functional diversity requires the definition of specific functional traits, i.e., phenotypic characteristics that impact fitness and are relevant to ecosystem functioning. Estimating phylogenetic diversity requires the description of phylogenetic relationships, for instance by using molecular tools. In the present study, we focused on the functional and phylogenetic diversity of copepod surface communities in the Mediterranean Sea. First, we implemented a specific trait database for the most commonly-sampled and abundant copepod species of the Mediterranean Sea. Our database includes 191 species, described by seven traits encompassing diverse ecological functions: minimal and maximal body length, trophic group, feeding type, spawning strategy, diel vertical migration and vertical habitat. Clustering analysis in the functional trait space revealed that Mediterranean copepods can be gathered into groups that have different ecological roles. Second, we reconstructed a phylogenetic tree using the available sequences of 18S rRNA. Our tree included 154 of the analyzed Mediterranean copepod species. We used these two datasets to describe the functional and phylogenetic diversity of copepod surface communities in the Mediterranean Sea. The replacement component (turn-over) and the species richness difference component (nestedness) of the beta diversity indices were identified. Finally, by comparing various and complementary aspects of plankton diversity (taxonomic, functional, and phylogenetic diversity) we were able to gain a better understanding of the relationships among the zooplankton community, biodiversity, ecosystem function, and environmental forcing.

Phylogenetic diversity and relationships among species of genus ...

African Journals Online (AJOL)

Fifty six Nicotiana species were used to construct phylogenetic trees and to asses the genetic relationships between them. Genetic distances estimated from RAPD analysis was used to construct phylogenetic trees using Phylogenetic Inference Package (PHYLIP). Since phylogenetic relationships estimated for closely ...

Multiple alignment analysis on phylogenetic tree of the spread of SARS epidemic using distance method

Science.gov (United States)

Amiroch, S.; Pradana, M. S.; Irawan, M. I.; Mukhlash, I.

2017-09-01

Multiple Alignment (MA) is a particularly important tool for studying the viral genome and determine the evolutionary process of the specific virus. Application of MA in the case of the spread of the Severe acute respiratory syndrome (SARS) epidemic is an interesting thing because this virus epidemic a few years ago spread so quickly that medical attention in many countries. Although there has been a lot of software to process multiple sequences, but the use of pairwise alignment to process MA is very important to consider. In previous research, the alignment between the sequences to process MA algorithm, Super Pairwise Alignment, but in this study used a dynamic programming algorithm Needleman wunchs simulated in Matlab. From the analysis of MA obtained and stable region and unstable which indicates the position where the mutation occurs, the system network topology that produced the phylogenetic tree of the SARS epidemic distance method, and system area networks mutation.

Nonbinary Tree-Based Phylogenetic Networks

NARCIS (Netherlands)

Jetten, L.; van Iersel, L.J.J.

2018-01-01

Rooted phylogenetic networks are used to describe evolutionary histories that contain non-treelike evolutionary events such as hybridization and horizontal gene transfer. In some cases, such histories can be described by a phylogenetic base-tree with additional linking arcs, which can for example

The Maia Spectroscopy Detector System: Engineering for Integrated Pulse Capture, Low-Latency Scanning and Real-Time Processing

International Nuclear Information System (INIS)

Kirkham, R.; Siddons, D.; Dunn, P.A.; Kuczewski, A.J.; Dodanwela, R.; Moorhead, G.F.; Ryan, C.G.; De Geronimo, G.; Beuttenmuller, R.; Pinelli, D.; Pfeffer, M.; Davey, P.; Jensen, M.; de Jonge, M.D.; Howard, D.L.; Kusel, M.; McKinlay, J.

2010-01-01

The Maia detector system is engineered for energy dispersive x-ray fluorescence spectroscopy and elemental imaging at photon rates exceeding 10 7 /s, integrated scanning of samples for pixel transit times as small as 50 (micro)s and high definition images of 10 8 pixels and real-time processing of detected events for spectral deconvolution and online display of pure elemental images. The system developed by CSIRO and BNL combines a planar silicon 384 detector array, application-specific integrated circuits for pulse shaping and peak detection and sampling and optical data transmission to an FPGA-based pipelined, parallel processor. This paper describes the system and the underpinning engineering solutions.

Including RNA secondary structures improves accuracy and robustness in reconstruction of phylogenetic trees.

Science.gov (United States)

Keller, Alexander; Förster, Frank; Müller, Tobias; Dandekar, Thomas; Schultz, Jörg; Wolf, Matthias

2010-01-15

In several studies, secondary structures of ribosomal genes have been used to improve the quality of phylogenetic reconstructions. An extensive evaluation of the benefits of secondary structure, however, is lacking. This is the first study to counter this deficiency. We inspected the accuracy and robustness of phylogenetics with individual secondary structures by simulation experiments for artificial tree topologies with up to 18 taxa and for divergency levels in the range of typical phylogenetic studies. We chose the internal transcribed spacer 2 of the ribosomal cistron as an exemplary marker region. Simulation integrated the coevolution process of sequences with secondary structures. Additionally, the phylogenetic power of marker size duplication was investigated and compared with sequence and sequence-structure reconstruction methods. The results clearly show that accuracy and robustness of Neighbor Joining trees are largely improved by structural information in contrast to sequence only data, whereas a doubled marker size only accounts for robustness. Individual secondary structures of ribosomal RNA sequences provide a valuable gain of information content that is useful for phylogenetics. Thus, the usage of ITS2 sequence together with secondary structure for taxonomic inferences is recommended. Other reconstruction methods as maximum likelihood, bayesian inference or maximum parsimony may equally profit from secondary structure inclusion. This article was reviewed by Shamil Sunyaev, Andrea Tanzer (nominated by Frank Eisenhaber) and Eugene V. Koonin. Reviewed by Shamil Sunyaev, Andrea Tanzer (nominated by Frank Eisenhaber) and Eugene V. Koonin. For the full reviews, please go to the Reviewers' comments section.

JAK2 and MPL gene mutations in V617F-negative myeloproliferative neoplasms.

NARCIS (Netherlands)

Siemiatkowska, A.M.; Bieniaszewska, M.; Hellmann, A.; Limon, J.

2010-01-01

We report three novel mutations in JAK2 exons 12, 19 and 25 in V617F-negative patients with polycythemia vera, essential thrombocythemia and idiopathic myelofibrosis. Scanning of JAK2 exons 12-25 and MPL exon 10 revealed the presence of JAK2 alterations in six and MPL W515L/K mutations in five of 34

Ultrafast Approximation for Phylogenetic Bootstrap

NARCIS (Netherlands)

Bui Quang Minh, [No Value; Nguyen, Thi; von Haeseler, Arndt

Nonparametric bootstrap has been a widely used tool in phylogenetic analysis to assess the clade support of phylogenetic trees. However, with the rapidly growing amount of data, this task remains a computational bottleneck. Recently, approximation methods such as the RAxML rapid bootstrap (RBS) and

Different relationships between temporal phylogenetic turnover and phylogenetic similarity and in two forests were detected by a new null model.

Science.gov (United States)

Huang, Jian-Xiong; Zhang, Jian; Shen, Yong; Lian, Ju-yu; Cao, Hong-lin; Ye, Wan-hui; Wu, Lin-fang; Bin, Yue

2014-01-01

Ecologists have been monitoring community dynamics with the purpose of understanding the rates and causes of community change. However, there is a lack of monitoring of community dynamics from the perspective of phylogeny. We attempted to understand temporal phylogenetic turnover in a 50 ha tropical forest (Barro Colorado Island, BCI) and a 20 ha subtropical forest (Dinghushan in southern China, DHS). To obtain temporal phylogenetic turnover under random conditions, two null models were used. The first shuffled names of species that are widely used in community phylogenetic analyses. The second simulated demographic processes with careful consideration on the variation in dispersal ability among species and the variations in mortality both among species and among size classes. With the two models, we tested the relationships between temporal phylogenetic turnover and phylogenetic similarity at different spatial scales in the two forests. Results were more consistent with previous findings using the second null model suggesting that the second null model is more appropriate for our purposes. With the second null model, a significantly positive relationship was detected between phylogenetic turnover and phylogenetic similarity in BCI at a 10 m×10 m scale, potentially indicating phylogenetic density dependence. This relationship in DHS was significantly negative at three of five spatial scales. This could indicate abiotic filtering processes for community assembly. Using variation partitioning, we found phylogenetic similarity contributed to variation in temporal phylogenetic turnover in the DHS plot but not in BCI plot. The mechanisms for community assembly in BCI and DHS vary from phylogenetic perspective. Only the second null model detected this difference indicating the importance of choosing a proper null model.

Undergraduate Students’ Difficulties in Reading and Constructing Phylogenetic Tree

Science.gov (United States)

Sa'adah, S.; Tapilouw, F. S.; Hidayat, T.

2017-02-01

Representation is a very important communication tool to communicate scientific concepts. Biologists produce phylogenetic representation to express their understanding of evolutionary relationships. The phylogenetic tree is visual representation depict a hypothesis about the evolutionary relationship and widely used in the biological sciences. Phylogenetic tree currently growing for many disciplines in biology. Consequently, learning about phylogenetic tree become an important part of biological education and an interesting area for biology education research. However, research showed many students often struggle with interpreting the information that phylogenetic trees depict. The purpose of this study was to investigate undergraduate students’ difficulties in reading and constructing a phylogenetic tree. The method of this study is a descriptive method. In this study, we used questionnaires, interviews, multiple choice and open-ended questions, reflective journals and observations. The findings showed students experiencing difficulties, especially in constructing a phylogenetic tree. The students’ responds indicated that main reasons for difficulties in constructing a phylogenetic tree are difficult to placing taxa in a phylogenetic tree based on the data provided so that the phylogenetic tree constructed does not describe the actual evolutionary relationship (incorrect relatedness). Students also have difficulties in determining the sister group, character synapomorphy, autapomorphy from data provided (character table) and comparing among phylogenetic tree. According to them building the phylogenetic tree is more difficult than reading the phylogenetic tree. Finding this studies provide information to undergraduate instructor and students to overcome learning difficulties of reading and constructing phylogenetic tree.

Deep Sequence Analysis of Non-Small Cell Lung Cancer: Integrated Analysis of Gene Expression, Alternative Splicing, and Single Nucleotide Variations in Lung Adenocarcinomas with and without Oncogenic KRAS Mutations

International Nuclear Information System (INIS)

Kalari, Krishna R.; Rossell, David; Necela, Brian M.; Asmann, Yan W.; Nair, Asha

2012-01-01

KRAS mutations are highly prevalent in non-small cell lung cancer (NSCLC), and tumors harboring these mutations tend to be aggressive and resistant to chemotherapy. We used next-generation sequencing technology to identify pathways that are specifically altered in lung tumors harboring a KRAS mutation. Paired-end RNA-sequencing of 15 primary lung adenocarcinoma tumors (8 harboring mutant KRAS and 7 with wild-type KRAS) were performed. Sequences were mapped to the human genome, and genomic features, including differentially expressed genes, alternate splicing isoforms and single nucleotide variants, were determined for tumors with and without KRAS mutation using a variety of computational methods. Network analysis was carried out on genes showing differential expression (374 genes), alternate splicing (259 genes), and SNV-related changes (65 genes) in NSCLC tumors harboring a KRAS mutation. Genes exhibiting two or more connections from the lung adenocarcinoma network were used to carry out integrated pathway analysis. The most significant signaling pathways identified through this analysis were the NFκB, ERK1/2, and AKT pathways. A 27 gene mutant KRAS-specific sub network was extracted based on gene–gene connections from the integrated network, and interrogated for druggable targets. Our results confirm previous evidence that mutant KRAS tumors exhibit activated NFκB, ERK1/2, and AKT pathways and may be preferentially sensitive to target therapeutics toward these pathways. In addition, our analysis indicates novel, previously unappreciated links between mutant KRAS and the TNFR and PPARγ signaling pathways, suggesting that targeted PPARγ antagonists and TNFR inhibitors may be useful therapeutic strategies for treatment of mutant KRAS lung tumors. Our study is the first to integrate genomic features from RNA-Seq data from NSCLC and to define a first draft genomic landscape model that is unique to tumors with oncogenic KRAS mutations.

Phylogenetic structure in tropical hummingbird communities

DEFF Research Database (Denmark)

Graham, Catherine H; Parra, Juan L; Rahbek, Carsten

2009-01-01

How biotic interactions, current and historical environment, and biogeographic barriers determine community structure is a fundamental question in ecology and evolution, especially in diverse tropical regions. To evaluate patterns of local and regional diversity, we quantified the phylogenetic...... composition of 189 hummingbird communities in Ecuador. We assessed how species and phylogenetic composition changed along environmental gradients and across biogeographic barriers. We show that humid, low-elevation communities are phylogenetically overdispersed (coexistence of distant relatives), a pattern...... that is consistent with the idea that competition influences the local composition of hummingbirds. At higher elevations communities are phylogenetically clustered (coexistence of close relatives), consistent with the expectation of environmental filtering, which may result from the challenge of sustaining...

Constructing phylogenetic trees using interacting pathways.

Science.gov (United States)

Wan, Peng; Che, Dongsheng

2013-01-01

Phylogenetic trees are used to represent evolutionary relationships among biological species or organisms. The construction of phylogenetic trees is based on the similarities or differences of their physical or genetic features. Traditional approaches of constructing phylogenetic trees mainly focus on physical features. The recent advancement of high-throughput technologies has led to accumulation of huge amounts of biological data, which in turn changed the way of biological studies in various aspects. In this paper, we report our approach of building phylogenetic trees using the information of interacting pathways. We have applied hierarchical clustering on two domains of organisms-eukaryotes and prokaryotes. Our preliminary results have shown the effectiveness of using the interacting pathways in revealing evolutionary relationships.

The effect of charge-introduction mutations on E. coli thioredoxin stability.

Science.gov (United States)

Perez-Jimenez, Raul; Godoy-Ruiz, Raquel; Ibarra-Molero, Beatriz; Sanchez-Ruiz, Jose M

2005-04-01

Technological applications of proteins are often hampered by their low-stability and, consequently, the development of procedures for protein stabilization is of considerable biotechnological interest. Here, we use simple electrostatics to determine positions in E. coli thioredoxin at which mutations that introduce new charged residues are expected to lead to stability enhancement. We also obtain the corresponding mutants and characterize their stability using differential scanning calorimetry. The results are interpreted in terms of the accessibility in the native structure of the mutated residues and the potential effect of the mutations on the residual structure of the denatured state.

In vivo integrated photoacoustic ophthalmoscopy, optical coherence tomography, and scanning laser ophthalmoscopy for retinal imaging

Science.gov (United States)

Song, Wei; Zhang, Rui; Zhang, Hao F.; Wei, Qing; Cao, Wenwu

2012-12-01

The physiological and pathological properties of retina are closely associated with various optical contrasts. Hence, integrating different ophthalmic imaging technologies is more beneficial in both fundamental investigation and clinical diagnosis of several blinding diseases. Recently, photoacoustic ophthalmoscopy (PAOM) was developed for in vivo retinal imaging in small animals, which demonstrated the capability of imaging retinal vascular networks and retinal pigment epithelium (RPE) at high sensitivity. We combined PAOM with traditional imaging modalities, such as fluorescein angiography (FA), spectral-domain optical coherence tomography (SD-OCT), and auto-fluorescence scanning laser ophthalmoscopy (AF-SLO), for imaging rats and mice. The multimodal imaging system provided more comprehensive evaluation of the retina based on the complementary imaging contrast mechanisms. The high-quality retinal images show that the integrated ophthalmic imaging system has great potential in the investigation of blinding disorders.

Inferring Phylogenetic Networks Using PhyloNet.

Science.gov (United States)

Wen, Dingqiao; Yu, Yun; Zhu, Jiafan; Nakhleh, Luay

2018-07-01

PhyloNet was released in 2008 as a software package for representing and analyzing phylogenetic networks. At the time of its release, the main functionalities in PhyloNet consisted of measures for comparing network topologies and a single heuristic for reconciling gene trees with a species tree. Since then, PhyloNet has grown significantly. The software package now includes a wide array of methods for inferring phylogenetic networks from data sets of unlinked loci while accounting for both reticulation (e.g., hybridization) and incomplete lineage sorting. In particular, PhyloNet now allows for maximum parsimony, maximum likelihood, and Bayesian inference of phylogenetic networks from gene tree estimates. Furthermore, Bayesian inference directly from sequence data (sequence alignments or biallelic markers) is implemented. Maximum parsimony is based on an extension of the "minimizing deep coalescences" criterion to phylogenetic networks, whereas maximum likelihood and Bayesian inference are based on the multispecies network coalescent. All methods allow for multiple individuals per species. As computing the likelihood of a phylogenetic network is computationally hard, PhyloNet allows for evaluation and inference of networks using a pseudolikelihood measure. PhyloNet summarizes the results of the various analyzes and generates phylogenetic networks in the extended Newick format that is readily viewable by existing visualization software.

galaxieEST: addressing EST identity through automated phylogenetic analysis.

Science.gov (United States)

Nilsson, R Henrik; Rajashekar, Balaji; Larsson, Karl-Henrik; Ursing, Björn M

2004-07-05

Research involving expressed sequence tags (ESTs) is intricately coupled to the existence of large, well-annotated sequence repositories. Comparatively complete and satisfactory annotated public sequence libraries are, however, available only for a limited range of organisms, rendering the absence of sequences and gene structure information a tangible problem for those working with taxa lacking an EST or genome sequencing project. Paralogous genes belonging to the same gene family but distinguished by derived characteristics are particularly prone to misidentification and erroneous annotation; high but incomplete levels of sequence similarity are typically difficult to interpret and have formed the basis of many unsubstantiated assumptions of orthology. In these cases, a phylogenetic study of the query sequence together with the most similar sequences in the database may be of great value to the identification process. In order to facilitate this laborious procedure, a project to employ automated phylogenetic analysis in the identification of ESTs was initiated. galaxieEST is an open source Perl-CGI script package designed to complement traditional similarity-based identification of EST sequences through employment of automated phylogenetic analysis. It uses a series of BLAST runs as a sieve to retrieve nucleotide and protein sequences for inclusion in neighbour joining and parsimony analyses; the output includes the BLAST output, the results of the phylogenetic analyses, and the corresponding multiple alignments. galaxieEST is available as an on-line web service for identification of fungal ESTs and for download / local installation for use with any organism group at http://galaxie.cgb.ki.se/galaxieEST.html. By addressing sequence relatedness in addition to similarity, galaxieEST provides an integrative view on EST origin and identity, which may prove particularly useful in cases where similarity searches return one or more pertinent, but not full, matches and

The relationship of different somatic mutations induced by neutrons and X rays to loss of reproductive integrity in Tradescantia stamen hairs

International Nuclear Information System (INIS)

Underbrink, A.G.; Huczkowski, J.; Woch, B.; Gedlek, E.; Cebulska-Wasilewska, A.; Litwiniszyn, M.; Kasper, E.

1978-01-01

It was found that the survival curves derived from X-irradiations and neutrons of two energies are characteristic for those usually found in many other systems. It was also found that the loss of reproductive integrity and two visible cell-type aberrations or mutations follow a 1:1 ratio until higher doses are reached after neutron irradiation. This is also true for X rays, except that lethality was not observed at relatively low doses. The mutant event spectrum was found to change after a certain level of lethality was reached. It was also found that the spectra of mutations in relation to survival may be changed not only by dose but also by radiation quality. (author)

Phylogenetic classification of bony fishes.

Science.gov (United States)

Betancur-R, Ricardo; Wiley, Edward O; Arratia, Gloria; Acero, Arturo; Bailly, Nicolas; Miya, Masaki; Lecointre, Guillaume; Ortí, Guillermo

2017-07-06

Fish classifications, as those of most other taxonomic groups, are being transformed drastically as new molecular phylogenies provide support for natural groups that were unanticipated by previous studies. A brief review of the main criteria used by ichthyologists to define their classifications during the last 50 years, however, reveals slow progress towards using an explicit phylogenetic framework. Instead, the trend has been to rely, in varying degrees, on deep-rooted anatomical concepts and authority, often mixing taxa with explicit phylogenetic support with arbitrary groupings. Two leading sources in ichthyology frequently used for fish classifications (JS Nelson's volumes of Fishes of the World and W. Eschmeyer's Catalog of Fishes) fail to adopt a global phylogenetic framework despite much recent progress made towards the resolution of the fish Tree of Life. The first explicit phylogenetic classification of bony fishes was published in 2013, based on a comprehensive molecular phylogeny ( www.deepfin.org ). We here update the first version of that classification by incorporating the most recent phylogenetic results. The updated classification presented here is based on phylogenies inferred using molecular and genomic data for nearly 2000 fishes. A total of 72 orders (and 79 suborders) are recognized in this version, compared with 66 orders in version 1. The phylogeny resolves placement of 410 families, or ~80% of the total of 514 families of bony fishes currently recognized. The ordinal status of 30 percomorph families included in this study, however, remains uncertain (incertae sedis in the series Carangaria, Ovalentaria, or Eupercaria). Comments to support taxonomic decisions and comparisons with conflicting taxonomic groups proposed by others are presented. We also highlight cases were morphological support exist for the groups being classified. This version of the phylogenetic classification of bony fishes is substantially improved, providing resolution

The space of ultrametric phylogenetic trees.

Science.gov (United States)

Gavryushkin, Alex; Drummond, Alexei J

2016-08-21

The reliability of a phylogenetic inference method from genomic sequence data is ensured by its statistical consistency. Bayesian inference methods produce a sample of phylogenetic trees from the posterior distribution given sequence data. Hence the question of statistical consistency of such methods is equivalent to the consistency of the summary of the sample. More generally, statistical consistency is ensured by the tree space used to analyse the sample. In this paper, we consider two standard parameterisations of phylogenetic time-trees used in evolutionary models: inter-coalescent interval lengths and absolute times of divergence events. For each of these parameterisations we introduce a natural metric space on ultrametric phylogenetic trees. We compare the introduced spaces with existing models of tree space and formulate several formal requirements that a metric space on phylogenetic trees must possess in order to be a satisfactory space for statistical analysis, and justify them. We show that only a few known constructions of the space of phylogenetic trees satisfy these requirements. However, our results suggest that these basic requirements are not enough to distinguish between the two metric spaces we introduce and that the choice between metric spaces requires additional properties to be considered. Particularly, that the summary tree minimising the square distance to the trees from the sample might be different for different parameterisations. This suggests that further fundamental insight is needed into the problem of statistical consistency of phylogenetic inference methods. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Data set for phylogenetic tree and RAMPAGE Ramachandran plot analysis of SODs in Gossypium raimondii and G. arboreum.

Science.gov (United States)

Wang, Wei; Xia, Minxuan; Chen, Jie; Deng, Fenni; Yuan, Rui; Zhang, Xiaopei; Shen, Fafu

2016-12-01

The data presented in this paper is supporting the research article "Genome-Wide Analysis of Superoxide Dismutase Gene Family in Gossypium raimondii and G. arboreum" [1]. In this data article, we present phylogenetic tree showing dichotomy with two different clusters of SODs inferred by the Bayesian method of MrBayes (version 3.2.4), "Bayesian phylogenetic inference under mixed models" [2], Ramachandran plots of G. raimondii and G. arboreum SODs, the protein sequence used to generate 3D sructure of proteins and the template accession via SWISS-MODEL server, "SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information." [3] and motif sequences of SODs identified by InterProScan (version 4.8) with the Pfam database, "Pfam: the protein families database" [4].

A Novel Integrated Algorithm for Wind Vector Retrieval from Conically Scanning Scatterometers

Directory of Open Access Journals (Sweden)

Xuetong Xie

2013-11-01

Full Text Available Due to the lower efficiency and the larger wind direction error of traditional algorithms, a novel integrated wind retrieval algorithm is proposed for conically scanning scatterometers. The proposed algorithm has the dual advantages of less computational cost and higher wind direction retrieval accuracy by integrating the wind speed standard deviation (WSSD algorithm and the wind direction interval retrieval (DIR algorithm. It adopts wind speed standard deviation as a criterion for searching possible wind vector solutions and retrieving a potential wind direction interval based on the change rate of the wind speed standard deviation. Moreover, a modified three-step ambiguity removal method is designed to let more wind directions be selected in the process of nudging and filtering. The performance of the new algorithm is illustrated by retrieval experiments using 300 orbits of SeaWinds/QuikSCAT L2A data (backscatter coefficients at 25 km resolution and co-located buoy data. Experimental results indicate that the new algorithm can evidently enhance the wind direction retrieval accuracy, especially in the nadir region. In comparison with the SeaWinds L2B Version 2 25 km selected wind product (retrieved wind fields, an improvement of 5.1° in wind direction retrieval can be made by the new algorithm for that region.

phangorn: phylogenetic analysis in R.

Science.gov (United States)

Schliep, Klaus Peter

2011-02-15

phangorn is a package for phylogenetic reconstruction and analysis in the R language. Previously it was only possible to estimate phylogenetic trees with distance methods in R. phangorn, now offers the possibility of reconstructing phylogenies with distance based methods, maximum parsimony or maximum likelihood (ML) and performing Hadamard conjugation. Extending the general ML framework, this package provides the possibility of estimating mixture and partition models. Furthermore, phangorn offers several functions for comparing trees, phylogenetic models or splits, simulating character data and performing congruence analyses. phangorn can be obtained through the CRAN homepage http://cran.r-project.org/web/packages/phangorn/index.html. phangorn is licensed under GPL 2.

Presymptomatic generalized brain atrophy in frontotemporal dementia caused by CHMP2B mutation

DEFF Research Database (Denmark)

Rohrer, Jonathan D; Ahsan, R Laila; Isaacs, Adrian M

2009-01-01

mutation carriers with a control group of 7 mutation-negative family members. Volumetric MRI brain scans were performed on all subjects at two time points, and rates of volume change were compared between the two groups. RESULTS: We demonstrate that generalized atrophy occurs presymptomatically in CHMP2B...... gene mutation carriers. CONCLUSIONS: This finding suggests that mutations in CHMP2B have widespread effects throughout the brain, leading to a neuro-anatomical signature distinct from other diseases in the frontotemporal lobar degeneration spectrum........ There are no detailed studies of brain imaging in CHMP2B mutation-associated FTD. This study aimed to investigate whether there were early or presymptomatic changes in this group of patients. METHODS: Subjects comprised 16 members of a Danish family with CHMP2B mutation-associated FTD. Nine subjects were presymptomatic...

Undergraduate Students’ Initial Ability in Understanding Phylogenetic Tree

Science.gov (United States)

Sa'adah, S.; Hidayat, T.; Sudargo, Fransisca

2017-04-01

The Phylogenetic tree is a visual representation depicts a hypothesis about the evolutionary relationship among taxa. Evolutionary experts use this representation to evaluate the evidence for evolution. The phylogenetic tree is currently growing for many disciplines in biology. Consequently, learning about the phylogenetic tree has become an important part of biological education and an interesting area of biology education research. Skill to understanding and reasoning of the phylogenetic tree, (called tree thinking) is an important skill for biology students. However, research showed many students have difficulty in interpreting, constructing, and comparing among the phylogenetic tree, as well as experiencing a misconception in the understanding of the phylogenetic tree. Students are often not taught how to reason about evolutionary relationship depicted in the diagram. Students are also not provided with information about the underlying theory and process of phylogenetic. This study aims to investigate the initial ability of undergraduate students in understanding and reasoning of the phylogenetic tree. The research method is the descriptive method. Students are given multiple choice questions and an essay that representative by tree thinking elements. Each correct answer made percentages. Each student is also given questionnaires. The results showed that the undergraduate students’ initial ability in understanding and reasoning phylogenetic tree is low. Many students are not able to answer questions about the phylogenetic tree. Only 19 % undergraduate student who answered correctly on indicator evaluate the evolutionary relationship among taxa, 25% undergraduate student who answered correctly on indicator applying concepts of the clade, 17% undergraduate student who answered correctly on indicator determines the character evolution, and only a few undergraduate student who can construct the phylogenetic tree.

Improved Maximum Parsimony Models for Phylogenetic Networks.

Science.gov (United States)

Van Iersel, Leo; Jones, Mark; Scornavacca, Celine

2018-05-01

Phylogenetic networks are well suited to represent evolutionary histories comprising reticulate evolution. Several methods aiming at reconstructing explicit phylogenetic networks have been developed in the last two decades. In this article, we propose a new definition of maximum parsimony for phylogenetic networks that permits to model biological scenarios that cannot be modeled by the definitions currently present in the literature (namely, the "hardwired" and "softwired" parsimony). Building on this new definition, we provide several algorithmic results that lay the foundations for new parsimony-based methods for phylogenetic network reconstruction.

[SOX10 mutation is relevant to inner ear malformation in patients with Waardenburg syndrome].

Science.gov (United States)

Xu, G Y; Hao, Q Q; Zhong, L L; Ren, W; Yan, Y; Liu, R Y; Li, J N; Guo, W W; Zhao, H; Yang, S M

2016-11-07

Objective: To determine the relevance between the SOX 10 mutation and Waardenburg syndrome (WS) accompanied with inner ear abnormality by analyzing the inner ear imaging results and molecular and genetic results of the WS patients with the SOX 10 mutation. Methods: This study included 36 WS in patients during 2001 and 2015 in the department of otorhinolaryngology head and neck surgery, Chinese Peoples's Liberation Army General Hospital. The condition of the inner ear of each patient was assessed by analyzing HRCT scans of the temporal bone and MRI scans of the brain and internal auditory canal. Meanwhile, the possible pathogenic genes of WS, including SOX10, MITF , and PAX 3, were also screened. Patients were divided into two groups according to SOX 10 mutation.The Fisher accuracy test was used to determine statistical difference of inner ear deformation incidence between the two groups. Results: Among all 36 patients, 12 were found to have inner ear abnormality. Most abnormalities were posterior semicircular canal deformations, some accompanied with cochlear deformation and an enlarged vestibule. Among all patients, 9 patients were SOX 10 heterozygous mutation carriers, among which six showed bilateral inner ear abnormality. Fisher accuracy test results suggested a significant correlation between the SOX 10 mutation and inner ear abnormality in WS patients ( P =0.036). Conclusion: This study found that WS patients with the SOX 10 mutation are more likely to have deformed inner ears when compared to WS patients without the SOX 10 mutation.

Phylogenetic Conflict in Bears Identified by Automated Discovery of Transposable Element Insertions in Low-Coverage Genomes

Science.gov (United States)

Gallus, Susanne; Janke, Axel

2017-01-01

Abstract Phylogenetic reconstruction from transposable elements (TEs) offers an additional perspective to study evolutionary processes. However, detecting phylogenetically informative TE insertions requires tedious experimental work, limiting the power of phylogenetic inference. Here, we analyzed the genomes of seven bear species using high-throughput sequencing data to detect thousands of TE insertions. The newly developed pipeline for TE detection called TeddyPi (TE detection and discovery for Phylogenetic Inference) identified 150,513 high-quality TE insertions in the genomes of ursine and tremarctine bears. By integrating different TE insertion callers and using a stringent filtering approach, the TeddyPi pipeline produced highly reliable TE insertion calls, which were confirmed by extensive in vitro validation experiments. Analysis of single nucleotide substitutions in the flanking regions of the TEs shows that these substitutions correlate with the phylogenetic signal from the TE insertions. Our phylogenomic analyses show that TEs are a major driver of genomic variation in bears and enabled phylogenetic reconstruction of a well-resolved species tree, despite strong signals for incomplete lineage sorting and introgression. The analyses show that the Asiatic black, sun, and sloth bear form a monophyletic clade, in which phylogenetic incongruence originates from incomplete lineage sorting. TeddyPi is open source and can be adapted to various TE and structural variation callers. The pipeline makes it possible to confidently extract thousands of TE insertions even from low-coverage genomes (∼10×) of nonmodel organisms. This opens new possibilities for biologists to study phylogenies and evolutionary processes as well as rates and patterns of (retro-)transposition and structural variation. PMID:28985298

Evolution and maintenance of sexual size dimorphism: Aligning phylogenetic and experimental evidence

Directory of Open Access Journals (Sweden)

Matjaz eKuntner

2014-06-01

Full Text Available Integrating the insights derived from both phylogenetic and experimental approaches offers a more complete understanding of evolutionary patterns and processes, yet it is rarely a feature of investigations of the evolutionary significance of trait variation. We combine these approaches to reinterpret the patterns and processes in the evolution of female biased sexual size dimorphism in Nephilidae, a spider lineage characterized by the most extreme sexual size dimorphism among terrestrial animals. We use a molecular phylogeny to reconstruct the size evolution for each sex and reveal a case of sexually dimorphic gigantism: both sexes steadily outgrow their ancestral sizes, but the female and male slopes differ, and hence sexual size dimorphism steadily increases. A review of the experimental evidence reveals a predominant net selection for large size in both sexes, consistent with the phylogenetic pattern for females but not for males. Thus, while sexual size dimorphism in spiders most likely originates and is maintained by fecundity selection on females, it is unclear what selection pressures prevent males from becoming as large as females. This integrated approach highlights the dangers of inferring evolutionary significance from experimental studies that isolate the effects of single selection pressures.

Including RNA secondary structures improves accuracy and robustness in reconstruction of phylogenetic trees

Directory of Open Access Journals (Sweden)

Dandekar Thomas

2010-01-01

Full Text Available Abstract Background In several studies, secondary structures of ribosomal genes have been used to improve the quality of phylogenetic reconstructions. An extensive evaluation of the benefits of secondary structure, however, is lacking. Results This is the first study to counter this deficiency. We inspected the accuracy and robustness of phylogenetics with individual secondary structures by simulation experiments for artificial tree topologies with up to 18 taxa and for divergency levels in the range of typical phylogenetic studies. We chose the internal transcribed spacer 2 of the ribosomal cistron as an exemplary marker region. Simulation integrated the coevolution process of sequences with secondary structures. Additionally, the phylogenetic power of marker size duplication was investigated and compared with sequence and sequence-structure reconstruction methods. The results clearly show that accuracy and robustness of Neighbor Joining trees are largely improved by structural information in contrast to sequence only data, whereas a doubled marker size only accounts for robustness. Conclusions Individual secondary structures of ribosomal RNA sequences provide a valuable gain of information content that is useful for phylogenetics. Thus, the usage of ITS2 sequence together with secondary structure for taxonomic inferences is recommended. Other reconstruction methods as maximum likelihood, bayesian inference or maximum parsimony may equally profit from secondary structure inclusion. Reviewers This article was reviewed by Shamil Sunyaev, Andrea Tanzer (nominated by Frank Eisenhaber and Eugene V. Koonin. Open peer review Reviewed by Shamil Sunyaev, Andrea Tanzer (nominated by Frank Eisenhaber and Eugene V. Koonin. For the full reviews, please go to the Reviewers' comments section.

A program for verification of phylogenetic network models.

Science.gov (United States)

Gunawan, Andreas D M; Lu, Bingxin; Zhang, Louxin

2016-09-01

Genetic material is transferred in a non-reproductive manner across species more frequently than commonly thought, particularly in the bacteria kingdom. On one hand, extant genomes are thus more properly considered as a fusion product of both reproductive and non-reproductive genetic transfers. This has motivated researchers to adopt phylogenetic networks to study genome evolution. On the other hand, a gene's evolution is usually tree-like and has been studied for over half a century. Accordingly, the relationships between phylogenetic trees and networks are the basis for the reconstruction and verification of phylogenetic networks. One important problem in verifying a network model is determining whether or not certain existing phylogenetic trees are displayed in a phylogenetic network. This problem is formally called the tree containment problem. It is NP-complete even for binary phylogenetic networks. We design an exponential time but efficient method for determining whether or not a phylogenetic tree is displayed in an arbitrary phylogenetic network. It is developed on the basis of the so-called reticulation-visible property of phylogenetic networks. A C-program is available for download on http://www.math.nus.edu.sg/∼matzlx/tcp_package matzlx@nus.edu.sg Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Evolution of specialization: a phylogenetic study of host range in the red milkweed beetle (Tetraopes tetraophthalmus).

Science.gov (United States)

Rasmann, Sergio; Agrawal, Anurag A

2011-06-01

Specialization is common in most lineages of insect herbivores, one of the most diverse groups of organisms on earth. To address how and why specialization is maintained over evolutionary time, we hypothesized that plant defense and other ecological attributes of potential host plants would predict the performance of a specialist root-feeding herbivore (the red milkweed beetle, Tetraopes tetraophthalmus). Using a comparative phylogenetic and functional trait approach, we assessed the determinants of insect host range across 18 species of Asclepias. Larval survivorship decreased with increasing phylogenetic distance from the true host, Asclepias syriaca, suggesting that adaptation to plant traits drives specialization. Among several root traits measured, only cardenolides (toxic defense chemicals) correlated with larval survival, and cardenolides also explained the phylogenetic distance effect in phylogenetically controlled multiple regression analyses. Additionally, milkweed species having a known association with other Tetraopes beetles were better hosts than species lacking Tetraopes herbivores, and milkweeds with specific leaf area values (a trait related to leaf function and habitat affiliation) similar to those of A. syriaca were better hosts than species having divergent values. We thus conclude that phylogenetic distance is an integrated measure of phenotypic and ecological attributes of Asclepias species, especially defensive cardenolides, which can be used to explain specialization and constraints on host shifts over evolutionary time.

Comparative analyses of plastid genomes from fourteen Cornales species: inferences for phylogenetic relationships and genome evolution.

Science.gov (United States)

Fu, Chao-Nan; Li, Hong-Tao; Milne, Richard; Zhang, Ting; Ma, Peng-Fei; Yang, Jing; Li, De-Zhu; Gao, Lian-Ming

2017-12-08

The Cornales is the basal lineage of the asterids, the largest angiosperm clade. Phylogenetic relationships within the order were previously not fully resolved. Fifteen plastid genomes representing 14 species, ten genera and seven families of Cornales were newly sequenced for comparative analyses of genome features, evolution, and phylogenomics based on different partitioning schemes and filtering strategies. All plastomes of the 14 Cornales species had the typical quadripartite structure with a genome size ranging from 156,567 bp to 158,715 bp, which included two inverted repeats (25,859-26,451 bp) separated by a large single-copy region (86,089-87,835 bp) and a small single-copy region (18,250-18,856 bp) region. These plastomes encoded the same set of 114 unique genes including 31 transfer RNA, 4 ribosomal RNA and 79 coding genes, with an identical gene order across all examined Cornales species. Two genes (rpl22 and ycf15) contained premature stop codons in seven and five species respectively. The phylogenetic relationships among all sampled species were fully resolved with maximum support. Different filtering strategies (none, light and strict) of sequence alignment did not have an effect on these relationships. The topology recovered from coding and noncoding data sets was the same as for the whole plastome, regardless of filtering strategy. Moreover, mutational hotspots and highly informative regions were identified. Phylogenetic relationships among families and intergeneric relationships within family of Cornales were well resolved. Different filtering strategies and partitioning schemes do not influence the relationships. Plastid genomes have great potential to resolve deep phylogenetic relationships of plants.

Isocitrate dehydrogenase mutation hot spots in acute lymphoblastic leukemia and oral cancer

Directory of Open Access Journals (Sweden)

Jen-Yang Tang

2012-03-01

Full Text Available Isocitrate dehydrogenase (IDH encodes a nicotinamide adenine dinucleotide phosphate+-dependent enzyme for oxidative decarboxylation of isocitrate and has an essential role in the tricarboxylic acid cycle. Mutations of IDH1 and IDH2 have been identified in patients with glioma, leukemia, and other cancers. However, the incidence of IDH mutations in acute myeloid leukemia in Taiwan is much lower than that reported in Western countries. The reason for the difference is unknown and its clinical implications remain unclear. Acute lymphoblastic leukemia (ALL is a heterogenous hematopoietic malignancy. Oral squamous cell carcinoma (OSCC results from chronic carcinogen exposures and is highly prevalent in trucking workers, especially in southern Taiwan. Subtypes of both diseases require specific treatments, and molecular markers for developing tailored treatments are limited. High-resolution melting (HRM analysis is now a widely used methodology for rapid, accurate, and low-cost mutation scanning. In this study, 90 adults with OSC and 31 children with ALL were scanned by HRM analysis for IDH1 and IDH2 mutation hot spots. In ALL, the allele frequency was 3.23% in both IDH1 and IDH2. In OSCC, the allele frequency was 2.22% in IDH2. A synonymous mutation over pG313 (c.939A > G of IDH2 was found in both pediatric ALL and adult OSCC. Therefore, we concluded that mutations of IDH are uncommon in ALL and OSCC and are apparently not a major consideration when selecting treatment modalities.

Large-Scale Genomic Analysis of Codon Usage in Dengue Virus and Evaluation of Its Phylogenetic Dependence

Science.gov (United States)

Lara-Ramírez, Edgar E.; Salazar, Ma Isabel; López-López, María de Jesús; Salas-Benito, Juan Santiago; Sánchez-Varela, Alejandro

2014-01-01

The increasing number of dengue virus (DENV) genome sequences available allows identifying the contributing factors to DENV evolution. In the present study, the codon usage in serotypes 1–4 (DENV1–4) has been explored for 3047 sequenced genomes using different statistics methods. The correlation analysis of total GC content (GC) with GC content at the three nucleotide positions of codons (GC1, GC2, and GC3) as well as the effective number of codons (ENC, ENCp) versus GC3 plots revealed mutational bias and purifying selection pressures as the major forces influencing the codon usage, but with distinct pressure on specific nucleotide position in the codon. The correspondence analysis (CA) and clustering analysis on relative synonymous codon usage (RSCU) within each serotype showed similar clustering patterns to the phylogenetic analysis of nucleotide sequences for DENV1–4. These clustering patterns are strongly related to the virus geographic origin. The phylogenetic dependence analysis also suggests that stabilizing selection acts on the codon usage bias. Our analysis of a large scale reveals new feature on DENV genomic evolution. PMID:25136631

Integrating Taxonomic, Functional and Phylogenetic Beta Diversities: Interactive Effects with the Biome and Land Use across Taxa.

Science.gov (United States)

Corbelli, Julian Martin; Zurita, Gustavo Andres; Filloy, Julieta; Galvis, Juan Pablo; Vespa, Natalia Isabel; Bellocq, Isabel

2015-01-01

The spatial distribution of species, functional traits and phylogenetic relationships at both the regional and local scales provide complementary approaches to study patterns of biodiversity and help to untangle the mechanisms driving community assembly. Few studies have simultaneously considered the taxonomic (TBD), functional (FBD) and phylogenetic (PBD) facets of beta diversity. Here we analyze the associations between TBD, FBD, and PBD with the biome (representing different regional species pools) and land use, and investigate whether TBD, FBD and PBD were correlated. In the study design we considered two widely used indicator taxa (birds and ants) from two contrasting biomes (subtropical forest and grassland) and land uses (tree plantations and cropfields) in the southern Neotropics. Non-metric multidimensional scaling showed that taxonomic, functional and phylogenetic distances were associated to biome and land use; study sites grouped into four groups on the bi-dimensional space (cropfields in forest and grassland, and tree plantations in forest and grassland), and that was consistent across beta diversity facets and taxa. Mantel and PERMANOVA tests showed that TBD, FBD and PBD were positively correlated for both bird and ant assemblages; in general, partial correlations were also significant. Some of the functional traits considered here were conserved along phylogeny. Our results will contribute to the development of sound land use planning and beta diversity conservation.

Integrating Taxonomic, Functional and Phylogenetic Beta Diversities: Interactive Effects with the Biome and Land Use across Taxa

Science.gov (United States)

Corbelli, Julian Martin; Zurita, Gustavo Andres; Filloy, Julieta; Galvis, Juan Pablo; Vespa, Natalia Isabel; Bellocq, Isabel

2015-01-01

The spatial distribution of species, functional traits and phylogenetic relationships at both the regional and local scales provide complementary approaches to study patterns of biodiversity and help to untangle the mechanisms driving community assembly. Few studies have simultaneously considered the taxonomic (TBD), functional (FBD) and phylogenetic (PBD) facets of beta diversity. Here we analyze the associations between TBD, FBD, and PBD with the biome (representing different regional species pools) and land use, and investigate whether TBD, FBD and PBD were correlated. In the study design we considered two widely used indicator taxa (birds and ants) from two contrasting biomes (subtropical forest and grassland) and land uses (tree plantations and cropfields) in the southern Neotropics. Non-metric multidimensional scaling showed that taxonomic, functional and phylogenetic distances were associated to biome and land use; study sites grouped into four groups on the bi-dimensional space (cropfields in forest and grassland, and tree plantations in forest and grassland), and that was consistent across beta diversity facets and taxa. Mantel and PERMANOVA tests showed that TBD, FBD and PBD were positively correlated for both bird and ant assemblages; in general, partial correlations were also significant. Some of the functional traits considered here were conserved along phylogeny. Our results will contribute to the development of sound land use planning and beta diversity conservation. PMID:25978319

Integrating Taxonomic, Functional and Phylogenetic Beta Diversities: Interactive Effects with the Biome and Land Use across Taxa.

Directory of Open Access Journals (Sweden)

Julian Martin Corbelli

Full Text Available The spatial distribution of species, functional traits and phylogenetic relationships at both the regional and local scales provide complementary approaches to study patterns of biodiversity and help to untangle the mechanisms driving community assembly. Few studies have simultaneously considered the taxonomic (TBD, functional (FBD and phylogenetic (PBD facets of beta diversity. Here we analyze the associations between TBD, FBD, and PBD with the biome (representing different regional species pools and land use, and investigate whether TBD, FBD and PBD were correlated. In the study design we considered two widely used indicator taxa (birds and ants from two contrasting biomes (subtropical forest and grassland and land uses (tree plantations and cropfields in the southern Neotropics. Non-metric multidimensional scaling showed that taxonomic, functional and phylogenetic distances were associated to biome and land use; study sites grouped into four groups on the bi-dimensional space (cropfields in forest and grassland, and tree plantations in forest and grassland, and that was consistent across beta diversity facets and taxa. Mantel and PERMANOVA tests showed that TBD, FBD and PBD were positively correlated for both bird and ant assemblages; in general, partial correlations were also significant. Some of the functional traits considered here were conserved along phylogeny. Our results will contribute to the development of sound land use planning and beta diversity conservation.

Low Genetic Quality Alters Key Dimensions of the Mutational Spectrum.

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Nathaniel P Sharp

2016-03-01

Full Text Available Mutations affect individual health, population persistence, adaptation, diversification, and genome evolution. There is evidence that the mutation rate varies among genotypes, but the causes of this variation are poorly understood. Here, we link differences in genetic quality with variation in spontaneous mutation in a Drosophila mutation accumulation experiment. We find that chromosomes maintained in low-quality genetic backgrounds experience a higher rate of indel mutation and a lower rate of gene conversion in a manner consistent with condition-based differences in the mechanisms used to repair DNA double strand breaks. These aspects of the mutational spectrum were also associated with body mass, suggesting that the effect of genetic quality on DNA repair was mediated by overall condition, and providing a mechanistic explanation for the differences in mutational fitness decline among these genotypes. The rate and spectrum of substitutions was unaffected by genetic quality, but we find variation in the probability of substitutions and indels with respect to several aspects of local sequence context, particularly GC content, with implications for models of molecular evolution and genome scans for signs of selection. Our finding that the chances of mutation depend on genetic context and overall condition has important implications for how sequences evolve, the risk of extinction, and human health.

Conservation Action Based on Threatened Species Capture Taxonomic and Phylogenetic Richness in Breeding and Wintering Populations of Central Asian Birds

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Schweizer, Manuel; Ayé, Raffael; Kashkarov, Roman; Roth, Tobias

2014-01-01

Although phylogenetic diversity has been suggested to be relevant from a conservation point of view, its role is still limited in applied nature conservation. Recently, the practice of investing conservation resources based on threatened species was identified as a reason for the slow integration of phylogenetic diversity in nature conservation planning. One of the main arguments is based on the observation that threatened species are not evenly distributed over the phylogenetic tree. However this argument seems to dismiss the fact that conservation action is a spatially explicit process, and even if threatened species are not evenly distributed over the phylogenetic tree, the occurrence of threatened species could still indicate areas with above average phylogenetic diversity and consequently could protect phylogenetic diversity. Here we aim to study the selection of important bird areas in Central Asia, which were nominated largely based on the presence of threatened bird species. We show that although threatened species occurring in Central Asia do not capture phylogenetically more distinct species than expected by chance, the current spatially explicit conservation approach of selecting important bird areas covers above average taxonomic and phylogenetic diversity of breeding and wintering birds. We conclude that the spatially explicit processes of conservation actions need to be considered in the current discussion of whether new prioritization methods are needed to complement conservation action based on threatened species. PMID:25337861

Rearrangement moves on rooted phylogenetic networks.

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Gambette, Philippe; van Iersel, Leo; Jones, Mark; Lafond, Manuel; Pardi, Fabio; Scornavacca, Celine

2017-08-01

Phylogenetic tree reconstruction is usually done by local search heuristics that explore the space of the possible tree topologies via simple rearrangements of their structure. Tree rearrangement heuristics have been used in combination with practically all optimization criteria in use, from maximum likelihood and parsimony to distance-based principles, and in a Bayesian context. Their basic components are rearrangement moves that specify all possible ways of generating alternative phylogenies from a given one, and whose fundamental property is to be able to transform, by repeated application, any phylogeny into any other phylogeny. Despite their long tradition in tree-based phylogenetics, very little research has gone into studying similar rearrangement operations for phylogenetic network-that is, phylogenies explicitly representing scenarios that include reticulate events such as hybridization, horizontal gene transfer, population admixture, and recombination. To fill this gap, we propose "horizontal" moves that ensure that every network of a certain complexity can be reached from any other network of the same complexity, and "vertical" moves that ensure reachability between networks of different complexities. When applied to phylogenetic trees, our horizontal moves-named rNNI and rSPR-reduce to the best-known moves on rooted phylogenetic trees, nearest-neighbor interchange and rooted subtree pruning and regrafting. Besides a number of reachability results-separating the contributions of horizontal and vertical moves-we prove that rNNI moves are local versions of rSPR moves, and provide bounds on the sizes of the rNNI neighborhoods. The paper focuses on the most biologically meaningful versions of phylogenetic networks, where edges are oriented and reticulation events clearly identified. Moreover, our rearrangement moves are robust to the fact that networks with higher complexity usually allow a better fit with the data. Our goal is to provide a solid basis for

Rearrangement moves on rooted phylogenetic networks.

Directory of Open Access Journals (Sweden)

Philippe Gambette

2017-08-01

Full Text Available Phylogenetic tree reconstruction is usually done by local search heuristics that explore the space of the possible tree topologies via simple rearrangements of their structure. Tree rearrangement heuristics have been used in combination with practically all optimization criteria in use, from maximum likelihood and parsimony to distance-based principles, and in a Bayesian context. Their basic components are rearrangement moves that specify all possible ways of generating alternative phylogenies from a given one, and whose fundamental property is to be able to transform, by repeated application, any phylogeny into any other phylogeny. Despite their long tradition in tree-based phylogenetics, very little research has gone into studying similar rearrangement operations for phylogenetic network-that is, phylogenies explicitly representing scenarios that include reticulate events such as hybridization, horizontal gene transfer, population admixture, and recombination. To fill this gap, we propose "horizontal" moves that ensure that every network of a certain complexity can be reached from any other network of the same complexity, and "vertical" moves that ensure reachability between networks of different complexities. When applied to phylogenetic trees, our horizontal moves-named rNNI and rSPR-reduce to the best-known moves on rooted phylogenetic trees, nearest-neighbor interchange and rooted subtree pruning and regrafting. Besides a number of reachability results-separating the contributions of horizontal and vertical moves-we prove that rNNI moves are local versions of rSPR moves, and provide bounds on the sizes of the rNNI neighborhoods. The paper focuses on the most biologically meaningful versions of phylogenetic networks, where edges are oriented and reticulation events clearly identified. Moreover, our rearrangement moves are robust to the fact that networks with higher complexity usually allow a better fit with the data. Our goal is to provide

Phylogenetic search through partial tree mixing

Science.gov (United States)

2012-01-01

Background Recent advances in sequencing technology have created large data sets upon which phylogenetic inference can be performed. Current research is limited by the prohibitive time necessary to perform tree search on a reasonable number of individuals. This research develops new phylogenetic algorithms that can operate on tens of thousands of species in a reasonable amount of time through several innovative search techniques. Results When compared to popular phylogenetic search algorithms, better trees are found much more quickly for large data sets. These algorithms are incorporated in the PSODA application available at http://dna.cs.byu.edu/psoda Conclusions The use of Partial Tree Mixing in a partition based tree space allows the algorithm to quickly converge on near optimal tree regions. These regions can then be searched in a methodical way to determine the overall optimal phylogenetic solution. PMID:23320449

Phylogenetic relationships in Solanaceae and related species based on cpDNA sequence from plastid trnE-trnT region

Directory of Open Access Journals (Sweden)

Danila Montewka Melotto-Passarin

2008-01-01

Full Text Available Intergenic spacers of chloroplast DNA (cpDNA are very useful in phylogenetic and population genetic studiesof plant species, to study their potential integration in phylogenetic analysis. The non-coding trnE-trnT intergenic spacer ofcpDNA was analyzed to assess the nucleotide sequence polymorphism of 16 Solanaceae species and to estimate its ability tocontribute to the resolution of phylogenetic studies of this group. Multiple alignments of DNA sequences of trnE-trnT intergenicspacer made the identification of nucleotide variability in this region possible and the phylogeny was estimated by maximumparsimony and rooted with Convolvulaceae Ipomoea batatas, the most closely related family. Besides, this intergenic spacerwas tested for the phylogenetic ability to differentiate taxonomic levels. For this purpose, species from four other families wereanalyzed and compared with Solanaceae species. Results confirmed polymorphism in the trnE-trnT region at different taxonomiclevels.

Phylogenetic Signal in AFLP Data Sets

NARCIS (Netherlands)

Koopman, W.J.M.

2005-01-01

AFLP markers provide a potential source of phylogenetic information for molecular systematic studies. However, there are properties of restriction fragment data that limit phylogenetic interpretation of AFLPs. These are (a) possible nonindependence of fragments, (b) problems of homology assignment

High-resolution melting (HRM) assay for the detection of recurrent BRCA1/BRCA2 germline mutations in Tunisian breast/ovarian cancer families.

Science.gov (United States)

Riahi, Aouatef; Kharrat, Maher; Lariani, Imen; Chaabouni-Bouhamed, Habiba

2014-12-01

Germline deleterious mutations in the BRCA1/BRCA2 genes are associated with an increased risk for the development of breast and ovarian cancer. Given the large size of these genes the detection of such mutations represents a considerable technical challenge. Therefore, the development of cost-effective and rapid methods to identify these mutations became a necessity. High resolution melting analysis (HRM) is a rapid and efficient technique extensively employed as high-throughput mutation scanning method. The purpose of our study was to assess the specificity and sensitivity of HRM for BRCA1 and BRCA2 genes scanning. As a first step we estimate the ability of HRM for detection mutations in a set of 21 heterozygous samples harboring 8 different known BRCA1/BRCA2 variations, all samples had been preliminarily investigated by direct sequencing, and then we performed a blinded analysis by HRM in a set of 68 further sporadic samples of unknown genotype. All tested heterozygous BRCA1/BRCA2 variants were easily identified. However the HRM assay revealed further alteration that we initially had not searched (one unclassified variant). Furthermore, sequencing confirmed all the HRM detected mutations in the set of unknown samples, including homozygous changes, indicating that in this cohort, with the optimized assays, the mutations detections sensitivity and specificity were 100 %. HRM is a simple, rapid and efficient scanning method for known and unknown BRCA1/BRCA2 germline mutations. Consequently the method will allow for the economical screening of recurrent mutations in Tunisian population.

Molecular evolution of ependymin and the phylogenetic resolution of early divergences among euteleost fishes.

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Ortí, G; Meyer, A

1996-04-01

The rate and pattern of DNA evolution of ependymin, a single-copy gene coding for a highly expressed glycoprotein in the brain matrix of teleost fishes, is characterized and its phylogenetic utility for fish systematics is assessed. DNA sequences were determined from catfish, electric fish, and characiforms and compared with published ependymin sequences from cyprinids, salmon, pike, and herring. Among these groups, ependymin amino acid sequences were highly divergent (up to 60% sequence difference), but had surprisingly similar hydropathy profiles and invariant glycosylation sites, suggesting that functional properties of the proteins are conserved. Comparison of base composition at third codon positions and introns revealed AT-rich introns and GC-rich third codon positions, suggesting that the biased codon usage observed might not be due to mutational bias. Phylogenetic information content of third codon positions was surprisingly high and sufficient to recover the most basal nodes of the tree, in spite of the observation that pairwise distances (at third codon positions) were well above the presumed saturation level. This finding can be explained by the high proportion of phylogenetically informative nonsynonymous changes at third codon positions among these highly divergent proteins. Ependymin DNA sequences have established the first molecular evidence for the monophyly of a group containing salmonids and esociforms. In addition, ependymin suggests a sister group relationship of electric fish (Gymnotiformes) and Characiformes, constituting a significant departure from currently accepted classifications. However, relationships among characiform lineages were not completely resolved by ependymin sequences in spite of seemingly appropriate levels of variation among taxa and considerably low levels of homoplasy in the data (consistency index = 0.7). If the diversification of Characiformes took place in an "explosive" manner, over a relatively short period of time

Phylogenetic reconstruction methods: an overview.

Science.gov (United States)

De Bruyn, Alexandre; Martin, Darren P; Lefeuvre, Pierre

2014-01-01

Initially designed to infer evolutionary relationships based on morphological and physiological characters, phylogenetic reconstruction methods have greatly benefited from recent developments in molecular biology and sequencing technologies with a number of powerful methods having been developed specifically to infer phylogenies from macromolecular data. This chapter, while presenting an overview of basic concepts and methods used in phylogenetic reconstruction, is primarily intended as a simplified step-by-step guide to the construction of phylogenetic trees from nucleotide sequences using fairly up-to-date maximum likelihood methods implemented in freely available computer programs. While the analysis of chloroplast sequences from various Vanilla species is used as an illustrative example, the techniques covered here are relevant to the comparative analysis of homologous sequences datasets sampled from any group of organisms.

Application of Integrated Photogrammetric and Terrestrial Laser Scanning Data to Cultural Heritage Surveying

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Klapa, Przemyslaw; Mitka, Bartosz; Zygmunt, Mariusz

2017-12-01

The terrestrial laser scanning technology has a wide spectrum of applications, from land surveying, civil engineering and architecture to archaeology. The technology is capable of obtaining, in a short time, accurate coordinates of points which represent the surface of objects. Scanning of buildings is therefore a process which ensures obtaining information on all structural elements a building. The result is a point cloud consisting of millions of elements which are a perfect source of information on the object and its surrounding. The photogrammetric techniques allow documenting an object in high resolution in the form of orthophoto plans, or are a basis to develop 2D documentation or obtain point clouds for objects and 3D modelling. Integration of photogrammetric data and TLS brings a new quality in surveying historic monuments. Historic monuments play an important cultural and historical role. Centuries-old buildings require constant renovation and preservation of their structural and visual invariability while maintaining safety of people who use them. The full process of surveying allows evaluating the actual condition of monuments and planning repairs and renovations. Huge sizes and specific types of historic monuments cause problems in obtaining reliable and full information on them. The TLS technology allows obtaining such information in a short time and is non-invasive. A point cloud is not only a basis for developing architectural and construction documentation or evaluation of actual condition of a building. It also is a real visualization of monuments and their entire environment. The saved image of object surface can be presented at any time and place. A cyclical TLS survey of historic monuments allows detecting structural changes and evaluating damage and changes that cause deformation of monument’s components. The paper presents application of integrated photogrammetric data and TLS illustrated on an example of historic monuments from southern

Phylogenetic Conflict in Bears Identified by Automated Discovery of Transposable Element Insertions in Low-Coverage Genomes.

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Lammers, Fritjof; Gallus, Susanne; Janke, Axel; Nilsson, Maria A

2017-10-01

Phylogenetic reconstruction from transposable elements (TEs) offers an additional perspective to study evolutionary processes. However, detecting phylogenetically informative TE insertions requires tedious experimental work, limiting the power of phylogenetic inference. Here, we analyzed the genomes of seven bear species using high-throughput sequencing data to detect thousands of TE insertions. The newly developed pipeline for TE detection called TeddyPi (TE detection and discovery for Phylogenetic Inference) identified 150,513 high-quality TE insertions in the genomes of ursine and tremarctine bears. By integrating different TE insertion callers and using a stringent filtering approach, the TeddyPi pipeline produced highly reliable TE insertion calls, which were confirmed by extensive in vitro validation experiments. Analysis of single nucleotide substitutions in the flanking regions of the TEs shows that these substitutions correlate with the phylogenetic signal from the TE insertions. Our phylogenomic analyses show that TEs are a major driver of genomic variation in bears and enabled phylogenetic reconstruction of a well-resolved species tree, despite strong signals for incomplete lineage sorting and introgression. The analyses show that the Asiatic black, sun, and sloth bear form a monophyletic clade, in which phylogenetic incongruence originates from incomplete lineage sorting. TeddyPi is open source and can be adapted to various TE and structural variation callers. The pipeline makes it possible to confidently extract thousands of TE insertions even from low-coverage genomes (∼10×) of nonmodel organisms. This opens new possibilities for biologists to study phylogenies and evolutionary processes as well as rates and patterns of (retro-)transposition and structural variation. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Integrated fringe projection 3D scanning system for large-scale metrology based on laser tracker

Science.gov (United States)

Du, Hui; Chen, Xiaobo; Zhou, Dan; Guo, Gen; Xi, Juntong

2017-10-01

Large scale components exist widely in advance manufacturing industry,3D profilometry plays a pivotal role for the quality control. This paper proposes a flexible, robust large-scale 3D scanning system by integrating a robot with a binocular structured light scanner and a laser tracker. The measurement principle and system construction of the integrated system are introduced. And a mathematical model is established for the global data fusion. Subsequently, a flexible and robust method and mechanism is introduced for the establishment of the end coordination system. Based on this method, a virtual robot noumenon is constructed for hand-eye calibration. And then the transformation matrix between end coordination system and world coordination system is solved. Validation experiment is implemented for verifying the proposed algorithms. Firstly, hand-eye transformation matrix is solved. Then a car body rear is measured for 16 times for the global data fusion algorithm verification. And the 3D shape of the rear is reconstructed successfully.

Phylogenetic analysis of molecular and morphological data highlights uncertainty in the relationships of fossil and living species of Elopomorpha (Actinopterygii: Teleostei).

Science.gov (United States)

Dornburg, Alex; Friedman, Matt; Near, Thomas J

2015-08-01

Elopomorpha is one of the three main clades of living teleost fishes and includes a range of disparate lineages including eels, tarpons, bonefishes, and halosaurs. Elopomorphs were among the first groups of fishes investigated using Hennigian phylogenetic methods and continue to be the object of intense phylogenetic scrutiny due to their economic significance, diversity, and crucial evolutionary status as the sister group of all other teleosts. While portions of the phylogenetic backbone for Elopomorpha are consistent between studies, the relationships among Albula, Pterothrissus, Notacanthiformes, and Anguilliformes remain contentious and difficult to evaluate. This lack of phylogenetic resolution is problematic as fossil lineages are often described and placed taxonomically based on an assumed sister group relationship between Albula and Pterothrissus. In addition, phylogenetic studies using morphological data that sample elopomorph fossil lineages often do not include notacanthiform or anguilliform lineages, potentially introducing a bias toward interpreting fossils as members of the common stem of Pterothrissus and Albula. Here we provide a phylogenetic analysis of DNA sequences sampled from multiple nuclear genes that include representative taxa from Albula, Pterothrissus, Notacanthiformes and Anguilliformes. We integrate our molecular dataset with a morphological character matrix that spans both living and fossil elopomorph lineages. Our results reveal substantial uncertainty in the placement of Pterothrissus as well as all sampled fossil lineages, questioning the stability of the taxonomy of fossil Elopomorpha. However, despite topological uncertainty, our integration of fossil lineages into a Bayesian time calibrated framework provides divergence time estimates for the clade that are consistent with previously published age estimates based on the elopomorph fossil record and molecular estimates resulting from traditional node-dating methods. Copyright �

Towards linked open gene mutations data

Science.gov (United States)

2012-01-01

Background With the advent of high-throughput technologies, a great wealth of variation data is being produced. Such information may constitute the basis for correlation analyses between genotypes and phenotypes and, in the future, for personalized medicine. Several databases on gene variation exist, but this kind of information is still scarce in the Semantic Web framework. In this paper, we discuss issues related to the integration of mutation data in the Linked Open Data infrastructure, part of the Semantic Web framework. We present the development of a mapping from the IARC TP53 Mutation database to RDF and the implementation of servers publishing this data. Methods A version of the IARC TP53 Mutation database implemented in a relational database was used as first test set. Automatic mappings to RDF were first created by using D2RQ and later manually refined by introducing concepts and properties from domain vocabularies and ontologies, as well as links to Linked Open Data implementations of various systems of biomedical interest. Since D2RQ query performances are lower than those that can be achieved by using an RDF archive, generated data was also loaded into a dedicated system based on tools from the Jena software suite. Results We have implemented a D2RQ Server for TP53 mutation data, providing data on a subset of the IARC database, including gene variations, somatic mutations, and bibliographic references. The server allows to browse the RDF graph by using links both between classes and to external systems. An alternative interface offers improved performances for SPARQL queries. The resulting data can be explored by using any Semantic Web browser or application. Conclusions This has been the first case of a mutation database exposed as Linked Data. A revised version of our prototype, including further concepts and IARC TP53 Mutation database data sets, is under development. The publication of variation information as Linked Data opens new perspectives

Towards linked open gene mutations data.

Science.gov (United States)

Zappa, Achille; Splendiani, Andrea; Romano, Paolo

2012-03-28

With the advent of high-throughput technologies, a great wealth of variation data is being produced. Such information may constitute the basis for correlation analyses between genotypes and phenotypes and, in the future, for personalized medicine. Several databases on gene variation exist, but this kind of information is still scarce in the Semantic Web framework. In this paper, we discuss issues related to the integration of mutation data in the Linked Open Data infrastructure, part of the Semantic Web framework. We present the development of a mapping from the IARC TP53 Mutation database to RDF and the implementation of servers publishing this data. A version of the IARC TP53 Mutation database implemented in a relational database was used as first test set. Automatic mappings to RDF were first created by using D2RQ and later manually refined by introducing concepts and properties from domain vocabularies and ontologies, as well as links to Linked Open Data implementations of various systems of biomedical interest. Since D2RQ query performances are lower than those that can be achieved by using an RDF archive, generated data was also loaded into a dedicated system based on tools from the Jena software suite. We have implemented a D2RQ Server for TP53 mutation data, providing data on a subset of the IARC database, including gene variations, somatic mutations, and bibliographic references. The server allows to browse the RDF graph by using links both between classes and to external systems. An alternative interface offers improved performances for SPARQL queries. The resulting data can be explored by using any Semantic Web browser or application. This has been the first case of a mutation database exposed as Linked Data. A revised version of our prototype, including further concepts and IARC TP53 Mutation database data sets, is under development.The publication of variation information as Linked Data opens new perspectives: the exploitation of SPARQL searches on

A novel mutation in PAX3 associated with Waardenburg syndrome type I in a Chinese family.

Science.gov (United States)

Xiao, Yun; Luo, Jianfen; Zhang, Fengguo; Li, Jianfeng; Han, Yuechen; Zhang, Daogong; Wang, Mingming; Ma, Yalin; Xu, Lei; Bai, Xiaohui; Wang, Haibo

2016-01-01

The novel compound heterozygous mutation in PAX3 was the key genetic reason for WS1 in this family, which was useful to the molecular diagnosis of WS1. Screening the pathogenic mutations in a four generation Chinese family with Waardenburg syndrome type I (WS1). WS1 was diagnosed in a 4-year-old boy according to the Waardenburg syndrome Consortium criteria. The detailed family history revealed four affected members in the family. Routine clinical, audiological examination, and ophthalmologic evaluation were performed on four affected and 10 healthy members in this family. The genetic analysis was conducted, including the targeted next-generation sequencing of 127 known deafness genes combined with Sanger sequencing, TA clone and bioinformatic analysis. A novel compound heterozygous mutation c.[169_170insC;172_174delAAG] (p.His57ProfsX55) was identified in PAX3, which was co-segregated with WS1 in the Chinese family. This mutation was absent in the unaffected family members and 200 ethnicity-matched controls. The phylogenetic analysis and three-dimensional (3D) modeling of Pax3 protein further confirmed that the novel compound heterozygous mutation was pathogenic.

Discovery of Point Mutations in the Voltage-Gated Sodium Channel from African Aedes aegypti Populations: Potential Phylogenetic Reasons for Gene Introgression

Science.gov (United States)

Muranami, Yuto; Kawashima, Emiko; Osei, Joseph H. N.; Sakyi, Kojo Yirenkyi; Dadzie, Samuel; de Souza, Dziedzom K.; Appawu, Maxwell; Ohta, Nobuo; Minakawa, Noboru

2016-01-01

Background Yellow fever is endemic in some countries in Africa, and Aedes aegpyti is one of the most important vectors implicated in the outbreak. The mapping of the nation-wide distribution and the detection of insecticide resistance of vector mosquitoes will provide the beneficial information for forecasting of dengue and yellow fever outbreaks and effective control measures. Methodology/Principal Findings High resistance to DDT was observed in all mosquito colonies collected in Ghana. The resistance and the possible existence of resistance or tolerance to permethrin were suspected in some colonies. High frequencies of point mutations at the voltage-gated sodium channel (F1534C) and one heterozygote of the other mutation (V1016I) were detected, and this is the first detection on the African continent. The frequency of F1534C allele and the ratio of F1534C homozygotes in Ae. aegypti aegypti (Aaa) were significantly higher than those in Ae. aegypti formosus (Aaf). We could detect the two types of introns between exon 20 and 21, and the F1534C mutations were strongly linked with one type of intron, which was commonly found in South East Asian and South and Central American countries, suggesting the possibility that this mutation was introduced from other continents or convergently selected after the introgression of Aaa genes from the above area. Conclusions/Significance The worldwide eradication programs in 1940s and 1950s might have caused high selection pressure on the mosquito populations and expanded the distribution of insecticide-resistant Ae. aegypti populations. Selection of the F1534C point mutation could be hypothesized to have taken place during this period. The selection of the resistant population of Ae. aegypti with the point mutation of F1534C, and the worldwide transportation of vector mosquitoes in accordance with human activity such as trading of used tires, might result in the widespread distribution of F1534C point mutation in tropical countries

Nucleotide diversity and phylogenetic relationships among ...

Indian Academy of Sciences (India)

NIRAJ SINGH

for phylogenetic analysis of Gladiolus and related taxa using combined datasets from chloroplast genome. The psbA–trnH ... phylogenetic relationships among cultivars could be useful for hybridization programmes for further improvement of the crop. [Singh N. ... breeding in nature, and exhibited diverse pollination mech-.

Mutation spectrum of 122 hemophilia A families from Taiwanese population by LD-PCR, DHPLC, multiplex PCR and evaluating the clinical application of HRM

Directory of Open Access Journals (Sweden)

Chang Chieh-Ting

2008-06-01

Full Text Available Abstract Background Hemophilia A represents the most common and severe inherited hemorrhagic disorder. It is caused by mutations in the F8 gene, which leads to a deficiency or dysfunctional factor VIII protein, an essential cofactor in the factor X activation complex. Methods We used long-distance polymerase chain reaction and denaturing high performance liquid chromatography for mutation scanning of the F8 gene. We designed the competitive multiplex PCR to identify the carrier with exonal deletions. In order to facilitate throughput and minimize the cost of mutation scanning, we also evaluated a new mutation scanning technique, high resolution melting analysis (HRM, as an alternative screening method. Results We presented the results of detailed screening of 122 Taiwanese families with hemophilia A and reported twenty-nine novel mutations. There was one family identified with whole exons deletion, and the carriers were successfully recognized by multiplex PCR. By HRM, the different melting curve patterns were easily identified in 25 out of 28 cases (89% and 15 out of 15 (100% carriers. The sensitivity was 93 % (40/43. The overall mutation detection rate of hemophilia A was 100% in this study. Conclusion We proposed a diagnostic strategy for hemophilia A genetic diagnosis. We consider HRM as a powerful screening tool that would provide us with a more cost-effective protocol for hemophilia A mutation identification.

Mutation analysis of 2009 pandemic influenza A(H1N1 viruses collected in Japan during the peak phase of the pandemic.

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Jean-Étienne Morlighem

Full Text Available BACKGROUND: Pandemic influenza A(H1N1 virus infection quickly circulated worldwide in 2009. In Japan, the first case was reported in May 2009, one month after its outbreak in Mexico. Thereafter, A(H1N1 infection spread widely throughout the country. It is of great importance to profile and understand the situation regarding viral mutations and their circulation in Japan to accumulate a knowledge base and to prepare clinical response platforms before a second pandemic (pdm wave emerges. METHODOLOGY: A total of 253 swab samples were collected from patients with influenza-like illness in the Osaka, Tokyo, and Chiba areas both in May 2009 and between October 2009 and January 2010. We analyzed partial sequences of the hemagglutinin (HA and neuraminidase (NA genes of the 2009 pdm influenza virus in the collected clinical samples. By phylogenetic analysis, we identified major variants of the 2009 pdm influenza virus and critical mutations associated with severe cases, including drug-resistance mutations. RESULTS AND CONCLUSIONS: Our sequence analysis has revealed that both HA-S220T and NA-N248D are major non-synonymous mutations that clearly discriminate the 2009 pdm influenza viruses identified in the very early phase (May 2009 from those found in the peak phase (October 2009 to January 2010 in Japan. By phylogenetic analysis, we found 14 micro-clades within the viruses collected during the peak phase. Among them, 12 were new micro-clades, while two were previously reported. Oseltamivir resistance-related mutations, i.e., NA-H275Y and NA-N295S, were also detected in sporadic cases in Osaka and Tokyo.

Determinants of plant community assembly in a mosaic of landscape units in central Amazonia: ecological and phylogenetic perspectives.

Directory of Open Access Journals (Sweden)

María Natalia Umaña

Full Text Available The Amazon harbours one of the richest ecosystems on Earth. Such diversity is likely to be promoted by plant specialization, associated with the occurrence of a mosaic of landscape units. Here, we integrate ecological and phylogenetic data at different spatial scales to assess the importance of habitat specialization in driving compositional and phylogenetic variation across the Amazonian forest. To do so, we evaluated patterns of floristic dissimilarity and phylogenetic turnover, habitat association and phylogenetic structure in three different landscape units occurring in terra firme (Hilly and Terrace and flooded forests (Igapó. We established two 1-ha tree plots in each of these landscape units at the Caparú Biological Station, SW Colombia, and measured edaphic, topographic and light variables. At large spatial scales, terra firme forests exhibited higher levels of species diversity and phylodiversity than flooded forests. These two types of forests showed conspicuous differences in species and phylogenetic composition, suggesting that environmental sorting due to flood is important, and can go beyond the species level. At a local level, landscape units showed floristic divergence, driven both by geographical distance and by edaphic specialization. In terms of phylogenetic structure, Igapó forests showed phylogenetic clustering, whereas Hilly and Terrace forests showed phylogenetic evenness. Within plots, however, local communities did not show any particular trend. Overall, our findings suggest that flooded forests, characterized by stressful environments, impose limits to species occurrence, whereas terra firme forests, more environmentally heterogeneous, are likely to provide a wider range of ecological conditions and therefore to bear higher diversity. Thus, Amazonia should be considered as a mosaic of landscape units, where the strength of habitat association depends upon their environmental properties.

Determinants of Plant Community Assembly in a Mosaic of Landscape Units in Central Amazonia: Ecological and Phylogenetic Perspectives

Science.gov (United States)

Umaña, María Natalia; Norden, Natalia; Cano, Ángela; Stevenson, Pablo R.

2012-01-01

The Amazon harbours one of the richest ecosystems on Earth. Such diversity is likely to be promoted by plant specialization, associated with the occurrence of a mosaic of landscape units. Here, we integrate ecological and phylogenetic data at different spatial scales to assess the importance of habitat specialization in driving compositional and phylogenetic variation across the Amazonian forest. To do so, we evaluated patterns of floristic dissimilarity and phylogenetic turnover, habitat association and phylogenetic structure in three different landscape units occurring in terra firme (Hilly and Terrace) and flooded forests (Igapó). We established two 1-ha tree plots in each of these landscape units at the Caparú Biological Station, SW Colombia, and measured edaphic, topographic and light variables. At large spatial scales, terra firme forests exhibited higher levels of species diversity and phylodiversity than flooded forests. These two types of forests showed conspicuous differences in species and phylogenetic composition, suggesting that environmental sorting due to flood is important, and can go beyond the species level. At a local level, landscape units showed floristic divergence, driven both by geographical distance and by edaphic specialization. In terms of phylogenetic structure, Igapó forests showed phylogenetic clustering, whereas Hilly and Terrace forests showed phylogenetic evenness. Within plots, however, local communities did not show any particular trend. Overall, our findings suggest that flooded forests, characterized by stressful environments, impose limits to species occurrence, whereas terra firme forests, more environmentally heterogeneous, are likely to provide a wider range of ecological conditions and therefore to bear higher diversity. Thus, Amazonia should be considered as a mosaic of landscape units, where the strength of habitat association depends upon their environmental properties. PMID:23028844

A new species of Allodaposuchus (Eusuchia, Crocodylia from the Maastrichtian (Late Cretaceous of Spain: phylogenetic and paleobiological implications

Directory of Open Access Journals (Sweden)

Alejandro Blanco

2015-08-01

Full Text Available Background. The Late Cretaceous is a keystone period to understand the origin and early radiation of Crocodylia, the group containing all extant lineages of crocodilians. Among the taxa described from the latest Cretaceous of Europe, the genus Allodaposuchus is one of the most common but also one of the most controversial. However, because of its fragmentary record, several issues regarding its phylogenetic emplacement and its ecology remain unsolved or unknown. The discovery of a single specimen attributed to Allodaposuchus, represented by both cranial and postcranial remains, from the Casa Fabà site (Tremp Basin, NE Spain in the lower red unit of the Tremp Fm. (early Maastrichtian, Late Cretaceous offers a unique opportunity to deepen in the phylogenetic relationships of the group and its ecological features.Methods. The specimen is described in detail, and CT scan of the skull is performed in order to study the endocranial morphology as well as paratympanic sinuses configuration. In addition, myological and phylogenetic analyses are also carried out on the specimen for to shed light in ecological and phylogenetic issues, respectively.Results. The specimen described herein represents a new species, Allodaposuchus hulki sp. nov., closely related to the Romanian A. precedens. The CT scan of the skull revealed an unexpected paratympanic sinuses configuration. Allosaposuchus hulki exhibits an “anterodorsal tympanic sinus” not observed in any other extant or extinct crocodilian. The caudal tympanic recesses are extremely enlarged, and the expanded quadratic sinus seems to be connected to the middle-ear channel. Phylogenetic analyses confirm the emplacement of the informal taxonomic group ‘Allodaposuchia’ at the base of Crocodylia, being considered the sister group of Borealosuchus and Planocraniidae.Discussion. Although this is a preliminary hypothesis, the unique paratympanic configuration displayed by A. hulki suggests that it could

Quantitative PCR high-resolution melting (qPCR-HRM) curve analysis, a new approach to simultaneously screen point mutations and large rearrangements: application to MLH1 germline mutations in Lynch syndrome.

Science.gov (United States)

Rouleau, Etienne; Lefol, Cédrick; Bourdon, Violaine; Coulet, Florence; Noguchi, Tetsuro; Soubrier, Florent; Bièche, Ivan; Olschwang, Sylviane; Sobol, Hagay; Lidereau, Rosette

2009-06-01

Several techniques have been developed to screen mismatch repair (MMR) genes for deleterious mutations. Until now, two different techniques were required to screen for both point mutations and large rearrangements. For the first time, we propose a new approach, called "quantitative PCR (qPCR) high-resolution melting (HRM) curve analysis (qPCR-HRM)," which combines qPCR and HRM to obtain a rapid and cost-effective method suitable for testing a large series of samples. We designed PCR amplicons to scan the MLH1 gene using qPCR HRM. Seventy-six patients were fully scanned in replicate, including 14 wild-type patients and 62 patients with known mutations (57 point mutations and five rearrangements). To validate the detected mutations, we used sequencing and/or hybridization on a dedicated MLH1 array-comparative genomic hybridization (array-CGH). All point mutations and rearrangements detected by denaturing high-performance liquid chromatography (dHPLC)+multiplex ligation-dependent probe amplification (MLPA) were successfully detected by qPCR HRM. Three large rearrangements were characterized with the dedicated MLH1 array-CGH. One variant was detected with qPCR HRM in a wild-type patient and was located within the reverse primer. One variant was not detected with qPCR HRM or with dHPLC due to its proximity to a T-stretch. With qPCR HRM, prescreening for point mutations and large rearrangements are performed in one tube and in one step with a single machine, without the need for any automated sequencer in the prescreening process. In replicate, its reagent cost, sensitivity, and specificity are comparable to those of dHPLC+MLPA techniques. However, qPCR HRM outperformed the other techniques in terms of its rapidity and amount of data provided.

Phylogenetic Position of Barbus lacerta Heckel, 1843

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Mustafa Korkmaz

2015-11-01

As a result, five clades come out from phylogenetic reconstruction and in phylogenetic tree Barbus lacerta determined to be sister group of Barbus macedonicus, Barbus oligolepis and Barbus plebejus complex.

The phylogenetics of succession can guide restoration

DEFF Research Database (Denmark)

Shooner, Stephanie; Chisholm, Chelsea Lee; Davies, T. Jonathan

2015-01-01

Phylogenetic tools have increasingly been used in community ecology to describe the evolutionary relationships among co-occurring species. In studies of succession, such tools may allow us to identify the evolutionary lineages most suited for particular stages of succession and habitat...... rehabilitation. However, to date, these two applications have been largely separate. Here, we suggest that information on phylogenetic community structure might help to inform community restoration strategies following major disturbance. Our study examined phylogenetic patterns of succession based...... for species sorting along abiotic gradients (slope and aspect) on the mine sites that had been abandoned for the longest. Synthesis and applications. Understanding the trajectory of succession is critical for restoration efforts. Our results suggest that early colonizers represent a phylogenetically random...

Effects of Phylogenetic Tree Style on Student Comprehension

Science.gov (United States)

Dees, Jonathan Andrew

Phylogenetic trees are powerful tools of evolutionary biology that have become prominent across the life sciences. Consequently, learning to interpret and reason from phylogenetic trees is now an essential component of biology education. However, students often struggle to understand these diagrams, even after explicit instruction. One factor that has been observed to affect student understanding of phylogenetic trees is style (i.e., diagonal or bracket). The goal of this dissertation research was to systematically explore effects of style on student interpretations and construction of phylogenetic trees in the context of an introductory biology course. Before instruction, students were significantly more accurate with bracket phylogenetic trees for a variety of interpretation and construction tasks. Explicit instruction that balanced the use of diagonal and bracket phylogenetic trees mitigated some, but not all, style effects. After instruction, students were significantly more accurate for interpretation tasks involving taxa relatedness and construction exercises when using the bracket style. Based on this dissertation research and prior studies on style effects, I advocate for introductory biology instructors to use only the bracket style. Future research should examine causes of style effects and variables other than style to inform the development of research-based instruction that best supports student understanding of phylogenetic trees.

A mutational analysis of Caenorhabditis elegans in space

Energy Technology Data Exchange (ETDEWEB)

Zhao Yang [Department of Medical Genetics, University of British Columbia, Life Sciences Centre, Room 1364-2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3 (Canada); Lai, Kenneth [Department of Medical Genetics, University of British Columbia, Life Sciences Centre, Room 1364-2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3 (Canada); Cheung, Iris [Department of Medical Genetics, University of British Columbia, Life Sciences Centre, Room 1364-2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3 (Canada); Youds, Jillian [Department of Medical Genetics, University of British Columbia, Life Sciences Centre, Room 1364-2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3 (Canada); Tarailo, Maja [Department of Medical Genetics, University of British Columbia, Life Sciences Centre, Room 1364-2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3 (Canada); Tarailo, Sanja [Department of Medical Genetics, University of British Columbia, Life Sciences Centre, Room 1364-2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3 (Canada); Rose, Ann [Department of Medical Genetics, University of British Columbia, Life Sciences Centre, Room 1364-2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3 (Canada)]. E-mail: arose@gene.nce.ubc.ca

2006-10-10

The International Caenorhabditis elegans Experiment First Flight (ICE-First) was a project using C. elegans as a model organism to study the biological effects of short duration spaceflight (11 days in the International Space Station). As a member of the ICE-First research team, our group focused on the mutational effects of spaceflight. Several approaches were taken to measure mutational changes that occurred during the spaceflight including measurement of the integrity of poly-G/poly-C tracts, determination of the mutation frequency in the unc-22 gene, analysis of lethal mutations captured by the genetic balancer eT1(III;V), and identification of alterations in telomere length. By comparing the efficiency, sensitivity, and convenience of these methods, we deduced that the eT1 balancer system is well-suited for capturing, maintaining and recovering mutational events that occur over several generations during spaceflight. In the course of this experiment, we have extended the usefulness of the eT1 balancer system by identifying the physical breakpoints of the eT1 translocation and have developed a PCR assay to follow the eT1 chromosomes. C. elegans animals were grown in a defined liquid media during the spaceflight. This is the first analysis of genetic changes in C. elegans grown in the defined media. Although no significant difference in mutation rate was detected between spaceflight and control samples, which is not surprising given the short duration of the spaceflight, we demonstrate here the utility of worms as an integrating biological dosimeter for spaceflight.

A mutational analysis of Caenorhabditis elegans in space

International Nuclear Information System (INIS)

Zhao Yang; Lai, Kenneth; Cheung, Iris; Youds, Jillian; Tarailo, Maja; Tarailo, Sanja; Rose, Ann

2006-01-01

The International Caenorhabditis elegans Experiment First Flight (ICE-First) was a project using C. elegans as a model organism to study the biological effects of short duration spaceflight (11 days in the International Space Station). As a member of the ICE-First research team, our group focused on the mutational effects of spaceflight. Several approaches were taken to measure mutational changes that occurred during the spaceflight including measurement of the integrity of poly-G/poly-C tracts, determination of the mutation frequency in the unc-22 gene, analysis of lethal mutations captured by the genetic balancer eT1(III;V), and identification of alterations in telomere length. By comparing the efficiency, sensitivity, and convenience of these methods, we deduced that the eT1 balancer system is well-suited for capturing, maintaining and recovering mutational events that occur over several generations during spaceflight. In the course of this experiment, we have extended the usefulness of the eT1 balancer system by identifying the physical breakpoints of the eT1 translocation and have developed a PCR assay to follow the eT1 chromosomes. C. elegans animals were grown in a defined liquid media during the spaceflight. This is the first analysis of genetic changes in C. elegans grown in the defined media. Although no significant difference in mutation rate was detected between spaceflight and control samples, which is not surprising given the short duration of the spaceflight, we demonstrate here the utility of worms as an integrating biological dosimeter for spaceflight

Robust identification of noncoding RNA from transcriptomes requires phylogenetically-informed sampling.

Directory of Open Access Journals (Sweden)

Stinus Lindgreen

2014-10-01

Full Text Available Noncoding RNAs are integral to a wide range of biological processes, including translation, gene regulation, host-pathogen interactions and environmental sensing. While genomics is now a mature field, our capacity to identify noncoding RNA elements in bacterial and archaeal genomes is hampered by the difficulty of de novo identification. The emergence of new technologies for characterizing transcriptome outputs, notably RNA-seq, are improving noncoding RNA identification and expression quantification. However, a major challenge is to robustly distinguish functional outputs from transcriptional noise. To establish whether annotation of existing transcriptome data has effectively captured all functional outputs, we analysed over 400 publicly available RNA-seq datasets spanning 37 different Archaea and Bacteria. Using comparative tools, we identify close to a thousand highly-expressed candidate noncoding RNAs. However, our analyses reveal that capacity to identify noncoding RNA outputs is strongly dependent on phylogenetic sampling. Surprisingly, and in stark contrast to protein-coding genes, the phylogenetic window for effective use of comparative methods is perversely narrow: aggregating public datasets only produced one phylogenetic cluster where these tools could be used to robustly separate unannotated noncoding RNAs from a null hypothesis of transcriptional noise. Our results show that for the full potential of transcriptomics data to be realized, a change in experimental design is paramount: effective transcriptomics requires phylogeny-aware sampling.

Phylogenetic Structure of Plant Communities: Are Polyploids Distantly Related to Co-occurring Diploids?

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Michelle L. Gaynor

2018-04-01

Full Text Available Polyploidy is widely acknowledged to have played an important role in the evolution and diversification of vascular plants. However, the influence of genome duplication on population-level dynamics and its cascading effects at the community level remain unclear. In part, this is due to persistent uncertainties over the extent of polyploid phenotypic variation, and the interactions between polyploids and co-occurring species, and highlights the need to integrate polyploid research at the population and community level. Here, we investigate how community-level patterns of phylogenetic relatedness might influence escape from minority cytotype exclusion, a classic population genetics hypothesis about polyploid establishment, and population-level species interactions. Focusing on two plant families in which polyploidy has evolved multiple times, Brassicaceae and Rosaceae, we build upon the hypothesis that the greater allelic and phenotypic diversity of polyploids allow them to successfully inhabit a different geographic range compared to their diploid progenitor and close relatives. Using a phylogenetic framework, we specifically test (1 whether polyploid species are more distantly related to diploids within the same community than co-occurring diploids are to one another, and (2 if polyploid species tend to exhibit greater ecological success than diploids, using species abundance in communities as an indicator of successful establishment. Overall, our results suggest that the effects of genome duplication on community structure are not clear-cut. We find that polyploid species tend to be more distantly related to co-occurring diploids than diploids are to each other. However, we do not find a consistent pattern of polyploid species being more abundant than diploid species, suggesting polyploids are not uniformly more ecologically successful than diploids. While polyploidy appears to have some important influences on species co-occurrence in

Nucleotide diversity and phylogenetic relationships among ...

Indian Academy of Sciences (India)

Navya

2 attached at the base of tree as the diverging Iridaceae relative's lineage. Present study revealed that psbA-trnH region are useful in addressing questions of phylogenetic relationships among the Gladiolus cultivars, as these intergenic spacers are more variable and have more phylogenetically informative sites than the ...

Point estimates in phylogenetic reconstructions

OpenAIRE

Benner, Philipp; Bacak, Miroslav; Bourguignon, Pierre-Yves

2013-01-01

Motivation: The construction of statistics for summarizing posterior samples returned by a Bayesian phylogenetic study has so far been hindered by the poor geometric insights available into the space of phylogenetic trees, and ad hoc methods such as the derivation of a consensus tree makeup for the ill-definition of the usual concepts of posterior mean, while bootstrap methods mitigate the absence of a sound concept of variance. Yielding satisfactory results with sufficiently concentrated pos...

Protein Homeostasis Imposes a Barrier on Functional Integration of Horizontally Transferred Genes in Bacteria.

Science.gov (United States)

Bershtein, Shimon; Serohijos, Adrian W R; Bhattacharyya, Sanchari; Manhart, Michael; Choi, Jeong-Mo; Mu, Wanmeng; Zhou, Jingwen; Shakhnovich, Eugene I

2015-10-01

Horizontal gene transfer (HGT) plays a central role in bacterial evolution, yet the molecular and cellular constraints on functional integration of the foreign genes are poorly understood. Here we performed inter-species replacement of the chromosomal folA gene, encoding an essential metabolic enzyme dihydrofolate reductase (DHFR), with orthologs from 35 other mesophilic bacteria. The orthologous inter-species replacements caused a marked drop (in the range 10-90%) in bacterial growth rate despite the fact that most orthologous DHFRs are as stable as E.coli DHFR at 37°C and are more catalytically active than E. coli DHFR. Although phylogenetic distance between E. coli and orthologous DHFRs as well as their individual molecular properties correlate poorly with growth rates, the product of the intracellular DHFR abundance and catalytic activity (kcat/KM), correlates strongly with growth rates, indicating that the drop in DHFR abundance constitutes the major fitness barrier to HGT. Serial propagation of the orthologous strains for ~600 generations dramatically improved growth rates by largely alleviating the fitness barriers. Whole genome sequencing and global proteome quantification revealed that the evolved strains with the largest fitness improvements have accumulated mutations that inactivated the ATP-dependent Lon protease, causing an increase in the intracellular DHFR abundance. In one case DHFR abundance increased further due to mutations accumulated in folA promoter, but only after the lon inactivating mutations were fixed in the population. Thus, by apparently distinguishing between self and non-self proteins, protein homeostasis imposes an immediate and global barrier to the functional integration of foreign genes by decreasing the intracellular abundance of their products. Once this barrier is alleviated, more fine-tuned evolution occurs to adjust the function/expression of the transferred proteins to the constraints imposed by the intracellular

Protein Homeostasis Imposes a Barrier on Functional Integration of Horizontally Transferred Genes in Bacteria.

Directory of Open Access Journals (Sweden)

Shimon Bershtein

2015-10-01

Full Text Available Horizontal gene transfer (HGT plays a central role in bacterial evolution, yet the molecular and cellular constraints on functional integration of the foreign genes are poorly understood. Here we performed inter-species replacement of the chromosomal folA gene, encoding an essential metabolic enzyme dihydrofolate reductase (DHFR, with orthologs from 35 other mesophilic bacteria. The orthologous inter-species replacements caused a marked drop (in the range 10-90% in bacterial growth rate despite the fact that most orthologous DHFRs are as stable as E.coli DHFR at 37°C and are more catalytically active than E. coli DHFR. Although phylogenetic distance between E. coli and orthologous DHFRs as well as their individual molecular properties correlate poorly with growth rates, the product of the intracellular DHFR abundance and catalytic activity (kcat/KM, correlates strongly with growth rates, indicating that the drop in DHFR abundance constitutes the major fitness barrier to HGT. Serial propagation of the orthologous strains for ~600 generations dramatically improved growth rates by largely alleviating the fitness barriers. Whole genome sequencing and global proteome quantification revealed that the evolved strains with the largest fitness improvements have accumulated mutations that inactivated the ATP-dependent Lon protease, causing an increase in the intracellular DHFR abundance. In one case DHFR abundance increased further due to mutations accumulated in folA promoter, but only after the lon inactivating mutations were fixed in the population. Thus, by apparently distinguishing between self and non-self proteins, protein homeostasis imposes an immediate and global barrier to the functional integration of foreign genes by decreasing the intracellular abundance of their products. Once this barrier is alleviated, more fine-tuned evolution occurs to adjust the function/expression of the transferred proteins to the constraints imposed by the

Combined amplification and hybridization techniques for genome scanning in vegetatively propagated crops

International Nuclear Information System (INIS)

Kahl, G.; Ramser, J.; Terauchi, R.; Lopez-Peralta, C.; Asemota, H.N.; Weising, K.

1998-01-01

A combination of PCR- and hybridization-based genome scanning techniques and sequence comparisons between non-coding chloroplast DNA flanking tRNA genes has been employed to screen Dioscorea species for intra- and interspecific genetic diversity. This methodology detected extensive polymorphisms within Dioscorea bulbifera L., and revealed taxonomic and phylogenetic relationships among cultivated Guinea yams varieties and their potential wild progenitors. Finally, screening of yam germplasm grown in Jamaica permitted reliable discrimination between all major cultivars. Genome scanning by micro satellite-primed PCR (MP-PCR) and random amplified polymorphic DNA (RAPD) analysis in combination with the novel random amplified micro satellite polymorphisms (RAMPO) hybridization technique has shown high potential for the genetic analysis of yams, and holds promise for other vegetatively propagated orphan crops. (author)

Sharing and re-use of phylogenetic trees (and associated data) to facilitate synthesis.

Science.gov (United States)

Stoltzfus, Arlin; O'Meara, Brian; Whitacre, Jamie; Mounce, Ross; Gillespie, Emily L; Kumar, Sudhir; Rosauer, Dan F; Vos, Rutger A

2012-10-22

Recently, various evolution-related journals adopted policies to encourage or require archiving of phylogenetic trees and associated data. Such attention to practices that promote sharing of data reflects rapidly improving information technology, and rapidly expanding potential to use this technology to aggregate and link data from previously published research. Nevertheless, little is known about current practices, or best practices, for publishing trees and associated data so as to promote re-use. Here we summarize results of an ongoing analysis of current practices for archiving phylogenetic trees and associated data, current practices of re-use, and current barriers to re-use. We find that the technical infrastructure is available to support rudimentary archiving, but the frequency of archiving is low. Currently, most phylogenetic knowledge is not easily re-used due to a lack of archiving, lack of awareness of best practices, and lack of community-wide standards for formatting data, naming entities, and annotating data. Most attempts at data re-use seem to end in disappointment. Nevertheless, we find many positive examples of data re-use, particularly those that involve customized species trees generated by grafting to, and pruning from, a much larger tree. The technologies and practices that facilitate data re-use can catalyze synthetic and integrative research. However, success will require engagement from various stakeholders including individual scientists who produce or consume shareable data, publishers, policy-makers, technology developers and resource-providers. The critical challenges for facilitating re-use of phylogenetic trees and associated data, we suggest, include: a broader commitment to public archiving; more extensive use of globally meaningful identifiers; development of user-friendly technology for annotating, submitting, searching, and retrieving data and their metadata; and development of a minimum reporting standard (MIAPA) indicating

Linking IMAGE 2 and WORLD SCAN

International Nuclear Information System (INIS)

Gelauff, G.; Geurts, B.; Gielen, A.; Den Ouden, A.; Alcamo, J.; Gerlagh, R.

1995-01-01

The links between the climate model IMAGE 2 and the economic model WORLD SCAN, which are set up to obtain an integrated scenario instrument for comprehensive and consistent climate-economy scenarios, are presented and discussed. The links are made with respect to energy (in WORLD SCAN) and agriculture (in IMAGE 2), thus providing a consistent linkage with feedbacks running both ways. 2 figs., 1 tab

Analysis of 30 putative BRCA1 splicing mutations in hereditary breast and ovarian cancer families identifies exonic splice site mutations that escape in silico prediction.

Directory of Open Access Journals (Sweden)

Barbara Wappenschmidt

Full Text Available Screening for pathogenic mutations in breast and ovarian cancer genes such as BRCA1/2, CHEK2 and RAD51C is common practice for individuals from high-risk families. However, test results may be ambiguous due to the presence of unclassified variants (UCV in the concurrent absence of clearly cancer-predisposing mutations. Especially the presence of intronic or exonic variants within these genes that possibly affect proper pre-mRNA processing poses a challenge as their functional implications are not immediately apparent. Therefore, it appears necessary to characterize potential splicing UCV and to develop appropriate classification tools. We investigated 30 distinct BRCA1 variants, both intronic and exonic, regarding their spliceogenic potential by commonly used in silico prediction algorithms (HSF, MaxEntScan along with in vitro transcript analyses. A total of 25 variants were identified spliceogenic, either causing/enhancing exon skipping or activation of cryptic splice sites, or both. Except from a single intronic variant causing minor effects on BRCA1 pre-mRNA processing in our analyses, 23 out of 24 intronic variants were correctly predicted by MaxEntScan, while HSF was less accurate in this cohort. Among the 6 exonic variants analyzed, 4 severely impair correct pre-mRNA processing, while the remaining two have partial effects. In contrast to the intronic alterations investigated, only half of the spliceogenic exonic variants were correctly predicted by HSF and/or MaxEntScan. These data support the idea that exonic splicing mutations are commonly disease-causing and concurrently prone to escape in silico prediction, hence necessitating experimental in vitro splicing analysis.

Characterization of Escherichia coli Phylogenetic Groups ...

African Journals Online (AJOL)

Background: Escherichia coli strains mainly fall into four phylogenetic groups (A, B1, B2, and D) and that virulent extra‑intestinal strains mainly belong to groups B2 and D. Aim: The aim was to determine the association between phylogenetic groups of E. coli causing extraintestinal infections (ExPEC) regarding the site of ...

CAMAC gamma ray scanning system

International Nuclear Information System (INIS)

Moss, C.E.; Pratt, J.C.; Shunk, E.R.

1981-01-01

A flexible gamma-ray scanning system, based on a LeCroy 3500 multichannel analyzer and CAMAC modules, is described. The system is designed for making simultaneous passive and active scans of objects of interest to nuclear safeguards. The scanner is a stepping-motor-driven carriage; the detectors, a bismuth-germanate scintillator and a high-purity germanium detector. A total of sixteen peaks in the two detector-produced spectra can be integrated simultaneously, and any scan can be viewed during data acquisition. For active scanning, the 2615-keV gamma-ray line from a 232 U source and the 4439-keV gamma-ray line from 9 Be(α,n) 12 C were selected. The system can be easily reconfigured to accommodate up to seven detectors because it is based on CAMAC modules and FORTRAN. The system is designed for field use and is easily transported. Examples of passive and active scans are presented

Experimental Determination and Prediction of the Fitness Effects of Random Point Mutations in the Biosynthetic Enzyme HisA

Science.gov (United States)

Lundin, Erik; Tang, Po-Cheng; Guy, Lionel; Näsvall, Joakim; Andersson, Dan I

2018-01-01

Abstract The distribution of fitness effects of mutations is a factor of fundamental importance in evolutionary biology. We determined the distribution of fitness effects of 510 mutants that each carried between 1 and 10 mutations (synonymous and nonsynonymous) in the hisA gene, encoding an essential enzyme in the l-histidine biosynthesis pathway of Salmonella enterica. For the full set of mutants, the distribution was bimodal with many apparently neutral mutations and many lethal mutations. For a subset of 81 single, nonsynonymous mutants most mutations appeared neutral at high expression levels, whereas at low expression levels only a few mutations were neutral. Furthermore, we examined how the magnitude of the observed fitness effects was correlated to several measures of biophysical properties and phylogenetic conservation.We conclude that for HisA: (i) The effect of mutations can be masked by high expression levels, such that mutations that are deleterious to the function of the protein can still be neutral with regard to organism fitness if the protein is expressed at a sufficiently high level; (ii) the shape of the fitness distribution is dependent on the extent to which the protein is rate-limiting for growth; (iii) negative epistatic interactions, on an average, amplified the combined effect of nonsynonymous mutations; and (iv) no single sequence-based predictor could confidently predict the fitness effects of mutations in HisA, but a combination of multiple predictors could predict the effect with a SD of 0.04 resulting in 80% of the mutations predicted within 12% of their observed selection coefficients. PMID:29294020

Muscle imaging in patients with tubular aggregate myopathy caused by mutations in STIM1

DEFF Research Database (Denmark)

Tasca, Giorgio; D'Amico, Adele; Monforte, Mauro

2015-01-01

Tubular aggregate myopathy is a genetically heterogeneous disease characterized by tubular aggregates as the hallmark on muscle biopsy. Mutations in STIM1 have recently been identified as one genetic cause in a number of tubular aggregate myopathy cases. To characterize the pattern of muscle...... involvement in this disease, upper and lower girdles and lower limbs were imaged in five patients with mutations in STIM1, and the scans were compared with two patients with tubular aggregate myopathy not caused by mutations in STIM1. A common pattern of involvement was found in STIM1-mutated patients...... of thigh and posterior leg with sparing of gracilis, tibialis anterior and, to a lesser extent, short head of biceps femoris. Mutations in STIM1 are associated with a homogeneous involvement on imaging despite variable clinical features. Muscle imaging can be useful in identifying STIM1-mutated patients...

Visualizing phylogenetic tree landscapes.

Science.gov (United States)

Wilgenbusch, James C; Huang, Wen; Gallivan, Kyle A

2017-02-02

Genomic-scale sequence alignments are increasingly used to infer phylogenies in order to better understand the processes and patterns of evolution. Different partitions within these new alignments (e.g., genes, codon positions, and structural features) often favor hundreds if not thousands of competing phylogenies. Summarizing and comparing phylogenies obtained from multi-source data sets using current consensus tree methods discards valuable information and can disguise potential methodological problems. Discovery of efficient and accurate dimensionality reduction methods used to display at once in 2- or 3- dimensions the relationship among these competing phylogenies will help practitioners diagnose the limits of current evolutionary models and potential problems with phylogenetic reconstruction methods when analyzing large multi-source data sets. We introduce several dimensionality reduction methods to visualize in 2- and 3-dimensions the relationship among competing phylogenies obtained from gene partitions found in three mid- to large-size mitochondrial genome alignments. We test the performance of these dimensionality reduction methods by applying several goodness-of-fit measures. The intrinsic dimensionality of each data set is also estimated to determine whether projections in 2- and 3-dimensions can be expected to reveal meaningful relationships among trees from different data partitions. Several new approaches to aid in the comparison of different phylogenetic landscapes are presented. Curvilinear Components Analysis (CCA) and a stochastic gradient decent (SGD) optimization method give the best representation of the original tree-to-tree distance matrix for each of the three- mitochondrial genome alignments and greatly outperformed the method currently used to visualize tree landscapes. The CCA + SGD method converged at least as fast as previously applied methods for visualizing tree landscapes. We demonstrate for all three mtDNA alignments that 3D

Biomass pyrolysis and combustion integral and differential reaction heats with temperatures using thermogravimetric analysis/differential scanning calorimetry.

Science.gov (United States)

Shen, Jiacheng; Igathinathane, C; Yu, Manlu; Pothula, Anand Kumar

2015-06-01

Integral reaction heats of switchgrass, big bluestem, and corn stalks were determined using thermogravimetric analysis/differential scanning calorimetry (TGA/DSC). Iso-conversion differential reaction heats using TGA/DSC pyrolysis and combustion of biomass were not available, despite reports available on heats required and released. A concept of iso-conversion differential reaction heats was used to determine the differential reaction heats of each thermal characteristics segment of these materials. Results showed that the integral reaction heats were endothermic from 30 to 700°C for pyrolysis of switchgrass and big bluestem, but they were exothermic for corn stalks prior to 587°C. However, the integral reaction heats for combustion of the materials followed an endothermic to exothermic transition. The differential reaction heats of switchgrass pyrolysis were predominantly endothermic in the fraction of mass loss (0.0536-0.975), and were exothermic for corn stalks (0.0885-0.850) and big bluestem (0.736-0.919). Study results provided better insight into biomass thermal mechanism. Published by Elsevier Ltd.

Large-Scale Genomic Analysis of Codon Usage in Dengue Virus and Evaluation of Its Phylogenetic Dependence

Directory of Open Access Journals (Sweden)

Edgar E. Lara-Ramírez

2014-01-01

Full Text Available The increasing number of dengue virus (DENV genome sequences available allows identifying the contributing factors to DENV evolution. In the present study, the codon usage in serotypes 1–4 (DENV1–4 has been explored for 3047 sequenced genomes using different statistics methods. The correlation analysis of total GC content (GC with GC content at the three nucleotide positions of codons (GC1, GC2, and GC3 as well as the effective number of codons (ENC, ENCp versus GC3 plots revealed mutational bias and purifying selection pressures as the major forces influencing the codon usage, but with distinct pressure on specific nucleotide position in the codon. The correspondence analysis (CA and clustering analysis on relative synonymous codon usage (RSCU within each serotype showed similar clustering patterns to the phylogenetic analysis of nucleotide sequences for DENV1–4. These clustering patterns are strongly related to the virus geographic origin. The phylogenetic dependence analysis also suggests that stabilizing selection acts on the codon usage bias. Our analysis of a large scale reveals new feature on DENV genomic evolution.

Environmental and spatial drivers of taxonomic, functional, and phylogenetic characteristics of bat communities in human-modified landscapes

Science.gov (United States)

Fagan, Matthew E.; Willig, Michael R.

2016-01-01

Background Assembly of species into communities following human disturbance (e.g., deforestation, fragmentation) may be governed by spatial (e.g., dispersal) or environmental (e.g., niche partitioning) mechanisms. Variation partitioning has been used to broadly disentangle spatial and environmental mechanisms, and approaches utilizing functional and phylogenetic characteristics of communities have been implemented to determine the relative importance of particular environmental (or niche-based) mechanisms. Nonetheless, few studies have integrated these quantitative approaches to comprehensively assess the relative importance of particular structuring processes. Methods We employed a novel variation partitioning approach to evaluate the relative importance of particular spatial and environmental drivers of taxonomic, functional, and phylogenetic aspects of bat communities in a human-modified landscape in Costa Rica. Specifically, we estimated the amount of variation in species composition (taxonomic structure) and in two aspects of functional and phylogenetic structure (i.e., composition and dispersion) along a forest loss and fragmentation gradient that are uniquely explained by landscape characteristics (i.e., environment) or space to assess the importance of competing mechanisms. Results The unique effects of space on taxonomic, functional and phylogenetic structure were consistently small. In contrast, landscape characteristics (i.e., environment) played an appreciable role in structuring bat communities. Spatially-structured landscape characteristics explained 84% of the variation in functional or phylogenetic dispersion, and the unique effects of landscape characteristics significantly explained 14% of the variation in species composition. Furthermore, variation in bat community structure was primarily due to differences in dispersion of species within functional or phylogenetic space along the gradient, rather than due to differences in functional or

Environmental and spatial drivers of taxonomic, functional, and phylogenetic characteristics of bat communities in human-modified landscapes.

Science.gov (United States)

Cisneros, Laura M; Fagan, Matthew E; Willig, Michael R

2016-01-01

Assembly of species into communities following human disturbance (e.g., deforestation, fragmentation) may be governed by spatial (e.g., dispersal) or environmental (e.g., niche partitioning) mechanisms. Variation partitioning has been used to broadly disentangle spatial and environmental mechanisms, and approaches utilizing functional and phylogenetic characteristics of communities have been implemented to determine the relative importance of particular environmental (or niche-based) mechanisms. Nonetheless, few studies have integrated these quantitative approaches to comprehensively assess the relative importance of particular structuring processes. We employed a novel variation partitioning approach to evaluate the relative importance of particular spatial and environmental drivers of taxonomic, functional, and phylogenetic aspects of bat communities in a human-modified landscape in Costa Rica. Specifically, we estimated the amount of variation in species composition (taxonomic structure) and in two aspects of functional and phylogenetic structure (i.e., composition and dispersion) along a forest loss and fragmentation gradient that are uniquely explained by landscape characteristics (i.e., environment) or space to assess the importance of competing mechanisms. The unique effects of space on taxonomic, functional and phylogenetic structure were consistently small. In contrast, landscape characteristics (i.e., environment) played an appreciable role in structuring bat communities. Spatially-structured landscape characteristics explained 84% of the variation in functional or phylogenetic dispersion, and the unique effects of landscape characteristics significantly explained 14% of the variation in species composition. Furthermore, variation in bat community structure was primarily due to differences in dispersion of species within functional or phylogenetic space along the gradient, rather than due to differences in functional or phylogenetic composition. Variation

A Practical Algorithm for Reconstructing Level-1 Phylogenetic Networks

NARCIS (Netherlands)

K.T. Huber; L.J.J. van Iersel (Leo); S.M. Kelk (Steven); R. Suchecki

2010-01-01

htmlabstractRecently much attention has been devoted to the construction of phylogenetic networks which generalize phylogenetic trees in order to accommodate complex evolutionary processes. Here we present an efficient, practical algorithm for reconstructing level-1 phylogenetic networks - a type of

A practical algorithm for reconstructing level-1 phylogenetic networks

NARCIS (Netherlands)

Huber, K.T.; Iersel, van L.J.J.; Kelk, S.M.; Suchecki, R.

2011-01-01

Recently, much attention has been devoted to the construction of phylogenetic networks which generalize phylogenetic trees in order to accommodate complex evolutionary processes. Here, we present an efficient, practical algorithm for reconstructing level-1 phylogenetic networks-a type of network

Phylogenetic analysis of emergent Streptococcus pneumoniae serotype 22F causing invasive pneumococcal disease using whole genome sequencing.

Directory of Open Access Journals (Sweden)

Walter H B Demczuk

Full Text Available Since implementation of the 13-valent polyvalent conjugate vaccine (PCV13 in Canada during 2010, the proportion of PCV13 serotypes causing invasive pneumococcal disease (IPD has declined from 55% (n = 1492 in 2010 to 31% (n = 764 in 2014. A concurrent increase of non-PCV13 serotypes has occurred and 22F has become the most prevalent serotype in Canada increasing from 7% (n = 183 to 11% (n = 283. Core single nucleotide variant phylogenetic analysis was performed on 137 Streptococcus pneumoniae serotype 22F isolates collected across Canada from 2005-2015. Six phylogenetic lineages (n = 117 were identified among a serotype 22F/ST433 clonal complex (CC, including a recently expanding erythromycin-resistant clone. Erythromycin-resistance was observed in 25 isolates possessing ermB, mef or a 23S rRNA A2061G point mutation; 2 penicillin-resistant isolates had recombinant pbp1a, pbp2a and/or pbp2x; 3 tetracycline-resistant isolates contained tetM; and 1 isolate was multidrug-resistant. Virulence factor analysis indicated a high level of homogeneity among the 22F/ST433 clonal complex strains. A group of 6 phylogenetic outlier strains had differing MLST, antimicrobial resistance and molecular profiles suggestive of capsule switching events. While capsule switch events among S. pneumoniae serotype 22F has been observed, increasing prevalence of S. pneumoniae serotype 22F can be attributed to an evolving homogenous clone expanding nationally through local transmission events.

Folding and unfolding phylogenetic trees and networks.

Science.gov (United States)

Huber, Katharina T; Moulton, Vincent; Steel, Mike; Wu, Taoyang

2016-12-01

Phylogenetic networks are rooted, labelled directed acyclic graphswhich are commonly used to represent reticulate evolution. There is a close relationship between phylogenetic networks and multi-labelled trees (MUL-trees). Indeed, any phylogenetic network N can be "unfolded" to obtain a MUL-tree U(N) and, conversely, a MUL-tree T can in certain circumstances be "folded" to obtain aphylogenetic network F(T) that exhibits T. In this paper, we study properties of the operations U and F in more detail. In particular, we introduce the class of stable networks, phylogenetic networks N for which F(U(N)) is isomorphic to N, characterise such networks, and show that they are related to the well-known class of tree-sibling networks. We also explore how the concept of displaying a tree in a network N can be related to displaying the tree in the MUL-tree U(N). To do this, we develop aphylogenetic analogue of graph fibrations. This allows us to view U(N) as the analogue of the universal cover of a digraph, and to establish a close connection between displaying trees in U(N) and reconciling phylogenetic trees with networks.

Topological variation in single-gene phylogenetic trees

OpenAIRE

Castresana, Jose

2007-01-01

A recent large-scale phylogenomic study has shown the great degree of topological variation that can be found among eukaryotic phylogenetic trees constructed from single genes, highlighting the problems that can be associated with gene sampling in phylogenetic studies.

Transverse section radionuclide scanning system

International Nuclear Information System (INIS)

Kuhl, D.E.; Edwards, R.Q.

1976-01-01

This invention provides a transverse section radionuclide scanning system for high-sensitivity quantification of brain radioactivity in cross-section picture format in order to permit accurate assessment of regional brain function localized in three dimensions. High sensitivity crucially depends on overcoming the heretofore known raster type scanning, which requires back and forth detector movement involving dead-time or partial enclosure of the scan field. Accordingly, this invention provides a detector array having no back and forth movement by interlaced detectors that enclose the scan field and rotate as an integral unit around one axis of rotation in a slip ring that continuously transmits the detector data by means of laser emitting diodes, with the advantages that increased amounts of data can be continuously collected, processed and displayed with increased sensitivity according to a suitable computer program. 5 claims, 11 figures

Dynamic autofocus for continuous-scanning time-delay-and-integration image acquisition in automated microscopy.

Science.gov (United States)

Bravo-Zanoguera, Miguel E; Laris, Casey A; Nguyen, Lam K; Oliva, Mike; Price, Jeffrey H

2007-01-01

Efficient image cytometry of a conventional microscope slide means rapid acquisition and analysis of 20 gigapixels of image data (at 0.3-microm sampling). The voluminous data motivate increased acquisition speed to enable many biomedical applications. Continuous-motion time-delay-and-integrate (TDI) scanning has the potential to speed image acquisition while retaining sensitivity, but the challenge of implementing high-resolution autofocus operating simultaneously with acquisition has limited its adoption. We develop a dynamic autofocus system for this need using: 1. a "volume camera," consisting of nine fiber optic imaging conduits to charge-coupled device (CCD) sensors, that acquires images in parallel from different focal planes, 2. an array of mixed analog-digital processing circuits that measure the high spatial frequencies of the multiple image streams to create focus indices, and 3. a software system that reads and analyzes the focus data streams and calculates best focus for closed feedback loop control. Our system updates autofocus at 56 Hz (or once every 21 microm of stage travel) to collect sharply focused images sampled at 0.3x0.3 microm(2)/pixel at a stage speed of 2.3 mms. The system, tested by focusing in phase contrast and imaging long fluorescence strips, achieves high-performance closed-loop image-content-based autofocus in continuous scanning for the first time.

Sequence comparison and phylogenetic analysis of core gene of ...

African Journals Online (AJOL)

Phylogenetic analysis suggests that our sequences are clustered with sequences reported from Japan. This is the first phylogenetic analysis of HCV core gene from Pakistani population. Our sequences and sequences from Japan are grouped into same cluster in the phylogenetic tree. Sequence comparison and ...

PhyDesign: an online application for profiling phylogenetic informativeness

Directory of Open Access Journals (Sweden)

Townsend Jeffrey P

2011-05-01

Full Text Available Abstract Background The rapid increase in number of sequenced genomes for species across of the tree of life is revealing a diverse suite of orthologous genes that could potentially be employed to inform molecular phylogenetic studies that encompass broader taxonomic sampling. Optimal usage of this diversity of loci requires user-friendly tools to facilitate widespread cost-effective locus prioritization for phylogenetic sampling. The Townsend (2007 phylogenetic informativeness provides a unique empirical metric for guiding marker selection. However, no software or automated methodology to evaluate sequence alignments and estimate the phylogenetic informativeness metric has been available. Results Here, we present PhyDesign, a platform-independent online application that implements the Townsend (2007 phylogenetic informativeness analysis, providing a quantitative prediction of the utility of loci to solve specific phylogenetic questions. An easy-to-use interface facilitates uploading of alignments and ultrametric trees to calculate and depict profiles of informativeness over specified time ranges, and provides rankings of locus prioritization for epochs of interest. Conclusions By providing these profiles, PhyDesign facilitates locus prioritization increasing the efficiency of sequencing for phylogenetic purposes compared to traditional studies with more laborious and low capacity screening methods, as well as increasing the accuracy of phylogenetic studies. Together with a manual and sample files, the application is freely accessible at http://phydesign.townsend.yale.edu.

An optical scanning subsystem for a UAS-enabled hyperspectral radiometer

Data.gov (United States)

National Aeronautics and Space Administration — Hyperspectral radiometers will be integrated with an optical scanning subsystem to measure remote sensing reflectance spectra over the ocean.  The entire scanning...

A phylogenetic blueprint for a modern whale.

Science.gov (United States)

Gatesy, John; Geisler, Jonathan H; Chang, Joseph; Buell, Carl; Berta, Annalisa; Meredith, Robert W; Springer, Mark S; McGowen, Michael R

2013-02-01

The emergence of Cetacea in the Paleogene represents one of the most profound macroevolutionary transitions within Mammalia. The move from a terrestrial habitat to a committed aquatic lifestyle engendered wholesale changes in anatomy, physiology, and behavior. The results of this remarkable transformation are extant whales that include the largest, biggest brained, fastest swimming, loudest, deepest diving mammals, some of which can detect prey with a sophisticated echolocation system (Odontoceti - toothed whales), and others that batch feed using racks of baleen (Mysticeti - baleen whales). A broad-scale reconstruction of the evolutionary remodeling that culminated in extant cetaceans has not yet been based on integration of genomic and paleontological information. Here, we first place Cetacea relative to extant mammalian diversity, and assess the distribution of support among molecular datasets for relationships within Artiodactyla (even-toed ungulates, including Cetacea). We then merge trees derived from three large concatenations of molecular and fossil data to yield a composite hypothesis that encompasses many critical events in the evolutionary history of Cetacea. By combining diverse evidence, we infer a phylogenetic blueprint that outlines the stepwise evolutionary development of modern whales. This hypothesis represents a starting point for more detailed, comprehensive phylogenetic reconstructions in the future, and also highlights the synergistic interaction between modern (genomic) and traditional (morphological+paleontological) approaches that ultimately must be exploited to provide a rich understanding of evolutionary history across the entire tree of Life. Copyright © 2012 Elsevier Inc. All rights reserved.

Phylogenetic Structure of Foliar Spectral Traits in Tropical Forest Canopies

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Kelly M. McManus

2016-02-01

Full Text Available The Spectranomics approach to tropical forest remote sensing has established a link between foliar reflectance spectra and the phylogenetic composition of tropical canopy tree communities vis-à-vis the taxonomic organization of biochemical trait variation. However, a direct relationship between phylogenetic affiliation and foliar reflectance spectra of species has not been established. We sought to develop this relationship by quantifying the extent to which underlying patterns of phylogenetic structure drive interspecific variation among foliar reflectance spectra within three Neotropical canopy tree communities with varying levels of soil fertility. We interpreted the resulting spectral patterns of phylogenetic signal in the context of foliar biochemical traits that may contribute to the spectral-phylogenetic link. We utilized a multi-model ensemble to elucidate trait-spectral relationships, and quantified phylogenetic signal for spectral wavelengths and traits using Pagel’s lambda statistic. Foliar reflectance spectra showed evidence of phylogenetic influence primarily within the visible and shortwave infrared spectral regions. These regions were also selected by the multi-model ensemble as those most important to the quantitative prediction of several foliar biochemical traits. Patterns of phylogenetic organization of spectra and traits varied across sites and with soil fertility, indicative of the complex interactions between the environmental and phylogenetic controls underlying patterns of biodiversity.

Consistent mutational paths predict eukaryotic thermostability

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van Noort Vera

2013-01-01

Full Text Available Abstract Background Proteomes of thermophilic prokaryotes have been instrumental in structural biology and successfully exploited in biotechnology, however many proteins required for eukaryotic cell function are absent from bacteria or archaea. With Chaetomium thermophilum, Thielavia terrestris and Thielavia heterothallica three genome sequences of thermophilic eukaryotes have been published. Results Studying the genomes and proteomes of these thermophilic fungi, we found common strategies of thermal adaptation across the different kingdoms of Life, including amino acid biases and a reduced genome size. A phylogenetics-guided comparison of thermophilic proteomes with those of other, mesophilic Sordariomycetes revealed consistent amino acid substitutions associated to thermophily that were also present in an independent lineage of thermophilic fungi. The most consistent pattern is the substitution of lysine by arginine, which we could find in almost all lineages but has not been extensively used in protein stability engineering. By exploiting mutational paths towards the thermophiles, we could predict particular amino acid residues in individual proteins that contribute to thermostability and validated some of them experimentally. By determining the three-dimensional structure of an exemplar protein from C. thermophilum (Arx1, we could also characterise the molecular consequences of some of these mutations. Conclusions The comparative analysis of these three genomes not only enhances our understanding of the evolution of thermophily, but also provides new ways to engineer protein stability.

Maximizing the phylogenetic diversity of seed banks.

Science.gov (United States)

Griffiths, Kate E; Balding, Sharon T; Dickie, John B; Lewis, Gwilym P; Pearce, Tim R; Grenyer, Richard

2015-04-01

Ex situ conservation efforts such as those of zoos, botanical gardens, and seed banks will form a vital complement to in situ conservation actions over the coming decades. It is therefore necessary to pay the same attention to the biological diversity represented in ex situ conservation facilities as is often paid to protected-area networks. Building the phylogenetic diversity of ex situ collections will strengthen our capacity to respond to biodiversity loss. Since 2000, the Millennium Seed Bank Partnership has banked seed from 14% of the world's plant species. We assessed the taxonomic, geographic, and phylogenetic diversity of the Millennium Seed Bank collection of legumes (Leguminosae). We compared the collection with all known legume genera, their known geographic range (at country and regional levels), and a genus-level phylogeny of the legume family constructed for this study. Over half the phylogenetic diversity of legumes at the genus level was represented in the Millennium Seed Bank. However, pragmatic prioritization of species of economic importance and endangerment has led to the banking of a less-than-optimal phylogenetic diversity and prioritization of range-restricted species risks an underdispersed collection. The current state of the phylogenetic diversity of legumes in the Millennium Seed Bank could be substantially improved through the strategic banking of relatively few additional taxa. Our method draws on tools that are widely applied to in situ conservation planning, and it can be used to evaluate and improve the phylogenetic diversity of ex situ collections. © 2014 Society for Conservation Biology.

Reconstructing phylogenetic networks using maximum parsimony.

Science.gov (United States)

Nakhleh, Luay; Jin, Guohua; Zhao, Fengmei; Mellor-Crummey, John

2005-01-01

Phylogenies - the evolutionary histories of groups of organisms - are one of the most widely used tools throughout the life sciences, as well as objects of research within systematics, evolutionary biology, epidemiology, etc. Almost every tool devised to date to reconstruct phylogenies produces trees; yet it is widely understood and accepted that trees oversimplify the evolutionary histories of many groups of organims, most prominently bacteria (because of horizontal gene transfer) and plants (because of hybrid speciation). Various methods and criteria have been introduced for phylogenetic tree reconstruction. Parsimony is one of the most widely used and studied criteria, and various accurate and efficient heuristics for reconstructing trees based on parsimony have been devised. Jotun Hein suggested a straightforward extension of the parsimony criterion to phylogenetic networks. In this paper we formalize this concept, and provide the first experimental study of the quality of parsimony as a criterion for constructing and evaluating phylogenetic networks. Our results show that, when extended to phylogenetic networks, the parsimony criterion produces promising results. In a great majority of the cases in our experiments, the parsimony criterion accurately predicts the numbers and placements of non-tree events.

Mapping Phylogenetic Trees to Reveal Distinct Patterns of Evolution.

Science.gov (United States)

Kendall, Michelle; Colijn, Caroline

2016-10-01

Evolutionary relationships are frequently described by phylogenetic trees, but a central barrier in many fields is the difficulty of interpreting data containing conflicting phylogenetic signals. We present a metric-based method for comparing trees which extracts distinct alternative evolutionary relationships embedded in data. We demonstrate detection and resolution of phylogenetic uncertainty in a recent study of anole lizards, leading to alternate hypotheses about their evolutionary relationships. We use our approach to compare trees derived from different genes of Ebolavirus and find that the VP30 gene has a distinct phylogenetic signature composed of three alternatives that differ in the deep branching structure. phylogenetics, evolution, tree metrics, genetics, sequencing. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Combined amplification and hybridization techniques for genome scanning in vegetatively propagated crops

Energy Technology Data Exchange (ETDEWEB)

Kahl, G; Ramser, J; Terauchi, R [Biocentre, University of Frankfurt, Frankfurt am Main (Germany); Lopez-Peralta, C [IRGP, Colegio de Postgraduados, Montecillo, Edo. de Mexico, Texcoco (Mexico); Asemota, H N [Biotechnology Centre, University of the West Indies, Mona, Kingston (Jamaica); Weising, K [School of Biological Sciences, University of Auckland, Auckland (New Zealand)

1998-10-01

A combination of PCR- and hybridization-based genome scanning techniques and sequence comparisons between non-coding chloroplast DNA flanking tRNA genes has been employed to screen Dioscorea species for intra- and interspecific genetic diversity. This methodology detected extensive polymorphisms within Dioscorea bulbifera L., and revealed taxonomic and phylogenetic relationships among cultivated Guinea yams varieties and their potential wild progenitors. Finally, screening of yam germplasm grown in Jamaica permitted reliable discrimination between all major cultivars. Genome scanning by micro satellite-primed PCR (MP-PCR) and random amplified polymorphic DNA (RAPD) analysis in combination with the novel random amplified micro satellite polymorphisms (RAMPO) hybridization technique has shown high potential for the genetic analysis of yams, and holds promise for other vegetatively propagated orphan crops. (author) 46 refs, 3 figs, 3 tabs

Molecular Phylogenetics: Mathematical Framework and Unsolved Problems

Science.gov (United States)

Xia, Xuhua

Phylogenetic relationship is essential in dating evolutionary events, reconstructing ancestral genes, predicting sites that are important to natural selection, and, ultimately, understanding genomic evolution. Three categories of phylogenetic methods are currently used: the distance-based, the maximum parsimony, and the maximum likelihood method. Here, I present the mathematical framework of these methods and their rationales, provide computational details for each of them, illustrate analytically and numerically the potential biases inherent in these methods, and outline computational challenges and unresolved problems. This is followed by a brief discussion of the Bayesian approach that has been recently used in molecular phylogenetics.

Reversible polymorphism-aware phylogenetic models and their application to tree inference.

Science.gov (United States)

Schrempf, Dominik; Minh, Bui Quang; De Maio, Nicola; von Haeseler, Arndt; Kosiol, Carolin

2016-10-21

We present a reversible Polymorphism-Aware Phylogenetic Model (revPoMo) for species tree estimation from genome-wide data. revPoMo enables the reconstruction of large scale species trees for many within-species samples. It expands the alphabet of DNA substitution models to include polymorphic states, thereby, naturally accounting for incomplete lineage sorting. We implemented revPoMo in the maximum likelihood software IQ-TREE. A simulation study and an application to great apes data show that the runtimes of our approach and standard substitution models are comparable but that revPoMo has much better accuracy in estimating trees, divergence times and mutation rates. The advantage of revPoMo is that an increase of sample size per species improves estimations but does not increase runtime. Therefore, revPoMo is a valuable tool with several applications, from speciation dating to species tree reconstruction. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Phylogenetic community structure: temporal variation in fish assemblage

OpenAIRE

Santorelli, Sergio; Magnusson, William; Ferreira, Efrem; Caramaschi, Erica; Zuanon, Jansen; Amadio, Sidnéia

2014-01-01

Hypotheses about phylogenetic relationships among species allow inferences about the mechanisms that affect species coexistence. Nevertheless, most studies assume that phylogenetic patterns identified are stable over time. We used data on monthly samples of fish from a single lake over 10 years to show that the structure in phylogenetic assemblages varies over time and conclusions depend heavily on the time scale investigated. The data set was organized in guild structures and temporal scales...

Using answer set programming to integrate RNA expression with signalling pathway information to infer how mutations affect ageing.

Science.gov (United States)

Papatheodorou, Irene; Ziehm, Matthias; Wieser, Daniela; Alic, Nazif; Partridge, Linda; Thornton, Janet M

2012-01-01

A challenge of systems biology is to integrate incomplete knowledge on pathways with existing experimental data sets and relate these to measured phenotypes. Research on ageing often generates such incomplete data, creating difficulties in integrating RNA expression with information about biological processes and the phenotypes of ageing, including longevity. Here, we develop a logic-based method that employs Answer Set Programming, and use it to infer signalling effects of genetic perturbations, based on a model of the insulin signalling pathway. We apply our method to RNA expression data from Drosophila mutants in the insulin pathway that alter lifespan, in a foxo dependent fashion. We use this information to deduce how the pathway influences lifespan in the mutant animals. We also develop a method for inferring the largest common sub-paths within each of our signalling predictions. Our comparisons reveal consistent homeostatic mechanisms across both long- and short-lived mutants. The transcriptional changes observed in each mutation usually provide negative feedback to signalling predicted for that mutation. We also identify an S6K-mediated feedback in two long-lived mutants that suggests a crosstalk between these pathways in mutants of the insulin pathway, in vivo. By formulating the problem as a logic-based theory in a qualitative fashion, we are able to use the efficient search facilities of Answer Set Programming, allowing us to explore larger pathways, combine molecular changes with pathways and phenotype and infer effects on signalling in in vivo, whole-organism, mutants, where direct signalling stimulation assays are difficult to perform. Our methods are available in the web-service NetEffects: http://www.ebi.ac.uk/thornton-srv/software/NetEffects.

Comparative morphology of premolar foramen in lagomorphs (Mammalia: Glires and its functional and phylogenetic implications.

Directory of Open Access Journals (Sweden)

Łucja Fostowicz-Frelik

Full Text Available Lagomorphs (a group that consists of pikas, hares, rabbits and allies are notable for their conservative morphology retained for most of their over 50 million years evolutionary history. On the other hand, their remarkable morphological uniformity partly stems from a considerable number of homoplasies in cranial and dental structures that hamper phylogenetic analyses. The premolar foramen, an opening in the palate of lagomorphs, has been characterized as an important synapomorphy of one clade, Ochotonidae (pikas. Within Lagomorpha, however, its phylogenetic distribution is much wider, the foramen being present not only in all ochotonids but also in leporids and stem taxa; its morphology and incidence also varies considerably across the order, even intraspecifically. In this study, we provide a broad survey of the taxonomic distribution of the premolar foramen in extant and fossil Lagomorpha and describe in detail the morphological variation of this character within the group. Micro-computed tomography was used to examine the hard palate and infraorbital groove morphology in Poelagus (Leporidae and Ochotona. Scans revealed the course and contacts of the canal behind the premolar foramen and structural differences between the two crown clades. We propose that the premolar foramen has evolved independently in several lineages of Lagomorpha, and we discuss development and function of this foramen in the lagomorph skull. This study shows the importance of comprehensive studies on phylogenetically informative non-dental characters in Lagomorpha.

Mutations in DNA repair genes are associated with the Haarlem lineage of Mycobacterium tuberculosis independently of their antibiotic resistance.

Science.gov (United States)

Olano, Juanita; López, Beatriz; Reyes, Alejandro; Lemos, María del Pilar; Correa, Nidia; Del Portillo, Patricia; Barrera, Lucia; Robledo, Jaime; Ritacco, Viviana; Zambrano, María Mercedes

2007-11-01

The analysis of the DNA repair genes ogt and ung was carried out in 117 Mycobacterium tuberculosis clinical isolates from Argentina and Colombia in order to explore correlation between mutations in these genes and multi-drug resistance. With the exception of two Beijing family isolates, the rest of the strains harbored either two wild-type or two mutant alleles with identical single nucleotide polymorphisms (SNPs) in each gene (ogt44 and ung501). These ogt44 and ung501 mutations were not associated with multi-drug resistance and occurred simultaneously in circulating Haarlem genotype M. tuberculosis strains. We therefore propose the use of these markers as tools in phylogenetic and epidemiologic studies.

Exploring the Genomic Roadmap and Molecular Phylogenetics Associated with MODY Cascades Using Computational Biology.

Science.gov (United States)

Chakraborty, Chiranjib; Bandyopadhyay, Sanghamitra; Doss, C George Priya; Agoramoorthy, Govindasamy

2015-04-01

Maturity onset diabetes of the young (MODY) is a metabolic and genetic disorder. It is different from type 1 and type 2 diabetes with low occurrence level (1-2%) among all diabetes. This disorder is a consequence of β-cell dysfunction. Till date, 11 subtypes of MODY have been identified, and all of them can cause gene mutations. However, very little is known about the gene mapping, molecular phylogenetics, and co-expression among MODY genes and networking between cascades. This study has used latest servers and software such as VarioWatch, ClustalW, MUSCLE, G Blocks, Phylogeny.fr, iTOL, WebLogo, STRING, and KEGG PATHWAY to perform comprehensive analyses of gene mapping, multiple sequences alignment, molecular phylogenetics, protein-protein network design, co-expression analysis of MODY genes, and pathway development. The MODY genes are located in chromosomes-2, 7, 8, 9, 11, 12, 13, 17, and 20. Highly aligned block shows Pro, Gly, Leu, Arg, and Pro residues are highly aligned in the positions of 296, 386, 437, 455, 456 and 598, respectively. Alignment scores inform us that HNF1A and HNF1B proteins have shown high sequence similarity among MODY proteins. Protein-protein network design shows that HNF1A, HNF1B, HNF4A, NEUROD1, PDX1, PAX4, INS, and GCK are strongly connected, and the co-expression analyses between MODY genes also show distinct association between HNF1A and HNF4A genes. This study has used latest tools of bioinformatics to develop a rapid method to assess the evolutionary relationship, the network development, and the associations among eleven MODY genes and cascades. The prediction of sequence conservation, molecular phylogenetics, protein-protein network and the association between the MODY cascades enhances opportunities to get more insights into the less-known MODY disease.

Virulence, serotype and phylogenetic groups of diarrhoeagenic ...

African Journals Online (AJOL)

Dr DADIE Thomas

2014-02-17

Feb 17, 2014 ... The virulence, serotype and phylogenetic traits of diarrhoeagenic Escherichia coli were detected in 502 strains isolated during digestive infections. Molecular detection of the target virulence genes, rfb gene of operon O and phylogenetic grouping genes Chua, yjaA and TSPE4.C2 was performed.

X-ray scan detection for cargo integrity

Science.gov (United States)

Valencia, Juan; Miller, Steve

2011-04-01

The increase of terrorism and its global impact has made the determination of the contents of cargo containers a necessity. Existing technology allows non-intrusive inspections to determine the contents of a container rapidly and accurately. However, some cargo shipments are exempt from such inspections. Hence, there is a need for a technology that enables rapid and accurate means of detecting whether such containers were non-intrusively inspected. Non-intrusive inspections are most commonly performed utilizing high powered X-ray equipment. The challenge is creating a device that can detect short duration X-ray scans while maintaining a portable, battery powered, low cost, and easy to use platform. The Pacific Northwest National Laboratory (PNNL) has developed a methodology and prototype device focused on this challenge. The prototype, developed by PNNL, is a battery powered electronic device that continuously measures its X-ray and Gamma exposure, calculates the dose equivalent rate, and makes a determination of whether the device has been exposed to the amount of radiation experienced during an X-ray inspection. Once an inspection is detected, the device will record a timestamp of the event and relay the information to authorized personnel via a visual alert, USB connection, and/or wireless communication. The results of this research demonstrate that PNNL's prototype device can be effective at determining whether a container was scanned by X-ray equipment typically used for cargo container inspections. This paper focuses on laboratory measurements and test results acquired with the PNNL prototype device using several X-ray radiation levels.

["Long-branch Attraction" artifact in phylogenetic reconstruction].

Science.gov (United States)

Li, Yi-Wei; Yu, Li; Zhang, Ya-Ping

2007-06-01

Phylogenetic reconstruction among various organisms not only helps understand their evolutionary history but also reveal several fundamental evolutionary questions. Understanding of the evolutionary relationships among organisms establishes the foundation for the investigations of other biological disciplines. However, almost all the widely used phylogenetic methods have limitations which fail to eliminate systematic errors effectively, preventing the reconstruction of true organismal relationships. "Long-branch Attraction" (LBA) artifact is one of the most disturbing factors in phylogenetic reconstruction. In this review, the conception and analytic method as well as the avoidance strategy of LBA were summarized. In addition, several typical examples were provided. The approach to avoid and resolve LBA artifact has been discussed.

From learning taxonomies to phylogenetic learning: Integration of 16S rRNA gene data into FAME-based bacterial classification

Science.gov (United States)

2010-01-01

Background Machine learning techniques have shown to improve bacterial species classification based on fatty acid methyl ester (FAME) data. Nonetheless, FAME analysis has a limited resolution for discrimination of bacteria at the species level. In this paper, we approach the species classification problem from a taxonomic point of view. Such a taxonomy or tree is typically obtained by applying clustering algorithms on FAME data or on 16S rRNA gene data. The knowledge gained from the tree can then be used to evaluate FAME-based classifiers, resulting in a novel framework for bacterial species classification. Results In view of learning in a taxonomic framework, we consider two types of trees. First, a FAME tree is constructed with a supervised divisive clustering algorithm. Subsequently, based on 16S rRNA gene sequence analysis, phylogenetic trees are inferred by the NJ and UPGMA methods. In this second approach, the species classification problem is based on the combination of two different types of data. Herein, 16S rRNA gene sequence data is used for phylogenetic tree inference and the corresponding binary tree splits are learned based on FAME data. We call this learning approach 'phylogenetic learning'. Supervised Random Forest models are developed to train the classification tasks in a stratified cross-validation setting. In this way, better classification results are obtained for species that are typically hard to distinguish by a single or flat multi-class classification model. Conclusions FAME-based bacterial species classification is successfully evaluated in a taxonomic framework. Although the proposed approach does not improve the overall accuracy compared to flat multi-class classification, it has some distinct advantages. First, it has better capabilities for distinguishing species on which flat multi-class classification fails. Secondly, the hierarchical classification structure allows to easily evaluate and visualize the resolution of FAME data for

From learning taxonomies to phylogenetic learning: Integration of 16S rRNA gene data into FAME-based bacterial classification

Directory of Open Access Journals (Sweden)

Dawyndt Peter

2010-01-01

Full Text Available Abstract Background Machine learning techniques have shown to improve bacterial species classification based on fatty acid methyl ester (FAME data. Nonetheless, FAME analysis has a limited resolution for discrimination of bacteria at the species level. In this paper, we approach the species classification problem from a taxonomic point of view. Such a taxonomy or tree is typically obtained by applying clustering algorithms on FAME data or on 16S rRNA gene data. The knowledge gained from the tree can then be used to evaluate FAME-based classifiers, resulting in a novel framework for bacterial species classification. Results In view of learning in a taxonomic framework, we consider two types of trees. First, a FAME tree is constructed with a supervised divisive clustering algorithm. Subsequently, based on 16S rRNA gene sequence analysis, phylogenetic trees are inferred by the NJ and UPGMA methods. In this second approach, the species classification problem is based on the combination of two different types of data. Herein, 16S rRNA gene sequence data is used for phylogenetic tree inference and the corresponding binary tree splits are learned based on FAME data. We call this learning approach 'phylogenetic learning'. Supervised Random Forest models are developed to train the classification tasks in a stratified cross-validation setting. In this way, better classification results are obtained for species that are typically hard to distinguish by a single or flat multi-class classification model. Conclusions FAME-based bacterial species classification is successfully evaluated in a taxonomic framework. Although the proposed approach does not improve the overall accuracy compared to flat multi-class classification, it has some distinct advantages. First, it has better capabilities for distinguishing species on which flat multi-class classification fails. Secondly, the hierarchical classification structure allows to easily evaluate and visualize the

From learning taxonomies to phylogenetic learning: integration of 16S rRNA gene data into FAME-based bacterial classification.

Science.gov (United States)

Slabbinck, Bram; Waegeman, Willem; Dawyndt, Peter; De Vos, Paul; De Baets, Bernard

2010-01-30

Machine learning techniques have shown to improve bacterial species classification based on fatty acid methyl ester (FAME) data. Nonetheless, FAME analysis has a limited resolution for discrimination of bacteria at the species level. In this paper, we approach the species classification problem from a taxonomic point of view. Such a taxonomy or tree is typically obtained by applying clustering algorithms on FAME data or on 16S rRNA gene data. The knowledge gained from the tree can then be used to evaluate FAME-based classifiers, resulting in a novel framework for bacterial species classification. In view of learning in a taxonomic framework, we consider two types of trees. First, a FAME tree is constructed with a supervised divisive clustering algorithm. Subsequently, based on 16S rRNA gene sequence analysis, phylogenetic trees are inferred by the NJ and UPGMA methods. In this second approach, the species classification problem is based on the combination of two different types of data. Herein, 16S rRNA gene sequence data is used for phylogenetic tree inference and the corresponding binary tree splits are learned based on FAME data. We call this learning approach 'phylogenetic learning'. Supervised Random Forest models are developed to train the classification tasks in a stratified cross-validation setting. In this way, better classification results are obtained for species that are typically hard to distinguish by a single or flat multi-class classification model. FAME-based bacterial species classification is successfully evaluated in a taxonomic framework. Although the proposed approach does not improve the overall accuracy compared to flat multi-class classification, it has some distinct advantages. First, it has better capabilities for distinguishing species on which flat multi-class classification fails. Secondly, the hierarchical classification structure allows to easily evaluate and visualize the resolution of FAME data for the discrimination of bacterial

An integrative genomic and proteomic analysis of PIK3CA, PTEN and AKT mutations in breast cancer

Energy Technology Data Exchange (ETDEWEB)

Stemke-Hale, Katherine; Gonzalez-Angulo, Ana Maria; Lluch, Ana; Neve, Richard M.; Kuo, Wen-Lin; Davies, Michael; Carey, Mark; Hu, Zhi; Guan, Yinghui; Sahin, Aysegul; Symmans, W. Fraser; Pusztai, Lajos; Nolden, Laura K.; Horlings, Hugo; Berns, Katrien; Hung, Mien-Chie; van de Vijver, Marc J.; Valero, Vicente; Gray, Joe W.; Bernards, Rene; Mills, Gordon B.; Hennessy, Bryan T.

2008-05-06

Phosphatidylinositol-3-kinase (PI3K)/AKT pathway aberrations are common in cancer. By applying mass spectroscopy-based sequencing and reverse phase protein arrays to 547 human breast cancers and 41 cell lines, we determined the subtype specificity and signaling effects of PIK3CA, AKT and PTEN mutations, and the effects of PIK3CA mutations on responsiveness to PI3K inhibition in-vitro and on outcome after adjuvant tamoxifen. PIK3CA mutations were more common in hormone receptor positive (33.8%) and HER2-positive (24.6%) than in basal-like tumors (8.3%). AKT1 (1.4%) and PTEN (2.3%) mutations were restricted to hormone receptor-positive cancers with PTEN protein levels also being significantly lower in hormone receptor-positive cancers. Unlike AKT1 mutations, PIK3CA (39%) and PTEN (20%) mutations were more common in cell lines than tumors, suggesting a selection for these but not AKT1 mutations during adaptation to culture. PIK3CA mutations did not have a significant impact on outcome in 166 hormone receptor-positive breast cancer patients after adjuvant tamoxifen. PIK3CA mutations, in comparison with PTEN loss and AKT1 mutations, were associated with significantly less and indeed inconsistent activation of AKT and of downstream PI3K/AKT signaling in tumors and cell lines, and PTEN loss and PIK3CA mutation were frequently concordant, suggesting different contributions to pathophysiology. PTEN loss but not PIK3CA mutations rendered cells sensitive to growth inhibition by the PI3K inhibitor LY294002. Thus, PI3K pathway aberrations likely play a distinct role in the pathogenesis of different breast cancer subtypes. The specific aberration may have implications for the selection of PI3K-targeted therapies in hormone receptor-positive breast cancer.

Bone scan in pediatrics

International Nuclear Information System (INIS)

Gordon, I.; Peters, A.M.

1987-01-01

In 1984, a survey carried out in 21 countries in Europe showed that bone scintigraphy comprised 16% of all paediatric radioisotope scans. Although the value of bone scans in paediatrics is potentially great, their quality varies greatly, and poor-quality images are giving this valuable technique a bad reputation. The handling of children requires a sensitive staff and the provision of a few simple inexpensive items of distraction. Attempting simply to scan a child between two adult patients in a busy general department is a recipe for an unhappy, uncooperative child with the probable result of poor images. The intravenous injection of isotope should be given adjacent to the gamma camera room, unless dynamic scans are required, so that the child does not associate the camera with the injection. This injection is best carried out by someone competent in paediatric venipunture; the entire procedure should be explained to the child and parent, who should remain with child throughout. It is naive to think that silence makes for a cooperative child. The sensitivity of bone-seeking radioisotope tracers and the marked improvement in gamma camera resolution has allowed the bone scanning to become an integrated technique in the assessment of children suspected of suffering from pathological bone conditions. The tracer most commonly used for routine bone scanning is 99m Tc diphosphonate (MDP); other isotopes used include 99m Tc colloid for bone marrow scans and 67 Ga citrate and 111 In white blood cells ( 111 In WBC) for investigation of inflammatory/infective lesions

Phylogenetically Acquired Representations and Evolutionary Algorithms.

OpenAIRE

Wozniak , Adrianna

2006-01-01

First, we explain why Genetic Algorithms (GAs), inspired by the Modern Synthesis, do not accurately model biological evolution, being rather an artificial version of artificial, rather than natural selection. Being focused on optimisation, we propose two improvements of GAs, with the aim to successfully generate adapted, desired behaviour. The first one concerns phylogenetic grounding of meaning, a way to avoid the Symbol Grounding Problem. We give a definition of Phylogenetically Acquired Re...

Establishing a framework for comparative analysis of genome sequences

Energy Technology Data Exchange (ETDEWEB)

Bansal, A.K.

1995-06-01

This paper describes a framework and a high-level language toolkit for comparative analysis of genome sequence alignment The framework integrates the information derived from multiple sequence alignment and phylogenetic tree (hypothetical tree of evolution) to derive new properties about sequences. Multiple sequence alignments are treated as an abstract data type. Abstract operations have been described to manipulate a multiple sequence alignment and to derive mutation related information from a phylogenetic tree by superimposing parsimonious analysis. The framework has been applied on protein alignments to derive constrained columns (in a multiple sequence alignment) that exhibit evolutionary pressure to preserve a common property in a column despite mutation. A Prolog toolkit based on the framework has been implemented and demonstrated on alignments containing 3000 sequences and 3904 columns.

Sequence analysis of the L protein of the Ebola 2014 outbreak: Insight into conserved regions and mutations.

Science.gov (United States)

Ayub, Gohar; Waheed, Yasir

2016-06-01

The 2014 Ebola outbreak was one of the largest that have occurred; it started in Guinea and spread to Nigeria, Liberia and Sierra Leone. Phylogenetic analysis of the current virus species indicated that this outbreak is the result of a divergent lineage of the Zaire ebolavirus. The L protein of Ebola virus (EBOV) is the catalytic subunit of the RNA‑dependent RNA polymerase complex, which, with VP35, is key for the replication and transcription of viral RNA. Earlier sequence analysis demonstrated that the L protein of all non‑segmented negative‑sense (NNS) RNA viruses consists of six domains containing conserved functional motifs. The aim of the present study was to analyze the presence of these motifs in 2014 EBOV isolates, highlight their function and how they may contribute to the overall pathogenicity of the isolates. For this purpose, 81 2014 EBOV L protein sequences were aligned with 475 other NNS RNA viruses, including Paramyxoviridae and Rhabdoviridae viruses. Phylogenetic analysis of all EBOV outbreak L protein sequences was also performed. Analysis of the amino acid substitutions in the 2014 EBOV outbreak was conducted using sequence analysis. The alignment demonstrated the presence of previously conserved motifs in the 2014 EBOV isolates and novel residues. Notably, all the mutations identified in the 2014 EBOV isolates were tolerant, they were pathogenic with certain examples occurring within previously determined functional conserved motifs, possibly altering viral pathogenicity, replication and virulence. The phylogenetic analysis demonstrated that all sequences with the exception of the 2014 EBOV sequences were clustered together. The 2014 EBOV outbreak has acquired a great number of mutations, which may explain the reasons behind this unprecedented outbreak. Certain residues critical to the function of the polymerase remain conserved and may be targets for the development of antiviral therapeutic agents.

A program to compute the soft Robinson-Foulds distance between phylogenetic networks.

Science.gov (United States)

Lu, Bingxin; Zhang, Louxin; Leong, Hon Wai

2017-03-14

Over the past two decades, phylogenetic networks have been studied to model reticulate evolutionary events. The relationships among phylogenetic networks, phylogenetic trees and clusters serve as the basis for reconstruction and comparison of phylogenetic networks. To understand these relationships, two problems are raised: the tree containment problem, which asks whether a phylogenetic tree is displayed in a phylogenetic network, and the cluster containment problem, which asks whether a cluster is represented at a node in a phylogenetic network. Both the problems are NP-complete. A fast exponential-time algorithm for the cluster containment problem on arbitrary networks is developed and implemented in C. The resulting program is further extended into a computer program for fast computation of the Soft Robinson-Foulds distance between phylogenetic networks. Two computer programs are developed for facilitating reconstruction and validation of phylogenetic network models in evolutionary and comparative genomics. Our simulation tests indicated that they are fast enough for use in practice. Additionally, the distribution of the Soft Robinson-Foulds distance between phylogenetic networks is demonstrated to be unlikely normal by our simulation data.

Mitochondrial C4375T mutation might be a molecular risk factor in a maternal Chinese hypertensive family under haplotype C.

Science.gov (United States)

Chen, Hong; Sun, Min; Fan, Zhen; Tong, Maoqing; Chen, Guodong; Li, Danhui; Ye, Jihui; Yang, Yumin; Zhu, Yongding; Zhu, Jianhua

2017-12-04

Here, we reported a Han Chinese essential hypertensive pedigree based on clinical hereditary and molecular data. To know the molecular basis on this family, mitochondrial genome of one proband from the family was identified through direct sequencing analysis. The age of onset year and affected degree of patients are different in this family. And matrilineal family members carrying C4375T mutation and belong to Eastern Asian halopgroup C. Phylogenetic analysis shows 4375C is highly conservative in 17 species. It is suggested that these mutations might participate in the development of hypertension in this family. And halopgroup C might play a modifying role on the phenotype in this Chinese hypertensive family.

Molecular Phylogenetic: Organism Taxonomy Method Based on Evolution History

Directory of Open Access Journals (Sweden)

N.L.P Indi Dharmayanti

2011-03-01

Full Text Available Phylogenetic is described as taxonomy classification of an organism based on its evolution history namely its phylogeny and as a part of systematic science that has objective to determine phylogeny of organism according to its characteristic. Phylogenetic analysis from amino acid and protein usually became important area in sequence analysis. Phylogenetic analysis can be used to follow the rapid change of a species such as virus. The phylogenetic evolution tree is a two dimensional of a species graphic that shows relationship among organisms or particularly among their gene sequences. The sequence separation are referred as taxa (singular taxon that is defined as phylogenetically distinct units on the tree. The tree consists of outer branches or leaves that represents taxa and nodes and branch represent correlation among taxa. When the nucleotide sequence from two different organism are similar, they were inferred to be descended from common ancestor. There were three methods which were used in phylogenetic, namely (1 Maximum parsimony, (2 Distance, and (3 Maximum likehoood. Those methods generally are applied to construct the evolutionary tree or the best tree for determine sequence variation in group. Every method is usually used for different analysis and data.

Morphological reassessment and molecular phylogenetic analyses of Amauroderma s.lat. raised new perspectives in the generic classification of the Ganodermataceae family

NARCIS (Netherlands)

Costa-Rezende, D.H.; Robledo, G.L.; Góes-Neto, A.; Reck, M.A.; Crespo, E.; Drechsler-Santos, E.R.

2017-01-01

Ganodermataceae is a remarkable group of polypore fungi, mainly characterized by particular doublewalled basidiospores with a coloured endosporium ornamented with columns or crests, and a hyaline smooth exosporium. In order to establish an integrative morphological and molecular phylogenetic

A HRM assay for identification of low level BRAF V600E and V600K mutations using the CADMA principle in FFPE specimens.

Science.gov (United States)

Huebner, Claudia; Weber, Remeny; Lloydd, Richard

2017-12-01

Melanoma patients with BRAF V600E and V600K mutations show complete or partial response to vemurafenib. Detection assays often scan for the common V600E mutation rather than the rare V600K variant, although this mutation can be found in a high proportion of melanoma patients in the South Pacific. Herein, we describe a BRAF high resolution melting (HRM) assay that can differentiate low level of V600E and V600K mutations using formalin fixed, paraffin embedded (FFPE) reference standards for assay validation. The assay is based on the competitive amplification of differentially melting amplicons (CADMA principle) and has a limit of detection of 0.8% mutant allele for V600K and 1.4% mutant allele for V600E. A differentiation between the two mutations based on the melting profile is possible even at low mutation level. Sixty FFPE specimens were scanned and mutations could be scored correctly as confirmed by castPCR. In summary, the developed HRM assay is suitable for detection of V600K and V600E mutations and proved to be reliable and cost effective in a diagnostic environment. Copyright © 2017 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

Disentangling the phylogenetic and ecological components of spider phenotypic variation.

Science.gov (United States)

Gonçalves-Souza, Thiago; Diniz-Filho, José Alexandre Felizola; Romero, Gustavo Quevedo

2014-01-01

An understanding of how the degree of phylogenetic relatedness influences the ecological similarity among species is crucial to inferring the mechanisms governing the assembly of communities. We evaluated the relative importance of spider phylogenetic relationships and ecological niche (plant morphological variables) to the variation in spider body size and shape by comparing spiders at different scales: (i) between bromeliads and dicot plants (i.e., habitat scale) and (ii) among bromeliads with distinct architectural features (i.e., microhabitat scale). We partitioned the interspecific variation in body size and shape into phylogenetic (that express trait values as expected by phylogenetic relationships among species) and ecological components (that express trait values independent of phylogenetic relationships). At the habitat scale, bromeliad spiders were larger and flatter than spiders associated with the surrounding dicots. At this scale, plant morphology sorted out close related spiders. Our results showed that spider flatness is phylogenetically clustered at the habitat scale, whereas it is phylogenetically overdispersed at the microhabitat scale, although phylogenic signal is present in both scales. Taken together, these results suggest that whereas at the habitat scale selective colonization affect spider body size and shape, at fine scales both selective colonization and adaptive evolution determine spider body shape. By partitioning the phylogenetic and ecological components of phenotypic variation, we were able to disentangle the evolutionary history of distinct spider traits and show that plant architecture plays a role in the evolution of spider body size and shape. We also discussed the relevance in considering multiple scales when studying phylogenetic community structure.

Phylogenetic system and zoogeography of the Plecoptera.

Science.gov (United States)

Zwick, P

2000-01-01

Information about the phylogenetic relationships of Plecoptera is summarized. The few characters supporting monophyly of the order are outlined. Several characters of possible significance for the search for the closest relatives of the stoneflies are discussed, but the sister-group of the order remains unknown. Numerous characters supporting the presently recognized phylogenetic system of Plecoptera are presented, alternative classifications are discussed, and suggestions for future studies are made. Notes on zoogeography are appended. The order as such is old (Permian fossils), but phylogenetic relationships and global distribution patterns suggest that evolution of the extant suborders started with the breakup of Pangaea. There is evidence of extensive recent speciation in all parts of the world.

Cophenetic metrics for phylogenetic trees, after Sokal and Rohlf.

Science.gov (United States)

Cardona, Gabriel; Mir, Arnau; Rosselló, Francesc; Rotger, Lucía; Sánchez, David

2013-01-16

Phylogenetic tree comparison metrics are an important tool in the study of evolution, and hence the definition of such metrics is an interesting problem in phylogenetics. In a paper in Taxon fifty years ago, Sokal and Rohlf proposed to measure quantitatively the difference between a pair of phylogenetic trees by first encoding them by means of their half-matrices of cophenetic values, and then comparing these matrices. This idea has been used several times since then to define dissimilarity measures between phylogenetic trees but, to our knowledge, no proper metric on weighted phylogenetic trees with nested taxa based on this idea has been formally defined and studied yet. Actually, the cophenetic values of pairs of different taxa alone are not enough to single out phylogenetic trees with weighted arcs or nested taxa. For every (rooted) phylogenetic tree T, let its cophenetic vectorφ(T) consist of all pairs of cophenetic values between pairs of taxa in T and all depths of taxa in T. It turns out that these cophenetic vectors single out weighted phylogenetic trees with nested taxa. We then define a family of cophenetic metrics dφ,p by comparing these cophenetic vectors by means of Lp norms, and we study, either analytically or numerically, some of their basic properties: neighbors, diameter, distribution, and their rank correlation with each other and with other metrics. The cophenetic metrics can be safely used on weighted phylogenetic trees with nested taxa and no restriction on degrees, and they can be computed in O(n2) time, where n stands for the number of taxa. The metrics dφ,1 and dφ,2 have positive skewed distributions, and they show a low rank correlation with the Robinson-Foulds metric and the nodal metrics, and a very high correlation with each other and with the splitted nodal metrics. The diameter of dφ,p, for p⩾1 , is in O(n(p+2)/p), and thus for low p they are more discriminative, having a wider range of values.

The best of both worlds: Phylogenetic eigenvector regression and mapping

Directory of Open Access Journals (Sweden)

José Alexandre Felizola Diniz Filho

2015-09-01

Full Text Available Eigenfunction analyses have been widely used to model patterns of autocorrelation in time, space and phylogeny. In a phylogenetic context, Diniz-Filho et al. (1998 proposed what they called Phylogenetic Eigenvector Regression (PVR, in which pairwise phylogenetic distances among species are submitted to a Principal Coordinate Analysis, and eigenvectors are then used as explanatory variables in regression, correlation or ANOVAs. More recently, a new approach called Phylogenetic Eigenvector Mapping (PEM was proposed, with the main advantage of explicitly incorporating a model-based warping in phylogenetic distance in which an Ornstein-Uhlenbeck (O-U process is fitted to data before eigenvector extraction. Here we compared PVR and PEM in respect to estimated phylogenetic signal, correlated evolution under alternative evolutionary models and phylogenetic imputation, using simulated data. Despite similarity between the two approaches, PEM has a slightly higher prediction ability and is more general than the original PVR. Even so, in a conceptual sense, PEM may provide a technique in the best of both worlds, combining the flexibility of data-driven and empirical eigenfunction analyses and the sounding insights provided by evolutionary models well known in comparative analyses.

Multiple Recurrent Paraganglioma in a Pediatric Patient with Germline SDH-B Mutation

Directory of Open Access Journals (Sweden)

Aidan McGowan

2017-07-01

Full Text Available Magnetic Resonance Imaging (MRI and fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET are recognized approaches for locating paragangliomas. Recently, gallium-68 DOTA-octreotate (DOTATATE scans have shown promise detecting neuroendocrine tumors missed by FDG-PET and MRI. 13-year-old male with SDH-B mutation presented with symptoms of paraganglioma and elevated catecholamines. MRI did not demonstrate the T2 hyper intense signal typical of paraganglioma and pheochromocytoma; FDG-PET scan did not reveal increased foci of uptake. DOTATATE scan revealed a signal consistent only with residual adrenal tissue. Resection of the right adrenal bed revealed paraganglioma. Following surgery, no further symptoms were reported and biochemical tests normalized.

Phylogenetic Analyses of Armillaria Reveal at Least 15 Phylogenetic Lineages in China, Seven of Which Are Associated with Cultivated Gastrodia elata.

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Ting Guo

Full Text Available Fungal species of Armillaria, which can act as plant pathogens and/or symbionts of the Chinese traditional medicinal herb Gastrodia elata ("Tianma", are ecologically and economically important and have consequently attracted the attention of mycologists. However, their taxonomy has been highly dependent on morphological characterization and mating tests. In this study, we phylogenetically analyzed Chinese Armillaria samples using the sequences of the internal transcribed spacer region, translation elongation factor-1 alpha gene and beta-tubulin gene. Our data revealed at least 15 phylogenetic lineages of Armillaria from China, of which seven were newly discovered and two were recorded from China for the first time. Fourteen Chinese biological species of Armillaria, which were previously defined based on mating tests, could be assigned to the 15 phylogenetic lineages identified herein. Seven of the 15 phylogenetic lineages were found to be disjunctively distributed in different continents of the Northern Hemisphere, while eight were revealed to be endemic to certain continents. In addition, we found that seven phylogenetic lineages of Armillaria were used for the cultivation of Tianma, only two of which had been recorded to be associated with Tianma previously. We also illustrated that G. elata f. glauca ("Brown Tianma" and G. elata f. elata ("Red Tianma", two cultivars of Tianma grown in different regions of China, form symbiotic relationships with different phylogenetic lineages of Armillaria. These findings should aid the development of Tianma cultivation in China.

Phylogenetic relationships within and among Brassica species from ...

African Journals Online (AJOL)

Consequently, two potentially susceptible B. napus accessions were identified. The high polymorphic information content (PIC) and number of phylogenetically informative bands established RAPD as a useful tool for phylogenetic reconstruction, quantification of genetic diversity for conservation, cultivar classification and ...

Reconstructing the Phylogenetic History of Long-Term Effective Population Size and Life-History Traits Using Patterns of Amino Acid Replacement in Mitochondrial Genomes of Mammals and Birds

Science.gov (United States)

Nabholz, Benoit; Lartillot, Nicolas

2013-01-01

The nearly neutral theory, which proposes that most mutations are deleterious or close to neutral, predicts that the ratio of nonsynonymous over synonymous substitution rates (dN/dS), and potentially also the ratio of radical over conservative amino acid replacement rates (Kr/Kc), are negatively correlated with effective population size. Previous empirical tests, using life-history traits (LHT) such as body-size or generation-time as proxies for population size, have been consistent with these predictions. This suggests that large-scale phylogenetic reconstructions of dN/dS or Kr/Kc might reveal interesting macroevolutionary patterns in the variation in effective population size among lineages. In this work, we further develop an integrative probabilistic framework for phylogenetic covariance analysis introduced previously, so as to estimate the correlation patterns between dN/dS, Kr/Kc, and three LHT, in mitochondrial genomes of birds and mammals. Kr/Kc displays stronger and more stable correlations with LHT than does dN/dS, which we interpret as a greater robustness of Kr/Kc, compared with dN/dS, the latter being confounded by the high saturation of the synonymous substitution rate in mitochondrial genomes. The correlation of Kr/Kc with LHT was robust when controlling for the potentially confounding effects of nucleotide compositional variation between taxa. The positive correlation of the mitochondrial Kr/Kc with LHT is compatible with previous reports, and with a nearly neutral interpretation, although alternative explanations are also possible. The Kr/Kc model was finally used for reconstructing life-history evolution in birds and mammals. This analysis suggests a fairly large-bodied ancestor in both groups. In birds, life-history evolution seems to have occurred mainly through size reduction in Neoavian birds, whereas in placental mammals, body mass evolution shows disparate trends across subclades. Altogether, our work represents a further step toward a more

Phylogenetic Inference of HIV Transmission Clusters

Directory of Open Access Journals (Sweden)

Vlad Novitsky

2017-10-01

Full Text Available Better understanding the structure and dynamics of HIV transmission networks is essential for designing the most efficient interventions to prevent new HIV transmissions, and ultimately for gaining control of the HIV epidemic. The inference of phylogenetic relationships and the interpretation of results rely on the definition of the HIV transmission cluster. The definition of the HIV cluster is complex and dependent on multiple factors, including the design of sampling, accuracy of sequencing, precision of sequence alignment, evolutionary models, the phylogenetic method of inference, and specified thresholds for cluster support. While the majority of studies focus on clusters, non-clustered cases could also be highly informative. A new dimension in the analysis of the global and local HIV epidemics is the concept of phylogenetically distinct HIV sub-epidemics. The identification of active HIV sub-epidemics reveals spreading viral lineages and may help in the design of targeted interventions.HIVclustering can also be affected by sampling density. Obtaining a proper sampling density may increase statistical power and reduce sampling bias, so sampling density should be taken into account in study design and in interpretation of phylogenetic results. Finally, recent advances in long-range genotyping may enable more accurate inference of HIV transmission networks. If performed in real time, it could both inform public-health strategies and be clinically relevant (e.g., drug-resistance testing.

Phylogenetic and structural diversity in the feline leukemia virus env gene.

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Shinya Watanabe

Full Text Available Feline leukemia virus (FeLV belongs to the genus Gammaretrovirus, and causes a variety of neoplastic and non-neoplastic diseases in cats. Alteration of viral env sequences is thought to be associated with disease specificity, but the way in which genetic diversity of FeLV contributes to the generation of such variants in nature is poorly understood. We isolated FeLV env genes from naturally infected cats in Japan and analyzed the evolutionary dynamics of these genes. Phylogenetic reconstructions separated our FeLV samples into three distinct genetic clusters, termed Genotypes I, II, and III. Genotype I is a major genetic cluster and can be further classified into Clades 1-7 in Japan. Genotypes were correlated with geographical distribution; Genotypes I and II were distributed within Japan, whilst FeLV samples from outside Japan belonged to Genotype III. These results may be due to geographical isolation of FeLVs in Japan. The observed structural diversity of the FeLV env gene appears to be caused primarily by mutation, deletion, insertion and recombination, and these variants may be generated de novo in individual cats. FeLV interference assay revealed that FeLV genotypes did not correlate with known FeLV receptor subgroups. We have identified the genotypes which we consider to be reliable for evaluating phylogenetic relationships of FeLV, which embrace the high structural diversity observed in our sample. Overall, these findings extend our understanding of Gammaretrovirus evolutionary patterns in the field, and may provide a useful basis for assessing the emergence of novel strains and understanding the molecular mechanisms of FeLV transmission in cats.

Visualising very large phylogenetic trees in three dimensional hyperbolic space

Directory of Open Access Journals (Sweden)

Liberles David A

2004-04-01

Full Text Available Abstract Background Common existing phylogenetic tree visualisation tools are not able to display readable trees with more than a few thousand nodes. These existing methodologies are based in two dimensional space. Results We introduce the idea of visualising phylogenetic trees in three dimensional hyperbolic space with the Walrus graph visualisation tool and have developed a conversion tool that enables the conversion of standard phylogenetic tree formats to Walrus' format. With Walrus, it becomes possible to visualise and navigate phylogenetic trees with more than 100,000 nodes. Conclusion Walrus enables desktop visualisation of very large phylogenetic trees in 3 dimensional hyperbolic space. This application is potentially useful for visualisation of the tree of life and for functional genomics derivatives, like The Adaptive Evolution Database (TAED.

Climate-driven extinctions shape the phylogenetic structure of temperate tree floras.

Science.gov (United States)

Eiserhardt, Wolf L; Borchsenius, Finn; Plum, Christoffer M; Ordonez, Alejandro; Svenning, Jens-Christian

2015-03-01

When taxa go extinct, unique evolutionary history is lost. If extinction is selective, and the intrinsic vulnerabilities of taxa show phylogenetic signal, more evolutionary history may be lost than expected under random extinction. Under what conditions this occurs is insufficiently known. We show that late Cenozoic climate change induced phylogenetically selective regional extinction of northern temperate trees because of phylogenetic signal in cold tolerance, leading to significantly and substantially larger than random losses of phylogenetic diversity (PD). The surviving floras in regions that experienced stronger extinction are phylogenetically more clustered, indicating that non-random losses of PD are of increasing concern with increasing extinction severity. Using simulations, we show that a simple threshold model of survival given a physiological trait with phylogenetic signal reproduces our findings. Our results send a strong warning that we may expect future assemblages to be phylogenetically and possibly functionally depauperate if anthropogenic climate change affects taxa similarly. © 2015 John Wiley & Sons Ltd/CNRS.

Increased phylogenetic resolution using target enrichment in Rubus

Science.gov (United States)

Phylogenetic analyses in Rubus L. have been challenging due to polyploidy, hybridization, and apomixis within the genus. Wide morphological diversity occurs within and between species, contributing to challenges at lower and higher systematic levels. Phylogenetic inferences to date have been based o...

Phylogenetic relationships of African sunbird-like warblers: Moho ...

African Journals Online (AJOL)

Phylogenetic relationships of African sunbird-like warblers: Moho ( Hypergerus atriceps ), Green Hylia ( Hylia prasina ) and Tit-hylia ( Pholidornis rushiae ) ... different points in avian evolution reduces the phylogenetic signal in molecular sequence data, making difficult the reconstruction of relationships among taxa resulting ...

A new compound heterozygous CFTR mutation in a Chinese family with cystic fibrosis.

Science.gov (United States)

Xie, Yingjun; Huang, Xueqiong; Liang, Yujian; Xu, Lingling; Pei, Yuxin; Cheng, Yucai; Zhang, Lidan; Tang, Wen

2017-11-01

Cystic fibrosis (CF) is the most common autosomal recessive disease among Caucasians but is rarer in the Chinese population, because mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. To elucidate the causative role of a novel compound heterozygous mutation of CF. In this study, clinical samples were obtained from two siblings with recurrent airway infections, clubbed fingers, salt-sweat and failure to gain weight in a non-consanguineous Chinese family. Next-generation sequencing was performed on the 27 coding exons of CFTR in both children, with confirmation by Sanger sequencing. Next-generation sequencing showed the same compound heterozygous CFTR mutation (c.865A>T p.Arg289X and c.3651_3652insAAAT p.Tyr1219X) in both children. As this mutation is consistent with the clinical manifestations of CF and no other mutations were detected after scanning the gene sequence, we suggest that the CF phenotype is caused by compound heterozygosity for c.865A>T and c.3651_3652insAAAT. As c865A>T is not currently listed in the "Cystic Fibrosis Mutation Database", this information about CF in a Chinese population is of interest. © 2015 John Wiley & Sons Ltd.

Prospects for cellular mutational assays in human populations

International Nuclear Information System (INIS)

Mendelsohn, M.L.

1985-01-01

Practical, sensitive, effective, human cellular assays for detecting somatic and germinal mutations would have great value in environmental mutagenesis and carcinogenesis. When available, such assays should allow us to fill the void between human mutagenicity and the data that exist from short-term tests and from mutagenicity in other species. We will be able to validate the role of somatic mutations in carcinogenesis, to identify environmental factors that affect human germ cells, to integrate the effects of complex mixtures and the environment in the human subject, and to identify people who are hypersusceptible to genetic injury. Human cellular mutational assays, particularly when combined with cytogenetic and heritable mutational tests, promise to play pivotal roles in estimating the risk from low-dose radiation and chemical exposures. These combined methods avoid extrapolations of dose and from species to species, and may be sensitive enough and credible enough to permit politically, socially and scientifically acceptable risk management. 16 references

Utilization of complete chloroplast genomes for phylogenetic studies

NARCIS (Netherlands)

Ramlee, Shairul Izan Binti

2016-01-01

Chloroplast DNA sequence polymorphisms are a primary source of data in many plant phylogenetic studies. The chloroplast genome is relatively conserved in its evolution making it an ideal molecule to retain phylogenetic signals. The chloroplast genome is also largely, but not completely, free from

Phylogenetic reconstruction and shell evolution of the Diplommatinidae (Gastropoda: Caenogastropoda).

Science.gov (United States)

Webster, Nicole B; Van Dooren, Tom J M; Schilthuizen, Menno

2012-06-01

The fascinating and often unlikely shell shapes in the terrestrial micromollusc family Diplommatinidae (Gastropoda: Caenogastropoda) provide a particularly attractive set of multiple morphological traits to investigate evolutionary patterns of shape variation. Here, a molecular phylogenetic reconstruction, based on five genes and 2700 bp, was undertaken for this family, integrated with ancestral state reconstruction and phylogenetic PCA of discrete and quantitative traits, respectively. We found strong support for the Diplommatininae as a monophyletic group, separating the Cochlostomatidae into a separate family. Five main clades appear within the Diplommatininae, corresponding with both coiling direction and biogeographic patterns. A Belau clade (A) with highly diverse (but always sinistral) morphology comprised Hungerfordia, Palaina, and some Diplommatina. Arinia (dextral) and Opisthostoma (sinistroid) are sister groups in clade B. Clade C and D solely contain sinistral Diplommatina that are robust and little ornamented (clade C) or slender and sculptured (clade D). Clade E is dextral but biogeographically diverse with species from all sampled regions save the Caroline Islands. Adelopoma, Diplommatina, Palaina, and Hungerfordia require revision to allow taxonomy to reflect phylogeny, whereas Opisthostoma is clearly monophyletic. Ancestral state reconstruction suggests a sinistral origin for the Diplommatinidae, with three reversals to dextrality. Copyright © 2012 Elsevier Inc. All rights reserved.

Somatic mutations affect key pathways in lung adenocarcinoma

Science.gov (United States)

Ding, Li; Getz, Gad; Wheeler, David A.; Mardis, Elaine R.; McLellan, Michael D.; Cibulskis, Kristian; Sougnez, Carrie; Greulich, Heidi; Muzny, Donna M.; Morgan, Margaret B.; Fulton, Lucinda; Fulton, Robert S.; Zhang, Qunyuan; Wendl, Michael C.; Lawrence, Michael S.; Larson, David E.; Chen, Ken; Dooling, David J.; Sabo, Aniko; Hawes, Alicia C.; Shen, Hua; Jhangiani, Shalini N.; Lewis, Lora R.; Hall, Otis; Zhu, Yiming; Mathew, Tittu; Ren, Yanru; Yao, Jiqiang; Scherer, Steven E.; Clerc, Kerstin; Metcalf, Ginger A.; Ng, Brian; Milosavljevic, Aleksandar; Gonzalez-Garay, Manuel L.; Osborne, John R.; Meyer, Rick; Shi, Xiaoqi; Tang, Yuzhu; Koboldt, Daniel C.; Lin, Ling; Abbott, Rachel; Miner, Tracie L.; Pohl, Craig; Fewell, Ginger; Haipek, Carrie; Schmidt, Heather; Dunford-Shore, Brian H.; Kraja, Aldi; Crosby, Seth D.; Sawyer, Christopher S.; Vickery, Tammi; Sander, Sacha; Robinson, Jody; Winckler, Wendy; Baldwin, Jennifer; Chirieac, Lucian R.; Dutt, Amit; Fennell, Tim; Hanna, Megan; Johnson, Bruce E.; Onofrio, Robert C.; Thomas, Roman K.; Tonon, Giovanni; Weir, Barbara A.; Zhao, Xiaojun; Ziaugra, Liuda; Zody, Michael C.; Giordano, Thomas; Orringer, Mark B.; Roth, Jack A.; Spitz, Margaret R.; Wistuba, Ignacio I.; Ozenberger, Bradley; Good, Peter J.; Chang, Andrew C.; Beer, David G.; Watson, Mark A.; Ladanyi, Marc; Broderick, Stephen; Yoshizawa, Akihiko; Travis, William D.; Pao, William; Province, Michael A.; Weinstock, George M.; Varmus, Harold E.; Gabriel, Stacey B.; Lander, Eric S.; Gibbs, Richard A.; Meyerson, Matthew; Wilson, Richard K.

2009-01-01

Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers—including NF1, APC, RB1 and ATM—and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment. PMID:18948947

Estimating phylogenetic trees from genome-scale data.

Science.gov (United States)

Liu, Liang; Xi, Zhenxiang; Wu, Shaoyuan; Davis, Charles C; Edwards, Scott V

2015-12-01

The heterogeneity of signals in the genomes of diverse organisms poses challenges for traditional phylogenetic analysis. Phylogenetic methods known as "species tree" methods have been proposed to directly address one important source of gene tree heterogeneity, namely the incomplete lineage sorting that occurs when evolving lineages radiate rapidly, resulting in a diversity of gene trees from a single underlying species tree. Here we review theory and empirical examples that help clarify conflicts between species tree and concatenation methods, and misconceptions in the literature about the performance of species tree methods. Considering concatenation as a special case of the multispecies coalescent model helps explain differences in the behavior of the two methods on phylogenomic data sets. Recent work suggests that species tree methods are more robust than concatenation approaches to some of the classic challenges of phylogenetic analysis, including rapidly evolving sites in DNA sequences and long-branch attraction. We show that approaches, such as binning, designed to augment the signal in species tree analyses can distort the distribution of gene trees and are inconsistent. Computationally efficient species tree methods incorporating biological realism are a key to phylogenetic analysis of whole-genome data. © 2015 New York Academy of Sciences.

New weighting methods for phylogenetic tree reconstruction using multiple loci.

Science.gov (United States)

Misawa, Kazuharu; Tajima, Fumio

2012-08-01

Efficient determination of evolutionary distances is important for the correct reconstruction of phylogenetic trees. The performance of the pooled distance required for reconstructing a phylogenetic tree can be improved by applying large weights to appropriate distances for reconstructing phylogenetic trees and small weights to inappropriate distances. We developed two weighting methods, the modified Tajima-Takezaki method and the modified least-squares method, for reconstructing phylogenetic trees from multiple loci. By computer simulations, we found that both of the new methods were more efficient in reconstructing correct topologies than the no-weight method. Hence, we reconstructed hominoid phylogenetic trees from mitochondrial DNA using our new methods, and found that the levels of bootstrap support were significantly increased by the modified Tajima-Takezaki and by the modified least-squares method.

Quantification of sequence exchange events between PMS2 and PMS2CL provides a basis for improved mutation scanning of Lynch syndrome patients.

NARCIS (Netherlands)

Klift, H.M. van der; Tops, C.M.; Bik, E.C.; Boogaard, M.W.; Borgstein, A.M.; Hansson, K.B.; Ausems, M.G.E.M.; Gomez Garcia, E.; Green, A.; Hes, F.J.; Izatt, L.; Hest, L.P. van; Alonso, A.M.; Vriends, A.H.; Wagner, A.; Zelst-Stams, W.A.G. van; Vasen, H.F.; Morreau, H.; Devilee, P.; Wijnen, J.T.

2010-01-01

Heterozygous mutations in PMS2 are involved in Lynch syndrome, whereas biallelic mutations are found in Constitutional mismatch repair-deficiency syndrome patients. Mutation detection is complicated by the occurrence of sequence exchange events between the duplicated regions of PMS2 and PMS2CL. We

Diffusion tensor imaging of brain white matter in Huntington gene mutation individuals

Directory of Open Access Journals (Sweden)

Roberta Arb Saba

Full Text Available ABSTRACT Objective To evaluate the role of the involvement of white matter tracts in huntingtin gene mutation patients as a potential biomarker of the progression of the disease. Methods We evaluated 34 participants (11 symptomatic huntingtin gene mutation, 12 presymptomatic huntingtin gene mutation, and 11 controls. We performed brain magnetic resonance imaging to assess white matter integrity using diffusion tensor imaging, with measurement of fractional anisotropy. Results We observed a significant decrease of fractional anisotropy in the cortical spinal tracts, corona radiate, corpus callosum, external capsule, thalamic radiations, superior and inferior longitudinal fasciculus, and inferior frontal-occipital fasciculus in the Huntington disease group compared to the control and presymptomatic groups. Reduction of fractional anisotropy is indicative of a degenerative process and axonal loss. There was no statistically significant difference between the presymptomatic and control groups. Conclusion White matter integrity is affected in huntingtin gene mutation symptomatic individuals, but other studies with larger samples are required to assess its usefulness in the progression of the neurodegenerative process.

Electron Beam Scanning in Industrial Applications

Science.gov (United States)

Jongen, Yves; Herer, Arnold

1996-05-01

Scanned electron beams are used within many industries for applications such as sterilization of medical disposables, crosslinking of wire and cables insulating jackets, polymerization and degradation of resins and biomaterials, modification of semiconductors, coloration of gemstones and glasses, removal of oxides from coal plant flue gasses, and the curing of advanced composites and other molded forms. X-rays generated from scanned electron beams make yet other applications, such as food irradiation, viable. Typical accelerators for these applications range in beam energy from 0.5MeV to 10 MeV, with beam powers between 5 to 500kW and scanning widths between 20 and 300 cm. Since precise control of dose delivery is required in many of these applications, the integration of beam characteristics, product conveyance, and beam scanning mechanisms must be well understood and optimized. Fundamental issues and some case examples are presented.

Mutations in Membrin/GOSR2 Reveal Stringent Secretory Pathway Demands of Dendritic Growth and Synaptic Integrity

Directory of Open Access Journals (Sweden)

Roman Praschberger

2017-10-01

Full Text Available Mutations in the Golgi SNARE (SNAP [soluble NSF attachment protein] receptor protein Membrin (encoded by the GOSR2 gene cause progressive myoclonus epilepsy (PME. Membrin is a ubiquitous and essential protein mediating ER-to-Golgi membrane fusion. Thus, it is unclear how mutations in Membrin result in a disorder restricted to the nervous system. Here, we use a multi-layered strategy to elucidate the consequences of Membrin mutations from protein to neuron. We show that the pathogenic mutations cause partial reductions in SNARE-mediated membrane fusion. Importantly, these alterations were sufficient to profoundly impair dendritic growth in Drosophila models of GOSR2-PME. Furthermore, we show that Membrin mutations cause fragmentation of the presynaptic cytoskeleton coupled with transsynaptic instability and hyperactive neurotransmission. Our study highlights how dendritic growth is vulnerable even to subtle secretory pathway deficits, uncovers a role for Membrin in synaptic function, and provides a comprehensive explanatory basis for genotype-phenotype relationships in GOSR2-PME.

On the information content of discrete phylogenetic characters.

Science.gov (United States)

Bordewich, Magnus; Deutschmann, Ina Maria; Fischer, Mareike; Kasbohm, Elisa; Semple, Charles; Steel, Mike

2017-12-16

Phylogenetic inference aims to reconstruct the evolutionary relationships of different species based on genetic (or other) data. Discrete characters are a particular type of data, which contain information on how the species should be grouped together. However, it has long been known that some characters contain more information than others. For instance, a character that assigns the same state to each species groups all of them together and so provides no insight into the relationships of the species considered. At the other extreme, a character that assigns a different state to each species also conveys no phylogenetic signal. In this manuscript, we study a natural combinatorial measure of the information content of an individual character and analyse properties of characters that provide the maximum phylogenetic information, particularly, the number of states such a character uses and how the different states have to be distributed among the species or taxa of the phylogenetic tree.

DendroPy: a Python library for phylogenetic computing.

Science.gov (United States)

Sukumaran, Jeet; Holder, Mark T

2010-06-15

DendroPy is a cross-platform library for the Python programming language that provides for object-oriented reading, writing, simulation and manipulation of phylogenetic data, with an emphasis on phylogenetic tree operations. DendroPy uses a splits-hash mapping to perform rapid calculations of tree distances, similarities and shape under various metrics. It contains rich simulation routines to generate trees under a number of different phylogenetic and coalescent models. DendroPy's data simulation and manipulation facilities, in conjunction with its support of a broad range of phylogenetic data formats (NEXUS, Newick, PHYLIP, FASTA, NeXML, etc.), allow it to serve a useful role in various phyloinformatics and phylogeographic pipelines. The stable release of the library is available for download and automated installation through the Python Package Index site (http://pypi.python.org/pypi/DendroPy), while the active development source code repository is available to the public from GitHub (http://github.com/jeetsukumaran/DendroPy).

On the quirks of maximum parsimony and likelihood on phylogenetic networks.

Science.gov (United States)

Bryant, Christopher; Fischer, Mareike; Linz, Simone; Semple, Charles

2017-03-21

Maximum parsimony is one of the most frequently-discussed tree reconstruction methods in phylogenetic estimation. However, in recent years it has become more and more apparent that phylogenetic trees are often not sufficient to describe evolution accurately. For instance, processes like hybridization or lateral gene transfer that are commonplace in many groups of organisms and result in mosaic patterns of relationships cannot be represented by a single phylogenetic tree. This is why phylogenetic networks, which can display such events, are becoming of more and more interest in phylogenetic research. It is therefore necessary to extend concepts like maximum parsimony from phylogenetic trees to networks. Several suggestions for possible extensions can be found in recent literature, for instance the softwired and the hardwired parsimony concepts. In this paper, we analyze the so-called big parsimony problem under these two concepts, i.e. we investigate maximum parsimonious networks and analyze their properties. In particular, we show that finding a softwired maximum parsimony network is possible in polynomial time. We also show that the set of maximum parsimony networks for the hardwired definition always contains at least one phylogenetic tree. Lastly, we investigate some parallels of parsimony to different likelihood concepts on phylogenetic networks. Copyright © 2017 Elsevier Ltd. All rights reserved.

Systematic Analysis of Splice-Site-Creating Mutations in Cancer.

Science.gov (United States)

Jayasinghe, Reyka G; Cao, Song; Gao, Qingsong; Wendl, Michael C; Vo, Nam Sy; Reynolds, Sheila M; Zhao, Yanyan; Climente-González, Héctor; Chai, Shengjie; Wang, Fang; Varghese, Rajees; Huang, Mo; Liang, Wen-Wei; Wyczalkowski, Matthew A; Sengupta, Sohini; Li, Zhi; Payne, Samuel H; Fenyö, David; Miner, Jeffrey H; Walter, Matthew J; Vincent, Benjamin; Eyras, Eduardo; Chen, Ken; Shmulevich, Ilya; Chen, Feng; Ding, Li

2018-04-03

For the past decade, cancer genomic studies have focused on mutations leading to splice-site disruption, overlooking those having splice-creating potential. Here, we applied a bioinformatic tool, MiSplice, for the large-scale discovery of splice-site-creating mutations (SCMs) across 8,656 TCGA tumors. We report 1,964 originally mis-annotated mutations having clear evidence of creating alternative splice junctions. TP53 and GATA3 have 26 and 18 SCMs, respectively, and ATRX has 5 from lower-grade gliomas. Mutations in 11 genes, including PARP1, BRCA1, and BAP1, were experimentally validated for splice-site-creating function. Notably, we found that neoantigens induced by SCMs are likely several folds more immunogenic compared to missense mutations, exemplified by the recurrent GATA3 SCM. Further, high expression of PD-1 and PD-L1 was observed in tumors with SCMs, suggesting candidates for immune blockade therapy. Our work highlights the importance of integrating DNA and RNA data for understanding the functional and the clinical implications of mutations in human diseases. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Niche conservatism and phylogenetic clustering in a tribe of arid-adapted marsupial mice, the Sminthopsini.

Science.gov (United States)

García-Navas, Vicente; Westerman, Michael

2018-05-28

The progressive expansion of the Australian arid zone during the last 20 Ma appears to have spurred the diversification of several families of plants, vertebrates and invertebrates, yet such taxonomic groups appear to show limited niche radiation. Here, we test whether speciation is associated with niche conservatism (constraints on ecological divergence) or niche divergence in a tribe of marsupial mice (Sminthopsini; 23 taxa) that includes the most speciose genus of living dasyurids, the sminthopsins. To that end, we integrated phylogenetic data with ecological niche modelling, to enable us to reconstruct the evolution of climatic suitability within Sminthopsini. Niche overlap among species was low-moderate (but generally higher than expected given environmental background similarity), and the degree of phylogenetic clustering increased with aridity. Climatic niche reconstruction illustrates that there has been little apparent evolution of climatic tolerance within clades. Accordingly, climatic disparity tends to be accumulated among clades, suggesting considerable niche conservatism. Our results also indicate that evolution of climatic tolerances has been heterogeneous across different dimensions of climate (temperature vs. precipitation) and across phylogenetic clusters (Sminthopsis murina group vs. other groups). Although some results point to the existence of shifts in climatic niches during the speciation of sminthopsins, our study provides evidence for substantial phylogenetic niche conservatism in the group. We conclude that niche diversification had a low impact on the speciation of this tribe of small, but highly mobile marsupials. © 2018 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2018 European Society For Evolutionary Biology.

Community Phylogenetics: Assessing Tree Reconstruction Methods and the Utility of DNA Barcodes

Science.gov (United States)

Boyle, Elizabeth E.; Adamowicz, Sarah J.

2015-01-01

Studies examining phylogenetic community structure have become increasingly prevalent, yet little attention has been given to the influence of the input phylogeny on metrics that describe phylogenetic patterns of co-occurrence. Here, we examine the influence of branch length, tree reconstruction method, and amount of sequence data on measures of phylogenetic community structure, as well as the phylogenetic signal (Pagel’s λ) in morphological traits, using Trichoptera larval communities from Churchill, Manitoba, Canada. We find that model-based tree reconstruction methods and the use of a backbone family-level phylogeny improve estimations of phylogenetic community structure. In addition, trees built using the barcode region of cytochrome c oxidase subunit I (COI) alone accurately predict metrics of phylogenetic community structure obtained from a multi-gene phylogeny. Input tree did not alter overall conclusions drawn for phylogenetic signal, as significant phylogenetic structure was detected in two body size traits across input trees. As the discipline of community phylogenetics continues to expand, it is important to investigate the best approaches to accurately estimate patterns. Our results suggest that emerging large datasets of DNA barcode sequences provide a vast resource for studying the structure of biological communities. PMID:26110886

Subacute Budd-Chiari syndrome associated with polycythemia vera and factor V Leiden mutation

NARCIS (Netherlands)

Simsek, S; Verheesen, RV; Haagsma, EB; Lourens, J

We describe a 48-year-old caucasian woman with a subacute Budd-Chiari syndrome attributed to the presence of polycythaemia vera, heterozygosity for the factor V Leiden mutation and the use of an oral contraceptive pill. Two diagnostic pitfalls were encountered. First, on CT scanning of the abdomen

Consequences of recombination on traditional phylogenetic analysis

DEFF Research Database (Denmark)

Schierup, M H; Hein, J

2000-01-01

We investigate the shape of a phylogenetic tree reconstructed from sequences evolving under the coalescent with recombination. The motivation is that evolutionary inferences are often made from phylogenetic trees reconstructed from population data even though recombination may well occur (mt......DNA or viral sequences) or does occur (nuclear sequences). We investigate the size and direction of biases when a single tree is reconstructed ignoring recombination. Standard software (PHYLIP) was used to construct the best phylogenetic tree from sequences simulated under the coalescent with recombination....... With recombination present, the length of terminal branches and the total branch length are larger, and the time to the most recent common ancestor smaller, than for a tree reconstructed from sequences evolving with no recombination. The effects are pronounced even for small levels of recombination that may...

Phylogenetic relationships of the lancelets of the genus ...

African Journals Online (AJOL)

phylogenetic relationships of the Branchiostoma lancelets from South (Xiamen) and North (Qingdao and Rizhao) China, and phylogenetic trees constructed also included the existing data from Japanese waters. The genetic distances of the lancelets between South and North China averaged 0.19, 0.21, and 0.17 based on ...

Induced mutations and marker assisted breeding in soybean

Energy Technology Data Exchange (ETDEWEB)

Chotechuen, Somsong [Prachinburi Rice Research Center, Prachinburi (Thailand); Srisombun, Somsak [Department of Agriculture, Field Crops Research Institute, Bangkok (Thailand); Lamseejan, Siranut [Kasetsart Univ., Department of Applied Radiation and Isotopes, Bangkok (Thailand)

2002-02-01

Soybean is one of the important crops in Thailand. Constraints to soybean production include low yield potential, susceptibility to diseases and insects, and non-adoption of appropriate management practices. Mutation induction has been used to improve soybean yield and resistance to major diseases such as rust, purple seed, crinkle leaf, anthracnose and green seed. This paper reviews previous work and achievements of induced mutations in soybean. Successful examples are the release of a soybean variety, Doi Kham, and the development of a mutant CM 60-10kr-71; both are resistant to rust disease. The paper also gives example of the use of soybean SSR markers to identify QTL associated with pod shattering, and emphasizes the integration of mutation techniques and marker assisted selection for soybean improvement. (author)

Enumerating all maximal frequent subtrees in collections of phylogenetic trees.

Science.gov (United States)

Deepak, Akshay; Fernández-Baca, David

2014-01-01

A common problem in phylogenetic analysis is to identify frequent patterns in a collection of phylogenetic trees. The goal is, roughly, to find a subset of the species (taxa) on which all or some significant subset of the trees agree. One popular method to do so is through maximum agreement subtrees (MASTs). MASTs are also used, among other things, as a metric for comparing phylogenetic trees, computing congruence indices and to identify horizontal gene transfer events. We give algorithms and experimental results for two approaches to identify common patterns in a collection of phylogenetic trees, one based on agreement subtrees, called maximal agreement subtrees, the other on frequent subtrees, called maximal frequent subtrees. These approaches can return subtrees on larger sets of taxa than MASTs, and can reveal new common phylogenetic relationships not present in either MASTs or the majority rule tree (a popular consensus method). Our current implementation is available on the web at https://code.google.com/p/mfst-miner/. Our computational results confirm that maximal agreement subtrees and all maximal frequent subtrees can reveal a more complete phylogenetic picture of the common patterns in collections of phylogenetic trees than maximum agreement subtrees; they are also often more resolved than the majority rule tree. Further, our experiments show that enumerating maximal frequent subtrees is considerably more practical than enumerating ordinary (not necessarily maximal) frequent subtrees.

Computer graphic display of cardiac CT scans

International Nuclear Information System (INIS)

Palmer, R.; Carlsson, E.

1982-01-01

In order to improve spatial conception and quantitative assessment of the cardiac structures based on cardiac computed tomography, methods for computer graphic display were developed. Excised hearts and living dogs with myocardial infarctions were subjected to CT scanning. The data on the scanner tapes were processed to provide isodensity plots, linear section plots, time-weighted integrated isodensity plots as well as topographical density displays and three-dimensional spatial reconstructions of single and multi-layer scans. (orig.)

A novel nonsense mutation in the tyrosinase gene is related to the albinism in a capuchin monkey (Sapajus apella).

Science.gov (United States)

Galante Rocha de Vasconcelos, Felipe Tadeu; Hauzman, Einat; Dutra Henriques, Leonardo; Kilpp Goulart, Paulo Roney; de Faria Galvão, Olavo; Sano, Ronaldo Yuiti; da Silva Souza, Givago; Lynch Alfaro, Jessica; de Lima Silveira, Luis Carlos; Fix Ventura, Dora; Oliveira Bonci, Daniela Maria

2017-05-05

Oculocutaneous Albinism (OCA) is an autosomal recessive inherited condition that affects the pigmentation of eyes, hair and skin. The OCA phenotype may be caused by mutations in the tyrosinase gene (TYR), which expresses the tyrosinase enzyme and has an important role in the synthesis of melanin pigment. The aim of this study was to identify the genetic mutation responsible for the albinism in a captive capuchin monkey, and to describe the TYR gene of normal phenotype individuals. In addition, we identified the subject's species. A homozygous nonsense mutation was identified in exon 1 of the TYR gene, with the substitution of a cytosine for a thymine nucleotide (C64T) at codon 22, leading to a premature stop codon (R22X) in the albino robust capuchin monkey. The albino and five non-albino robust capuchin monkeys were identified as Sapajus apella, based on phylogenetic analyses, pelage pattern and geographic provenance. One individual was identified as S. macrocephalus. We conclude that the point mutation C64T in the TYR gene is responsible for the OCA1 albino phenotype in the capuchin monkey, classified as Sapajus apella.

Phylogenetic analysis of ferlin genes reveals ancient eukaryotic origins

Directory of Open Access Journals (Sweden)

Lek Monkol

2010-07-01

Full Text Available Abstract Background The ferlin gene family possesses a rare and identifying feature consisting of multiple tandem C2 domains and a C-terminal transmembrane domain. Much currently remains unknown about the fundamental function of this gene family, however, mutations in its two most well-characterised members, dysferlin and otoferlin, have been implicated in human disease. The availability of genome sequences from a wide range of species makes it possible to explore the evolution of the ferlin family, providing contextual insight into characteristic features that define the ferlin gene family in its present form in humans. Results Ferlin genes were detected from all species of representative phyla, with two ferlin subgroups partitioned within the ferlin phylogenetic tree based on the presence or absence of a DysF domain. Invertebrates generally possessed two ferlin genes (one with DysF and one without, with six ferlin genes in most vertebrates (three DysF, three non-DysF. Expansion of the ferlin gene family is evident between the divergence of lamprey (jawless vertebrates and shark (cartilaginous fish. Common to almost all ferlins is an N-terminal C2-FerI-C2 sandwich, a FerB motif, and two C-terminal C2 domains (C2E and C2F adjacent to the transmembrane domain. Preservation of these structural elements throughout eukaryotic evolution suggests a fundamental role of these motifs for ferlin function. In contrast, DysF, C2DE, and FerA are optional, giving rise to subtle differences in domain topologies of ferlin genes. Despite conservation of multiple C2 domains in all ferlins, the C-terminal C2 domains (C2E and C2F displayed higher sequence conservation and greater conservation of putative calcium binding residues across paralogs and orthologs. Interestingly, the two most studied non-mammalian ferlins (Fer-1 and Misfire in model organisms C. elegans and D. melanogaster, present as outgroups in the phylogenetic analysis, with results suggesting

Comparative phylogenetic analysis of intergenic spacers and small ...

African Journals Online (AJOL)

The phylogenetic analysis of test isolates included assessment of variation in sequences and length of IGS and SSU-rRNA genes with reference to 16 different microsporidian sequences. The results proved that IGS sequences have more variation than SSU-rRNA gene sequences. Analysis of phylogenetic trees reveal that ...

Phylogenetic comparative methods complement discriminant function analysis in ecomorphology.

Science.gov (United States)

Barr, W Andrew; Scott, Robert S

2014-04-01

In ecomorphology, Discriminant Function Analysis (DFA) has been used as evidence for the presence of functional links between morphometric variables and ecological categories. Here we conduct simulations of characters containing phylogenetic signal to explore the performance of DFA under a variety of conditions. Characters were simulated using a phylogeny of extant antelope species from known habitats. Characters were modeled with no biomechanical relationship to the habitat category; the only sources of variation were body mass, phylogenetic signal, or random "noise." DFA on the discriminability of habitat categories was performed using subsets of the simulated characters, and Phylogenetic Generalized Least Squares (PGLS) was performed for each character. Analyses were repeated with randomized habitat assignments. When simulated characters lacked phylogenetic signal and/or habitat assignments were random, ecomorphology. Copyright © 2013 Wiley Periodicals, Inc.

Maximum Parsimony on Phylogenetic networks

Science.gov (United States)

2012-01-01

Background Phylogenetic networks are generalizations of phylogenetic trees, that are used to model evolutionary events in various contexts. Several different methods and criteria have been introduced for reconstructing phylogenetic trees. Maximum Parsimony is a character-based approach that infers a phylogenetic tree by minimizing the total number of evolutionary steps required to explain a given set of data assigned on the leaves. Exact solutions for optimizing parsimony scores on phylogenetic trees have been introduced in the past. Results In this paper, we define the parsimony score on networks as the sum of the substitution costs along all the edges of the network; and show that certain well-known algorithms that calculate the optimum parsimony score on trees, such as Sankoff and Fitch algorithms extend naturally for networks, barring conflicting assignments at the reticulate vertices. We provide heuristics for finding the optimum parsimony scores on networks. Our algorithms can be applied for any cost matrix that may contain unequal substitution costs of transforming between different characters along different edges of the network. We analyzed this for experimental data on 10 leaves or fewer with at most 2 reticulations and found that for almost all networks, the bounds returned by the heuristics matched with the exhaustively determined optimum parsimony scores. Conclusion The parsimony score we define here does not directly reflect the cost of the best tree in the network that displays the evolution of the character. However, when searching for the most parsimonious network that describes a collection of characters, it becomes necessary to add additional cost considerations to prefer simpler structures, such as trees over networks. The parsimony score on a network that we describe here takes into account the substitution costs along the additional edges incident on each reticulate vertex, in addition to the substitution costs along the other edges which are

Maximum parsimony, substitution model, and probability phylogenetic trees.

Science.gov (United States)

Weng, J F; Thomas, D A; Mareels, I

2011-01-01

The problem of inferring phylogenies (phylogenetic trees) is one of the main problems in computational biology. There are three main methods for inferring phylogenies-Maximum Parsimony (MP), Distance Matrix (DM) and Maximum Likelihood (ML), of which the MP method is the most well-studied and popular method. In the MP method the optimization criterion is the number of substitutions of the nucleotides computed by the differences in the investigated nucleotide sequences. However, the MP method is often criticized as it only counts the substitutions observable at the current time and all the unobservable substitutions that really occur in the evolutionary history are omitted. In order to take into account the unobservable substitutions, some substitution models have been established and they are now widely used in the DM and ML methods but these substitution models cannot be used within the classical MP method. Recently the authors proposed a probability representation model for phylogenetic trees and the reconstructed trees in this model are called probability phylogenetic trees. One of the advantages of the probability representation model is that it can include a substitution model to infer phylogenetic trees based on the MP principle. In this paper we explain how to use a substitution model in the reconstruction of probability phylogenetic trees and show the advantage of this approach with examples.

Linking world scan and image

International Nuclear Information System (INIS)

Timmer, H.; Alcamo, J.; Bollen, J.; Gielen, A.; Gerlach, R.; Den Ouden, A.; Zuidema, G.

1995-01-01

In march 1994 the Central Planning Bureau (CPB) in the Hague, the National Institute of Public Health and Environmental Protection (RIVM) in Bilthoven and the Institute of Environmental Studies (IES) in Amsterdam started the first phase of a joint research program aimed at creating integrated scenarios of the global economy, GHG emissions, and climate impacts. The goal of the first phase of this project was to design and test a linked version of the economic model WORLD SCAN of the former, and the climate model IMAGE 2 of the latter institute. This first phase has resulted in the planned test runs with an operational version of the linked models by May 1995. The experiences in the first year were encouraging, both in the scientific and the organizational sense. In a sense, a link was made between scientific disciplines: a coupling of disciplines concerning with global economic development and the global physical climate system is difficult and novel. The goal of the project was to integrate long-term economic developments and effects of climate change. Both the WORLD SCAN model and IMAGE 2 provide a consistent analysis of the global system, but from different perspectives. IMAGE 2 simulates climate change and its effects in a global context but treats the economic system as exogenous. WORLD SCAN covers the world economic system in a consistent manner but does not take into account the global environment. The links are constructed in the area of agriculture and energy. The basic idea is that WORLD SCAN determines demand and supply on economic principles, while IMAGE 2 provides information on changes of land area and average quality of productive land, and other damage costs based on its three sub-systems. The demand for energy is fed into IMAGE 2's Energy Industry subsystem (EIS), which in turn determines emissions of greenhouse gases. Furthermore, some additional output from WORLD SCAN on activity levels, prices and capital structure can be used to determine

Scanning probe microscopy competency development

Energy Technology Data Exchange (ETDEWEB)

Hawley, M.E.; Reagor, D.W.; Jia, Quan Xi [and others

1998-12-31

This is the final report of a three-year, Laboratory Directed Research and Development (LDRD) project at Los Alamos National Laboratory (LANL). The project collaborators developed an ultra-high vacuum scanning tunneling microscope (UHV-STM) capability, integrated it with existing scanning probe microscopes, and developed new, advanced air-based scanning force techniques (SPMs). Programmatic, basic, and industrially related laboratory research requires the existence of SPMs, as well as expertise capable of providing local nano-scale information. The UHV-STM capability, equipped with load-lock system and several surface science techniques, will allow introduction, examination, and reaction of surfaces prepared under well-controlled vacuum conditions, including the examination of morphology and local bonding associated with the initial stages of film growth under controlled growth conditions. The resulting capabilities will enable the authors to respond to a variety of problems requiring local characterization of conducting and nonconducting surfaces in liquids, air, and UHV.

Cone and Rod Loss in Stargardt Disease Revealed by Adaptive Optics Scanning Light Ophthalmoscopy

Science.gov (United States)

Song, Hongxin; Rossi, Ethan A.; Latchney, Lisa; Bessette, Angela; Stone, Edwin; Hunter, Jennifer J.; Williams, David R.; Chung, Mina

2015-01-01

Importance Stargardt disease (STGD1) is characterized by macular atrophy and flecks in the retinal pigment epithelium. The causative ABCA4 gene encodes a protein localizing to photoreceptor outer segments. The pathologic steps by which ABCA4 mutations lead to clinically detectable retinal pigment epithelium changes remain unclear. We investigated early STGD1 using adaptive optics scanning light ophthalmoscopy. Observations Adaptive optics scanning light ophthalmoscopy imaging of 2 brothers with early STGD1 and their unaffected parents was compared with conventional imaging. Cone and rod spacing were increased in both patients (P optics scanning light ophthalmoscopy reveals increased cone and rod spacing in areas that appear normal in conventional images, suggesting that photoreceptor loss precedes clinically detectable retinal pigment epithelial disease in STGD1. PMID:26247787

An efficient and extensible approach for compressing phylogenetic trees

KAUST Repository

Matthews, Suzanne J; Williams, Tiffani L

2011-01-01

Background: Biologists require new algorithms to efficiently compress and store their large collections of phylogenetic trees. Our previous work showed that TreeZip is a promising approach for compressing phylogenetic trees. In this paper, we extend

Fire modifies the phylogenetic structure of soil bacterial co-occurrence networks.

Science.gov (United States)

Pérez-Valera, Eduardo; Goberna, Marta; Faust, Karoline; Raes, Jeroen; García, Carlos; Verdú, Miguel

2017-01-01

Fire alters ecosystems by changing the composition and community structure of soil microbes. The phylogenetic structure of a community provides clues about its main assembling mechanisms. While environmental filtering tends to reduce the community phylogenetic diversity by selecting for functionally (and hence phylogenetically) similar species, processes like competitive exclusion by limiting similarity tend to increase it by preventing the coexistence of functionally (and phylogenetically) similar species. We used co-occurrence networks to detect co-presence (bacteria that co-occur) or exclusion (bacteria that do not co-occur) links indicative of the ecological interactions structuring the community. We propose that inspecting the phylogenetic structure of co-presence or exclusion links allows to detect the main processes simultaneously assembling the community. We monitored a soil bacterial community after an experimental fire and found that fire altered its composition, richness and phylogenetic diversity. Both co-presence and exclusion links were more phylogenetically related than expected by chance. We interpret such a phylogenetic clustering in co-presence links as a result of environmental filtering, while that in exclusion links reflects competitive exclusion by limiting similarity. This suggests that environmental filtering and limiting similarity operate simultaneously to assemble soil bacterial communities, widening the traditional view that only environmental filtering structures bacterial communities. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

Conus pennaceus : a phylogenetic analysis of the Mozambican ...

African Journals Online (AJOL)

The genus Conus has over 500 species and is the most species-rich taxon of marine invertebrates. Based on mitochondrial DNA, this study focuses on the phylogenetics of Conus, particularly the pennaceus complex collected along the Mozambican coast. Phylogenetic trees based on both the 16S and the 12S ribosomal ...

HIV-1 transmission patterns in antiretroviral therapy-naive, HIV-infected North Americans based on phylogenetic analysis by population level and ultra-deep DNA sequencing.

Directory of Open Access Journals (Sweden)

Lisa L Ross

Full Text Available Factors that contribute to the transmission of human immunodeficiency virus type 1 (HIV-1, especially drug-resistant HIV-1 variants remain a significant public health concern. In-depth phylogenetic analyses of viral sequences obtained in the screening phase from antiretroviral-naïve HIV-infected patients seeking enrollment in EPZ108859, a large open-label study in the USA, Canada and Puerto Rico (ClinicalTrials.gov NCT00440947 were examined for insights into the roles of drug resistance and epidemiological factors that could impact disease dissemination. Viral transmission clusters (VTCs were initially predicted from a phylogenetic analysis of population level HIV-1 pol sequences obtained from 690 antiretroviral-naïve subjects in 2007. Subsequently, the predicted VTCs were tested for robustness by ultra deep sequencing (UDS using pyrosequencing technology and further phylogenetic analyses. The demographic characteristics of clustered and non-clustered subjects were then compared. From 690 subjects, 69 were assigned to 1 of 30 VTCs, each containing 2 to 5 subjects. Race composition of VTCs were significantly more likely to be white (72% vs. 60%; p = 0.04. VTCs had fewer reverse transcriptase and major PI resistance mutations (9% vs. 24%; p = 0.002 than non-clustered sequences. Both men-who-have-sex-with-men (MSM (68% vs. 48%; p = 0.001 and Canadians (29% vs. 14%; p = 0.03 were significantly more frequent in VTCs than non-clustered sequences. Of the 515 subjects who initiated antiretroviral therapy, 33 experienced confirmed virologic failure through 144 weeks while only 3/33 were from VTCs. Fewer VTCs subjects (as compared to those with non-clustering virus had HIV-1 with resistance-associated mutations or experienced virologic failure during the course of the study. Our analysis shows specific geographical and drug resistance trends that correlate well with transmission clusters defined by HIV sequences of similarity

A novel missense HGD gene mutation, K57N, in a patient with alkaptonuria.

Science.gov (United States)

Grasko, Jonathan M; Hooper, Amanda J; Brown, Jeffrey W; McKnight, C James; Burnett, John R

2009-05-01

Alkaptonuria is a rare recessive disorder of phenylalanine/tyrosine metabolism due to a defect in the enzyme homogentisate 1,2-dioxygenase (HGD) caused by mutations in the HGD gene. We report the case of a 38 year-old male with known alkaptonuria who was referred to an adult metabolic clinic after initially presenting to an emergency department with renal colic and subsequently passing black ureteric calculi. He complained of severe debilitating lower back pain, worsening over the last few years. A CT scan revealed marked degenerative changes and severe narrowing of the disc spaces along the entire lumbar spine. Sequencing of the HGD gene revealed that he was a compound heterozygote for a previously described missense mutation in exon 13 (G360R) and a novel missense mutation in exon 3 (K57N). Lys(57) is conserved among species and mutation of this residue is predicted to affect HGD protein function by interfering with substrate traffic at the active site. In summary, we describe an alkaptonuric patient and report a novel missense HGD mutation, K57N.

Study on Chinese space mutation breeding by integrating the earth with the space

International Nuclear Information System (INIS)

Wen Xianfang; Zhang Long; Dai Weixu; Li Chunhua

2004-01-01

This paper described the status of space mutation breeding in China. It emphasized that since 1978 Chinese Space scientists and agricultural biologists have send 50 kg seeds of more than 70 crops including cereals, cotton, oil, vegetable, fruit and pasture to the space using the facilities such as reture satellite 9 times, Shenzhou aircraft twice and high balloon 4 times, and 19 new varieties with high yield, high quality and disease-resistance, including five rice varieties, two wheat varieties, two cotton varieties, one sweat pepper, one tomato variety, one sesame variety, three water melon varieties, one lotus varieties and one ganaderma lucidum variety, have been bred though years of breeding at the Earth at more than 70 Chinese research institutes in 22 provinces. In addition more than 50 new lines and many other germ plasma resources have been obtained. Study on space breeding mechanism, such as biological effect of space induction, genetic variation by cell and molecular techniques and simulated study at the earth, has been conducted and some progresses have been achieved. Many space-breeding bases have been established in some provinces. Space varieties have been extended up to 270000 hectares, and some useful scientific achievements and social economic benefit had been made. The study of Chinese space mutation breading is going ahead in the world. The paper also introduced the contribution and results made by former three reture satellites in space science. Some basic parameters listed involved in study on space mutation breeding and the former three reture satellites. We also prospected the future of space mutation breeding. (authors)

Trophic phylogenetics: evolutionary influences on body size, feeding, and species associations in grassland arthropods.

Science.gov (United States)

Lind, Eric M; Vincent, John B; Weiblen, George D; Cavender-Bares, Jeannine; Borer, Elizabeth T

2015-04-01

Contemporary animal-plant interactions such as herbivory are widely understood to be shaped by evolutionary history. Yet questions remain about the role of plant phylogenetic diversity in generating and maintaining herbivore diversity, and whether evolutionary relatedness of producers might predict the composition of consumer communities. We tested for evidence of evolutionary associations among arthropods and the plants on which they were found, using phylogenetic analysis of naturally occurring arthropod assemblages sampled from a plant-diversity manipulation experiment. Considering phylogenetic relationships among more than 900 arthropod consumer taxa and 29 plant species in the experiment, we addressed several interrelated questions. First, our results support the hypothesis that arthropod functional traits such as body size and trophic role are phylogenetically conserved in community ecological samples. Second, herbivores tended to cooccur with closer phylogenetic relatives than would be expected at random, whereas predators and parasitoids did not show phylogenetic association patterns. Consumer specialization, as measured by association through time with monocultures of particular host plant species, showed significant phylogenetic signal, although the. strength of this association varied among plant species. Polycultures of phylogenetically dissimilar plant species supported more phylogenetically dissimilar consumer communities than did phylogenetically similar polycultures. Finally, we separated the effects of plant species richness and relatedness in predicting the phylogenetic distribution of the arthropod assemblages in this experiment. The phylogenetic diversity of plant communities predicted the phylogenetic diversity of herbivore communities even after accounting for plant species richness. The phylogenetic diversity of secondary consumers differed by guild, with predator phylogenetic diversity responding to herbivore relatedness, while parasitoid

Enumerating all maximal frequent subtrees in collections of phylogenetic trees

Science.gov (United States)

2014-01-01

Background A common problem in phylogenetic analysis is to identify frequent patterns in a collection of phylogenetic trees. The goal is, roughly, to find a subset of the species (taxa) on which all or some significant subset of the trees agree. One popular method to do so is through maximum agreement subtrees (MASTs). MASTs are also used, among other things, as a metric for comparing phylogenetic trees, computing congruence indices and to identify horizontal gene transfer events. Results We give algorithms and experimental results for two approaches to identify common patterns in a collection of phylogenetic trees, one based on agreement subtrees, called maximal agreement subtrees, the other on frequent subtrees, called maximal frequent subtrees. These approaches can return subtrees on larger sets of taxa than MASTs, and can reveal new common phylogenetic relationships not present in either MASTs or the majority rule tree (a popular consensus method). Our current implementation is available on the web at https://code.google.com/p/mfst-miner/. Conclusions Our computational results confirm that maximal agreement subtrees and all maximal frequent subtrees can reveal a more complete phylogenetic picture of the common patterns in collections of phylogenetic trees than maximum agreement subtrees; they are also often more resolved than the majority rule tree. Further, our experiments show that enumerating maximal frequent subtrees is considerably more practical than enumerating ordinary (not necessarily maximal) frequent subtrees. PMID:25061474

Phylogenetic fields through time: temporal dynamics of geographical co-occurrence and phylogenetic structure within species ranges.

Science.gov (United States)

Villalobos, Fabricio; Carotenuto, Francesco; Raia, Pasquale; Diniz-Filho, José Alexandre F

2016-04-05

Species co-occur with different sets of other species across their geographical distribution, which can be either closely or distantly related. Such co-occurrence patterns and their phylogenetic structure within individual species ranges represent what we call the species phylogenetic fields (PFs). These PFs allow investigation of the role of historical processes--speciation, extinction and dispersal--in shaping species co-occurrence patterns, in both extinct and extant species. Here, we investigate PFs of large mammalian species during the last 3 Myr, and how these correlate with trends in diversification rates. Using the fossil record, we evaluate species' distributional and co-occurrence patterns along with their phylogenetic structure. We apply a novel Bayesian framework on fossil occurrences to estimate diversification rates through time. Our findings highlight the effect of evolutionary processes and past climatic changes on species' distributions and co-occurrences. From the Late Pliocene to the Recent, mammal species seem to have responded in an individualistic manner to climate changes and diversification dynamics, co-occurring with different sets of species from different lineages across their geographical ranges. These findings stress the difficulty of forecasting potential effects of future climate changes on biodiversity. © 2016 The Author(s).

Phylogenetic Analysis of Canine Parvovirus VP2 Gene in China.

Science.gov (United States)

Yi, L; Tong, M; Cheng, Y; Song, W; Cheng, S

2016-04-01

In this study, a total of 37 samples (58.0%) were found through PCR assay to be positive for canine parvovirus (CPV) of 66 suspected faecal samples of dogs collected from various cities throughout China. Eight CPV isolates could be obtained in the CRFK cell line. The sequencing of the VP2 gene of CPV identified the predominant CPV strain as CPV-2a (Ser297Ala), with two CPV-2b (Ser297Ala). Sequence comparison revealed homologies of 99.3-99.9%, 99.9% and 99.3-99.7% within the CPV 2a isolates, within the CPV 2b isolates and between the CPV 2a and 2b isolates, respectively. In addition, several non-synonymous and synonymous mutations were also recorded. The phylogenetic tree revealed that most of the CPV strains from different areas in China were located in the formation of a large branch, which were grouped together along with the KU143-09 strain from Thailand and followed the same evolution. In this study, we provide an updated molecular characterization of CPV 2 circulation in China. © 2014 Blackwell Verlag GmbH.

R and D activities on radiation induced mutation breeding

International Nuclear Information System (INIS)

Lapade, A.G.; Asencion, A.B.; Santos, I.S.; Grafia, A.O.; Veluz, AM.S.; Barrida, A.C.; Marbella, L.J.

1996-01-01

This paper summarizes the accomplishments, prospects and future plans of mutation breeding for crop improvement at the Philippine Nuclear Research Institute (PNRI). Mutation induction has become a proven way creating variation within a crop variety and inducing desired attributes that cannot be found in nature or have been lost during evolution. Several improved varieties with desirable traits were successfully developed through induced mutation breeding at our research institute. In rice, mutation breeding has resulted in the development of new varieties: (1) PARC 2, (2) Milagrosa mutant, (3) Bengawan mutant and (4) Azmil mutant. Mutation breeding in leguminous crops has led to the induction of an improved L 114 soybean mutant that is shorter that the original variety but yield about 40% more. Several PAEC mungbean varieties characterized with long pods that are non-shattering were also induced. In asexually propagated crops, an increase in yield and chlorophyll mutants were obtained in sweet potatos. Likewise, chlorophyll mutant which look-like 'ornamental bromeliads' and a mutant with reduced spines have been developed in pineapple Queen variety. At present, we have started a new project in mutation breeding in ornamentals. Tissue culture is being utilized in our mutation breeding program. In the near future, radiation induced mutagenesis coupled with in vitro culture techniques on protoplast culture and somatic hybridization will be integrated into our mutation breeding program to facilitate the production of new crop varieties. (author)

Orthology prediction at scalable resolution by phylogenetic tree analysis

NARCIS (Netherlands)

Heijden, R.T.J.M. van der; Snel, B.; Noort, V. van; Huynen, M.A.

2007-01-01

BACKGROUND: Orthology is one of the cornerstones of gene function prediction. Dividing the phylogenetic relations between genes into either orthologs or paralogs is however an oversimplification. Already in two-species gene-phylogenies, the complicated, non-transitive nature of phylogenetic

Nanobits: customizable scanning probe tips

DEFF Research Database (Denmark)

Kumar, Rajendra; Shaik, Hassan Uddin; Sardan Sukas, Özlem

2009-01-01

We present here a proof-of-principle study of scanning probe tips defined by planar nanolithography and integrated with AFM probes using nanomanipulation. The so-called 'nanobits' are 2-4 mu m long and 120-150 nm thin flakes of Si3N4 or SiO2, fabricated by electron beam lithography and standard s...

Applying phylogenetic analysis to viral livestock diseases: moving beyond molecular typing.

Science.gov (United States)

Olvera, Alex; Busquets, Núria; Cortey, Marti; de Deus, Nilsa; Ganges, Llilianne; Núñez, José Ignacio; Peralta, Bibiana; Toskano, Jennifer; Dolz, Roser

2010-05-01

Changes in livestock production systems in recent years have altered the presentation of many diseases resulting in the need for more sophisticated control measures. At the same time, new molecular assays have been developed to support the diagnosis of animal viral disease. Nucleotide sequences generated by these diagnostic techniques can be used in phylogenetic analysis to infer phenotypes by sequence homology and to perform molecular epidemiology studies. In this review, some key elements of phylogenetic analysis are highlighted, such as the selection of the appropriate neutral phylogenetic marker, the proper phylogenetic method and different techniques to test the reliability of the resulting tree. Examples are given of current and future applications of phylogenetic reconstructions in viral livestock diseases. Copyright 2009 Elsevier Ltd. All rights reserved.

Cooling system for baby EBM scanning device

International Nuclear Information System (INIS)

Abd Halim Baijan; Muhammad Zahidee Taat; Abu Bakar Ghazali; Mohd Rizal Md Chulan; Rokiah Mohd Sabri; Leo Kwee Wah; Mohd Rizal Ibrahim; Lojius Lombigit; Azaman Ahmad

2009-01-01

Heat exchange of the scanning window of baby EBM is a critical factor for maintaining the integrity of the window material structure. As the titanium foil which was used as the scanning window, the maximum temperature accepted for the foil should be 200 degree C. This paper will discuss a simple method of Bernoulli principle to obtain the correct air blower capacity in order to reduce the heat of the scanning window of Baby EBM. It was found that the required air pressure and air speed of the blower are 2613.6 Pascal and 237.6 m3/h respectively for the electron accelerator of 0.14 MeV energy and 10 mA beam current. (Author)

Studying the evolutionary relationships and phylogenetic trees of 21 groups of tRNA sequences based on complex networks.

Science.gov (United States)

Wei, Fangping; Chen, Bowen

2012-03-01

To find out the evolutionary relationships among different tRNA sequences of 21 amino acids, 22 networks are constructed. One is constructed from whole tRNAs, and the other 21 networks are constructed from the tRNAs which carry the same amino acids. A new method is proposed such that the alignment scores of any two amino acids groups are determined by the average degree and the average clustering coefficient of their networks. The anticodon feature of isolated tRNA and the phylogenetic trees of 21 group networks are discussed. We find that some isolated tRNA sequences in 21 networks still connect with other tRNAs outside their group, which reflects the fact that those tRNAs might evolve by intercrossing among these 21 groups. We also find that most anticodons among the same cluster are only one base different in the same sites when S ≥ 70, and they stay in the same rank in the ladder of evolutionary relationships. Those observations seem to agree on that some tRNAs might mutate from the same ancestor sequences based on point mutation mechanisms.

Scanning Micromirror Platform Based on MEMS Technology for Medical Application

Directory of Open Access Journals (Sweden)

Eakkachai Pengwang

2016-02-01

Full Text Available This topical review discusses recent development and trends on scanning micromirrors for biomedical applications. This also includes a biomedical micro robot for precise manipulations in a limited volume. The characteristics of medical scanning micromirror are explained in general with the fundamental of microelectromechanical systems (MEMS for fabrication processes. Along with the explanations of mechanism and design, the principle of actuation are provided for general readers. In this review, several testing methodology and examples are described based on many types of actuators, such as, electrothermal actuators, electrostatic actuators, electromagnetic actuators, pneumatic actuators, and shape memory alloy. Moreover, this review provides description of the key fabrication processes and common materials in order to be a basic guideline for selecting micro-actuators. With recent developments on scanning micromirrors, performances of biomedical application are enhanced for higher resolution, high accuracy, and high dexterity. With further developments on integrations and control schemes, MEMS-based scanning micromirrors would be able to achieve a better performance for medical applications due to small size, ease in microfabrication, mass production, high scanning speed, low power consumption, mechanical stable, and integration compatibility.

Reconstruction of phylogenetic trees of prokaryotes using maximal common intervals.

Science.gov (United States)

Heydari, Mahdi; Marashi, Sayed-Amir; Tusserkani, Ruzbeh; Sadeghi, Mehdi

2014-10-01

One of the fundamental problems in bioinformatics is phylogenetic tree reconstruction, which can be used for classifying living organisms into different taxonomic clades. The classical approach to this problem is based on a marker such as 16S ribosomal RNA. Since evolutionary events like genomic rearrangements are not included in reconstructions of phylogenetic trees based on single genes, much effort has been made to find other characteristics for phylogenetic reconstruction in recent years. With the increasing availability of completely sequenced genomes, gene order can be considered as a new solution for this problem. In the present work, we applied maximal common intervals (MCIs) in two or more genomes to infer their distance and to reconstruct their evolutionary relationship. Additionally, measures based on uncommon segments (UCS's), i.e., those genomic segments which are not detected as part of any of the MCIs, are also used for phylogenetic tree reconstruction. We applied these two types of measures for reconstructing the phylogenetic tree of 63 prokaryotes with known COG (clusters of orthologous groups) families. Similarity between the MCI-based (resp. UCS-based) reconstructed phylogenetic trees and the phylogenetic tree obtained from NCBI taxonomy browser is as high as 93.1% (resp. 94.9%). We show that in the case of this diverse dataset of prokaryotes, tree reconstruction based on MCI and UCS outperforms most of the currently available methods based on gene orders, including breakpoint distance and DCJ. We additionally tested our new measures on a dataset of 13 closely-related bacteria from the genus Prochlorococcus. In this case, distances like rearrangement distance, breakpoint distance and DCJ proved to be useful, while our new measures are still appropriate for phylogenetic reconstruction. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Phylogenetic congruence between subtropical trees and their associated fungi

NARCIS (Netherlands)

Liu, Xubing; Liang, Minxia; Etienne, Rampal S.; Gilbert, Gregory S; Yu, Shixiao

2016-01-01

Recent studies have detected phylogenetic signals in pathogen-host networks for both soil-borne and leaf-infecting fungi, suggesting that pathogenic fungi may track or coevolve with their preferred hosts. However, a phylogenetically concordant relationship between multiple hosts and multiple fungi

One tree to link them all: a phylogenetic dataset for the European tetrapoda.

Science.gov (United States)

Roquet, Cristina; Lavergne, Sébastien; Thuiller, Wilfried

2014-08-08

Since the ever-increasing availability of phylogenetic informative data, the last decade has seen an upsurge of ecological studies incorporating information on evolutionary relationships among species. However, detailed species-level phylogenies are still lacking for many large groups and regions, which are necessary for comprehensive large-scale eco-phylogenetic analyses. Here, we provide a dataset of 100 dated phylogenetic trees for all European tetrapods based on a mixture of supermatrix and supertree approaches. Phylogenetic inference was performed separately for each of the main Tetrapoda groups of Europe except mammals (i.e. amphibians, birds, squamates and turtles) by means of maximum likelihood (ML) analyses of supermatrix applying a tree constraint at the family (amphibians and squamates) or order (birds and turtles) levels based on consensus knowledge. For each group, we inferred 100 ML trees to be able to provide a phylogenetic dataset that accounts for phylogenetic uncertainty, and assessed node support with bootstrap analyses. Each tree was dated using penalized-likelihood and fossil calibration. The trees obtained were well-supported by existing knowledge and previous phylogenetic studies. For mammals, we modified the most complete supertree dataset available on the literature to include a recent update of the Carnivora clade. As a final step, we merged the phylogenetic trees of all groups to obtain a set of 100 phylogenetic trees for all European Tetrapoda species for which data was available (91%). We provide this phylogenetic dataset (100 chronograms) for the purpose of comparative analyses, macro-ecological or community ecology studies aiming to incorporate phylogenetic information while accounting for phylogenetic uncertainty.

Always look on both sides: phylogenetic information conveyed by simple sequence repeat allele sequences.

Directory of Open Access Journals (Sweden)

Stéphanie Barthe

Full Text Available Simple sequence repeat (SSR markers are widely used tools for inferences about genetic diversity, phylogeography and spatial genetic structure. Their applications assume that variation among alleles is essentially caused by an expansion or contraction of the number of repeats and that, accessorily, mutations in the target sequences follow the stepwise mutation model (SMM. Generally speaking, PCR amplicon sizes are used as direct indicators of the number of SSR repeats composing an allele with the data analysis either ignoring the extent of allele size differences or assuming that there is a direct correlation between differences in amplicon size and evolutionary distance. However, without precisely knowing the kind and distribution of polymorphism within an allele (SSR and the associated flanking region (FR sequences, it is hard to say what kind of evolutionary message is conveyed by such a synthetic descriptor of polymorphism as DNA amplicon size. In this study, we sequenced several SSR alleles in multiple populations of three divergent tree genera and disentangled the types of polymorphisms contained in each portion of the DNA amplicon containing an SSR. The patterns of diversity provided by amplicon size variation, SSR variation itself, insertions/deletions (indels, and single nucleotide polymorphisms (SNPs observed in the FRs were compared. Amplicon size variation largely reflected SSR repeat number. The amount of variation was as large in FRs as in the SSR itself. The former contributed significantly to the phylogenetic information and sometimes was the main source of differentiation among individuals and populations contained by FR and SSR regions of SSR markers. The presence of mutations occurring at different rates within a marker's sequence offers the opportunity to analyse evolutionary events occurring on various timescales, but at the same time calls for caution in the interpretation of SSR marker data when the distribution of within

Assessing the relationships between phylogenetic and functional singularities in sharks (Chondrichthyes).

Science.gov (United States)

Cachera, Marie; Le Loc'h, François

2017-08-01

The relationships between diversity and ecosystem functioning have become a major focus of science. A crucial issue is to estimate functional diversity, as it is intended to impact ecosystem dynamics and stability. However, depending on the ecosystem, it may be challenging or even impossible to directly measure ecological functions and thus functional diversity. Phylogenetic diversity was recently under consideration as a proxy for functional diversity. Phylogenetic diversity is indeed supposed to match functional diversity if functions are conservative traits along evolution. However, in case of adaptive radiation and/or evolutive convergence, a mismatch may appear between species phylogenetic and functional singularities. Using highly threatened taxa, sharks, this study aimed to explore the relationships between phylogenetic and functional diversities and singularities. Different statistical computations were used in order to test both methodological issue (phylogenetic reconstruction) and overall a theoretical questioning: the predictive power of phylogeny for function diversity. Despite these several methodological approaches, a mismatch between phylogeny and function was highlighted. This mismatch revealed that (i) functions are apparently nonconservative in shark species, and (ii) phylogenetic singularity is not a proxy for functional singularity. Functions appeared to be not conservative along the evolution of sharks, raising the conservational challenge to identify and protect both phylogenetic and functional singular species. Facing the current rate of species loss, it is indeed of major importance to target phylogenetically singular species to protect genetic diversity and also functionally singular species in order to maintain particular functions within ecosystem.

Species divergence and phylogenetic variation of ecophysiological traits in lianas and trees.

Science.gov (United States)

Rios, Rodrigo S; Salgado-Luarte, Cristian; Gianoli, Ernesto

2014-01-01

The climbing habit is an evolutionary key innovation in plants because it is associated with enhanced clade diversification. We tested whether patterns of species divergence and variation of three ecophysiological traits that are fundamental for plant adaptation to light environments (maximum photosynthetic rate [A(max)], dark respiration rate [R(d)], and specific leaf area [SLA]) are consistent with this key innovation. Using data reported from four tropical forests and three temperate forests, we compared phylogenetic distance among species as well as the evolutionary rate, phylogenetic distance and phylogenetic signal of those traits in lianas and trees. Estimates of evolutionary rates showed that R(d) evolved faster in lianas, while SLA evolved faster in trees. The mean phylogenetic distance was 1.2 times greater among liana species than among tree species. Likewise, estimates of phylogenetic distance indicated that lianas were less related than by chance alone (phylogenetic evenness across 63 species), and trees were more related than expected by chance (phylogenetic clustering across 71 species). Lianas showed evenness for R(d), while trees showed phylogenetic clustering for this trait. In contrast, for SLA, lianas exhibited phylogenetic clustering and trees showed phylogenetic evenness. Lianas and trees showed patterns of ecophysiological trait variation among species that were independent of phylogenetic relatedness. We found support for the expected pattern of greater species divergence in lianas, but did not find consistent patterns regarding ecophysiological trait evolution and divergence. R(d) followed the species-level pattern, i.e., greater divergence/evolution in lianas compared to trees, while the opposite occurred for SLA and no pattern was detected for A(max). R(d) may have driven lianas' divergence across forest environments, and might contribute to diversification in climber clades.

Trends in lignin modification: a comprehensive analysis of the effects of genetic manipulations/mutations on lignification and vascular integrity

Science.gov (United States)

Anterola, Aldwin M.; Lewis, Norman G.

2002-01-01

A comprehensive assessment of lignin configuration in transgenic and mutant plants is long overdue. This review thus undertook the systematic analysis of trends manifested through genetic and mutational manipulations of the various steps associated with monolignol biosynthesis; this included consideration of the downstream effects on organized lignin assembly in the various cell types, on vascular function/integrity, and on plant growth and development. As previously noted for dirigent protein (homologs), distinct and sophisticated monolignol forming metabolic networks were operative in various cell types, tissues and organs, and form the cell-specific guaiacyl (G) and guaiacyl-syringyl (G-S) enriched lignin biopolymers, respectively. Regardless of cell type undergoing lignification, carbon allocation to the different monolignol pools is apparently determined by a combination of phenylalanine availability and cinnamate-4-hydroxylase/"p-coumarate-3-hydroxylase" (C4H/C3H) activities, as revealed by transcriptional and metabolic profiling. Downregulation of either phenylalanine ammonia lyase or cinnamate-4-hydroxylase thus predictably results in reduced lignin levels and impaired vascular integrity, as well as affecting related (phenylpropanoid-dependent) metabolism. Depletion of C3H activity also results in reduced lignin deposition, albeit with the latter being derived only from hydroxyphenyl (H) units, due to both the guaiacyl (G) and syringyl (S) pathways being blocked. Apparently the cells affected are unable to compensate for reduced G/S levels by increasing the amounts of H-components. The downstream metabolic networks for G-lignin enriched formation in both angiosperms and gymnosperms utilize specific cinnamoyl CoA O-methyltransferase (CCOMT), 4-coumarate:CoA ligase (4CL), cinnamoyl CoA reductase (CCR) and cinnamyl alcohol dehydrogenase (CAD) isoforms: however, these steps neither affect carbon allocation nor H/G designations, this being determined by C4H/C3H

Spatial phylogenetics of the vascular flora of Chile.

Science.gov (United States)

Scherson, Rosa A; Thornhill, Andrew H; Urbina-Casanova, Rafael; Freyman, William A; Pliscoff, Patricio A; Mishler, Brent D

2017-07-01

Current geographic patterns of biodiversity are a consequence of the evolutionary history of the lineages that comprise them. This study was aimed at exploring how evolutionary features of the vascular flora of Chile are distributed across the landscape. Using a phylogeny at the genus level for 87% of the Chilean vascular flora, and a geographic database of sample localities, we calculated phylogenetic diversity (PD), phylogenetic endemism (PE), relative PD (RPD), and relative PE (RPE). Categorical Analyses of Neo- and Paleo-Endemism (CANAPE) were also performed, using a spatial randomization to assess statistical significance. A cluster analysis using range-weighted phylogenetic turnover was used to compare among grid cells, and with known Chilean bioclimates. PD patterns were concordant with known centers of high taxon richness and the Chilean biodiversity hotspot. In addition, several other interesting areas of concentration of evolutionary history were revealed as potential conservation targets. The south of the country shows areas of significantly high RPD and a concentration of paleo-endemism, and the north shows areas of significantly low PD and RPD, and a concentration of neo-endemism. Range-weighted phylogenetic turnover shows high congruence with the main macrobioclimates of Chile. Even though the study was done at the genus level, the outcome provides an accurate outline of phylogenetic patterns that can be filled in as more fine-scaled information becomes available. Copyright © 2017 Elsevier Inc. All rights reserved.

A novel mutation of PAX3 in a Chinese family with Waardenburg syndrome.

Science.gov (United States)

Qin, Wei; Shu, Anli; Qian, Xueqing; Gao, Jianjun; Xing, Qinghe; Zhang, Juan; Zheng, Yonglan; Li, Xingwang; Li, Sheng; Feng, Guoyin; He, Lin

2006-08-28

The molecular characterization of 34 members of a Chinese family, with 22 members in four generations, affected with Waardenburg syndrome (WS1). A detailed family history and clinical data were collected. A genome-wide scan by two-point linkage analysis using more than 400 microsatellite markers in combination with haplotype analysis was performed. Mutation screening was carried out in the candidate gene by sequencing of amplified products. A maximum two-point lod score of 6.53 at theta = 0.00 was obtained with marker D2S2248. Haplotype analysis placed the WS1 locus to a 45.74 cM region between D2S117 and D2S206, in close proximity to the PAX3 gene on chromosome 2q35. Mutation screening in PAX3 identified a 701T > C mutation which converted a highly conserved Leu to Pro. This nucleotide alteration was neither seen in unaffected members of the family nor found in 50 unrelated control subjects. The present study identified a novel 701T > C mutation in PAX3. The mutation observed in this family highlights the phenotypic heterogeneity of the disorder.

Phylogenetic characterization of a biogas plant microbial community integrating clone library 16S-rDNA sequences and metagenome sequence data obtained by 454-pyrosequencing.

Science.gov (United States)

Kröber, Magdalena; Bekel, Thomas; Diaz, Naryttza N; Goesmann, Alexander; Jaenicke, Sebastian; Krause, Lutz; Miller, Dimitri; Runte, Kai J; Viehöver, Prisca; Pühler, Alfred; Schlüter, Andreas

2009-06-01

The phylogenetic structure of the microbial community residing in a fermentation sample from a production-scale biogas plant fed with maize silage, green rye and liquid manure was analysed by an integrated approach using clone library sequences and metagenome sequence data obtained by 454-pyrosequencing. Sequencing of 109 clones from a bacterial and an archaeal 16S-rDNA amplicon library revealed that the obtained nucleotide sequences are similar but not identical to 16S-rDNA database sequences derived from different anaerobic environments including digestors and bioreactors. Most of the bacterial 16S-rDNA sequences could be assigned to the phylum Firmicutes with the most abundant class Clostridia and to the class Bacteroidetes, whereas most archaeal 16S-rDNA sequences cluster close to the methanogen Methanoculleus bourgensis. Further sequences of the archaeal library most probably represent so far non-characterised species within the genus Methanoculleus. A similar result derived from phylogenetic analysis of mcrA clone sequences. The mcrA gene product encodes the alpha-subunit of methyl-coenzyme-M reductase involved in the final step of methanogenesis. BLASTn analysis applying stringent settings resulted in assignment of 16S-rDNA metagenome sequence reads to 62 16S-rDNA amplicon sequences thus enabling frequency of abundance estimations for 16S-rDNA clone library sequences. Ribosomal Database Project (RDP) Classifier processing of metagenome 16S-rDNA reads revealed abundance of the phyla Firmicutes, Bacteroidetes and Euryarchaeota and the orders Clostridiales, Bacteroidales and Methanomicrobiales. Moreover, a large fraction of 16S-rDNA metagenome reads could not be assigned to lower taxonomic ranks, demonstrating that numerous microorganisms in the analysed fermentation sample of the biogas plant are still unclassified or unknown.

Load Balancing Issues with Constructing Phylogenetic Trees using Neighbour-Joining Algorithm

International Nuclear Information System (INIS)

Al Mamun, S M

2012-01-01

Phylogenetic tree construction is one of the most important and interesting problems in bioinformatics. Constructing an efficient phylogenetic tree has always been a research issue. It needs to consider both the correctness and the speed of the tree construction. In this paper, we implemented the neighbour-joining algorithm, using Message Passing Interface (MPI) for constructing the phylogenetic tree. Performance is efficacious, comparing to the best sequential algorithm. From this paper, it would be clear to the researchers that how load balance can make a great effect for constructing phylogenetic trees using neighbour-joining algorithm.

Quartet-net: a quartet-based method to reconstruct phylogenetic networks.

Science.gov (United States)

Yang, Jialiang; Grünewald, Stefan; Wan, Xiu-Feng

2013-05-01

Phylogenetic networks can model reticulate evolutionary events such as hybridization, recombination, and horizontal gene transfer. However, reconstructing such networks is not trivial. Popular character-based methods are computationally inefficient, whereas distance-based methods cannot guarantee reconstruction accuracy because pairwise genetic distances only reflect partial information about a reticulate phylogeny. To balance accuracy and computational efficiency, here we introduce a quartet-based method to construct a phylogenetic network from a multiple sequence alignment. Unlike distances that only reflect the relationship between a pair of taxa, quartets contain information on the relationships among four taxa; these quartets provide adequate capacity to infer a more accurate phylogenetic network. In applications to simulated and biological data sets, we demonstrate that this novel method is robust and effective in reconstructing reticulate evolutionary events and it has the potential to infer more accurate phylogenetic distances than other conventional phylogenetic network construction methods such as Neighbor-Joining, Neighbor-Net, and Split Decomposition. This method can be used in constructing phylogenetic networks from simple evolutionary events involving a few reticulate events to complex evolutionary histories involving a large number of reticulate events. A software called "Quartet-Net" is implemented and available at http://sysbio.cvm.msstate.edu/QuartetNet/.

Simplifying the detection of MUTYH mutations by high resolution melting analysis

International Nuclear Information System (INIS)

López-Villar, Isabel; Martínez-López, Joaquín; Ayala, Rosa; Wesselink, Jan; Morillas, Juan Diego; López, Elena; Marín, José Carlos; Díaz-Tasende, José; González, Sara; Robles, Luis

2010-01-01

MUTYH-associated polyposis (MAP) is a disorder caused by bi-allelic germline MUTYH mutation, characterized by multiple colorectal adenomas. In order to identify mutations in MUTYH gene we applied High Resolution Melting (HRM) genotyping. HRM analysis is extensively employed as a scanning method for the detection of heterozygous mutations. Therefore, we applied HRM to show effectiveness in detecting homozygous mutations for these clinically important and frequent patients. In this study, we analyzed phenotype and genotype data from 82 patients, with multiple (>= 10) synchronous (19/82) or metachronous (63/82) adenomas and negative APC study (except one case). Analysis was performed by HRM-PCR and direct sequencing, in order to identify mutations in MUTYH exons 7, 12 and 13, where the most prevalent mutations are located. In monoallelic mutation carriers, we evaluated entire MUTYH gene in search of another possible alteration. HRM-PCR was performed with strict conditions in several rounds: the first one to discriminate the heteroduplex patterns and homoduplex patterns and the next ones, in order to refine and confirm parameters. The genotypes obtained were correlated to phenotypic features (number of adenomas (synchronous or metachronous), colorectal cancer (CRC) and family history). MUTYH germline mutations were found in 15.8% (13/82) of patients. The hot spots, Y179C (exon 7) and G396D (exon 13), were readily identified and other mutations were also detected. Each mutation had a reproducible melting profile by HRM, both heterozygous mutations and homozygous mutations. In our study of 82 patients, biallelic mutation is associated with being a carrier of ≥10 synchronous polyps (p = 0.05) and there is no association between biallelic mutation and CRC (p = 0.39) nor family history (p = 0.63). G338H non-pathogenic polymorphism (exon 12) was found in 23.1% (19/82) of patients. In all cases there was concordance between HRM (first and subsequent rounds) and sequencing

Pheochromocytomatosis associated with a novel TMEM127 mutation

Directory of Open Access Journals (Sweden)

Run Yu

2017-05-01

Full Text Available Pheochromocytomatosis, a very rare form of pheochromocytoma recurrence, refers to new, multiple, and often small pheochromocytomas growing in and around the surgical resection bed of a previous adrenalectomy for a solitary pheochromocytoma. We here report a case of pheochromocytomatosis in a 70-year-old female. At age 64 years, she was diagnosed with a 6-cm right pheochromocytoma. She underwent laparoscopic right adrenalectomy, during which the tumor capsule was ruptured. At age 67 years, CT of abdomen did not detect recurrence. At age 69 years, she began experiencing episodes of headache and diaphoresis. At age 70 years, biochemical markers of pheochromocytoma became elevated with normal calcitonin level. CT revealed multiple nodules of various sizes in the right adrenal fossa, some of which were positive on metaiodobenzylguanidine (MIBG scan. She underwent open resection of pheochromocytomatosis. Histological examination confirmed numerous pheochromocytomas ranging 0.1–1.2 cm in size. Next-generation sequencing of a panel of genes found a novel heterozygous germline c.570delC mutation in TMEM127, one of the genes that, if mutated, confers susceptibility to syndromic pheochromocytoma. Molecular analysis showed that the c.570delC mutation is likely pathogenic. Our case highlights the typical presentation of pheochromocytomatosis, a rare complication of adrenalectomy for pheochromocytoma. Previous cases and ours collectively demonstrate that tumor capsule rupture during adrenalectomy is a risk factor for pheochromocytomatosis. We also report a novel TMEM127 mutation in this case.

A Scanning scheimpflug lidar system developed for urban pollution monitoring

Science.gov (United States)

Yang, Yang; Guan, Peng; Mei, Liang

2018-04-01

A scanning Scheimpflug lidar system based on the Scheimpflug principle has been developed by employing a high power multimode 808 nm laser diode and a highly integrated CMOS sensor in Dalian University of Technology, Dalian, Northern China. Atmospheric scanning measurements in urban area were performed for the studies of particle emission sources.

Effect of endogenous carotenoids on “adaptive” mutation in Escherichia coli FC40

Science.gov (United States)

Bridges, Bryn A.; Foster, Patricia L.; Timms, Andrew R.

2010-01-01

The appearance over many days of Lac+ frameshift mutations in Escherichia coli strain FC40 incubated on lactose selection plates is a classic example of apparent “adaptive” mutation in an episomal gene. We show that endogenously overproduced carotenoids reduce adaptive mutation under selective conditions by a factor of around two. Carotenoids are known to scavenge singlet oxygen suggesting that the accumulation of oxidative base damage may be an integral part of the adaptive mutation phenomenon. If so, the lesion cannot be 7,8-dihydro-8-oxoguanine since adaptive mutation in FC40 is unaffected by mutM and mutY mutations. If active oxygen species such as singlet oxygen are involved in adaptive mutation then they should also induce frameshift mutations in FC40 under non-selective conditions. We show that such mutations can be induced under non-selective conditions by protoporphyrin photosensitisation and that this photodynamic induction is reduced by a factor of just over two when endogenous carotenoids are present. We argue that the involvement of oxidative damage would in no way be inconsistent with current understanding of the mechanism of adaptive mutation and the role of DNA polymerases. PMID:11166030

Mycorrhizae support oaks growing in a phylogenetically distant neighbourhood

NARCIS (Netherlands)

Yguel, B.; Courty, P.E.; Jactel, H.; Pan, X.; Butenschoen, O.; Murray, P.J.; Prinzing, A.

2014-01-01

Host-plants may rarely leave their ancestral niche and in which case they tend to be surrounded by phylogenetically distant neighbours. Phylogenetically isolated host-plants might share few mutualists with their neighbours and might suffer from a decrease in mutualist support. In addition host

The protist Trichomonas vaginalis harbors multiple lineages of transcriptionally active Mutator-like elements

Directory of Open Access Journals (Sweden)

Pereira Gonçalo AG

2009-07-01

Full Text Available Abstract Background For three decades the Mutator system was thought to be exclusive of plants, until the first homolog representatives were characterized in fungi and in early-diverging amoebas earlier in this decade. Results Here, we describe and characterize four families of Mutator-like elements in a new eukaryotic group, the Parabasalids. These Trichomonas vaginalis Mutator- like elements, or TvMULEs, are active in T. vaginalis and patchily distributed among 12 trichomonad species and isolates. Despite their relatively distinctive amino acid composition, the inclusion of the repeats TvMULE1, TvMULE2, TvMULE3 and TvMULE4 into the Mutator superfamily is justified by sequence, structural and phylogenetic analyses. In addition, we identified three new TvMULE-related sequences in the genome sequence of Candida albicans. While TvMULE1 is a member of the MuDR clade, predominantly from plants, the other three TvMULEs, together with the C. albicans elements, represent a new and quite distinct Mutator lineage, which we named TvCaMULEs. The finding of TvMULE1 sequence inserted into other putative repeat suggests the occurrence a novel TE family not yet described. Conclusion These findings expand the taxonomic distribution and the range of functional motif of MULEs among eukaryotes. The characterization of the dynamics of TvMULEs and other transposons in this organism is of particular interest because it is atypical for an asexual species to have such an extreme level of TE activity; this genetic landscape makes an interesting case study for causes and consequences of such activity. Finally, the extreme repetitiveness of the T. vaginalis genome and the remarkable degree of sequence identity within its repeat families highlights this species as an ideal system to characterize new transposable elements.

Novel USH2A mutations in Israeli patients with retinitis pigmentosa and Usher syndrome type 2.

Science.gov (United States)

Kaiserman, Nadia; Obolensky, Alexey; Banin, Eyal; Sharon, Dror

2007-02-01

To identify USH2A mutations in Israeli patients with autosomal-recessive Usher syndrome type 2 (USH2) and retinitis pigmentosa (RP). Patients from 95 families with RP and 4 with USH2 were clinically evaluated. USH2A exons 2-72 were scanned for mutations using single-strand conformation and sequencing analyses. The frequency of novel missense changes was determined in patients and controls using restriction endonucleases. The analysis revealed 3 USH2A mutations, 2 of which are novel, in 2 families with USH2 and a large family (MOL0051) with both USH2 and RP. Compound heterozygotes for 2 null mutations (Thr80fs and Arg737stop) in MOL0051 suffered from USH2 while compound heterozygotes for 1 of the null mutations and a novel missense mutation (Gly4674Arg) had nonsyndromic RP. Our results support the involvement of USH2A in nonsyndromic RP and we report here of a second, novel, missense mutation in this gene causing autosomal-recessive RP. Possible involvement of USH2A should be considered in the molecular genetic evaluation of patients with autosomal-recessive RP. Understanding the mechanism by which different USH2A mutations cause either USH2 or RP may assist in the development of novel therapeutic approaches.

Whole Genome Phylogenetic Tree Reconstruction using Colored de Bruijn Graphs

OpenAIRE

Lyman, Cole

2017-01-01

We present kleuren, a novel assembly-free method to reconstruct phylogenetic trees using the Colored de Bruijn Graph. kleuren works by constructing the Colored de Bruijn Graph and then traversing it, finding bubble structures in the graph that provide phylogenetic signal. The bubbles are then aligned and concatenated to form a supermatrix, from which a phylogenetic tree is inferred. We introduce the algorithm that kleuren uses to accomplish this task, and show its performance on reconstructin...

Distance-Based Phylogenetic Methods Around a Polytomy.

Science.gov (United States)

Davidson, Ruth; Sullivant, Seth

2014-01-01

Distance-based phylogenetic algorithms attempt to solve the NP-hard least-squares phylogeny problem by mapping an arbitrary dissimilarity map representing biological data to a tree metric. The set of all dissimilarity maps is a Euclidean space properly containing the space of all tree metrics as a polyhedral fan. Outputs of distance-based tree reconstruction algorithms such as UPGMA and neighbor-joining are points in the maximal cones in the fan. Tree metrics with polytomies lie at the intersections of maximal cones. A phylogenetic algorithm divides the space of all dissimilarity maps into regions based upon which combinatorial tree is reconstructed by the algorithm. Comparison of phylogenetic methods can be done by comparing the geometry of these regions. We use polyhedral geometry to compare the local nature of the subdivisions induced by least-squares phylogeny, UPGMA, and neighbor-joining when the true tree has a single polytomy with exactly four neighbors. Our results suggest that in some circumstances, UPGMA and neighbor-joining poorly match least-squares phylogeny.

The power and pitfalls of HIV phylogenetics in public health.

Science.gov (United States)

Brooks, James I; Sandstrom, Paul A

2013-07-25

Phylogenetics is the application of comparative studies of genetic sequences in order to infer evolutionary relationships among organisms. This tool can be used as a form of molecular epidemiology to enhance traditional population-level communicable disease surveillance. Phylogenetic study has resulted in new paradigms being created in the field of communicable diseases and this commentary aims to provide the reader with an explanation of how phylogenetics can be used in tracking infectious diseases. Special emphasis will be placed upon the application of phylogenetics as a tool to help elucidate HIV transmission patterns and the limitations to these methods when applied to forensic analysis. Understanding infectious disease epidemiology in order to prevent new transmissions is the sine qua non of public health. However, with increasing epidemiological resolution, there may be an associated potential loss of privacy to the individual. It is within this context that we aim to promote the discussion on how to use phylogenetics to achieve important public health goals, while at the same time protecting the rights of the individual.

Sequence and phylogenetic analysis of virulent Newcastle disease virus isolates from Pakistan during 2009–2013 reveals circulation of new sub genotype

International Nuclear Information System (INIS)

Siddique, Naila; Naeem, Khalid; Abbas, Muhammad Athar; Ali Malik, Akbar; Rashid, Farooq; Rafique, Saba; Ghafar, Abdul; Rehman, Abdul

2013-01-01

Despite observing the standard bio-security measures at commercial poultry farms and extensive use of Newcastle disease vaccines, a new genotype VII-f of Newcastle disease virus (NDV) got introduced in Pakistan during 2011. In this regard 300 ND outbreaks recorded so far have resulted into huge losses of approximately USD 200 million during 2011–2013. A total of 33 NDV isolates recovered during 2009–2013 throughout Pakistan were characterized biologically and phylogenetically. The phylogenetic analysis revealed a new velogenic sub genotype VII-f circulating in commercial and domestic poultry along with the earlier reported sub genotype VII-b. Partial sequencing of Fusion gene revealed two types of cleavage site motifs; lentogenic 112 GRQGRL 117 and velogenic 112 RRQKRF 117 along with some point mutations indicative of genetic diversity. We report here a new sub genotype of virulent NDV circulating in commercial and backyard poultry in Pakistan and provide evidence for the possible genetic diversity which may be causing new NDV out breaks. - Highlights: • The first report of isolation of new genotype VII-f of virulent Newcastle disease virus (NDV) in Pakistan. • We report the partial Fusion gene sequences of new genotype VII-f of virulent NDV from Pakistan. • We report the phylogenetic relationship of new NDV strains with reported NDV strains. • Provide outbreak history of new virulent NDV strain in commercial and backyard poultry in Pakistan. • We provide possible evidence for the role of backyard poultry in NDV outbreaks

An integrated system for large scale scanning of nuclear emulsions

Energy Technology Data Exchange (ETDEWEB)

Bozza, Cristiano, E-mail: kryss@sa.infn.it [University of Salerno and INFN, via Ponte Don Melillo, Fisciano 84084 (Italy); D’Ambrosio, Nicola [Laboratori Nazionali del Gran Sasso, S.S. 17 BIS km 18.910, Assergi (AQ) 67010 (Italy); De Lellis, Giovanni [University of Napoli and INFN, Complesso Universitario di Monte Sant' Angelo, via Cintia Ed. G, Napoli 80126 (Italy); De Serio, Marilisa [University of Bari and INFN, via E. Orabona 4, Bari 70125 (Italy); Di Capua, Francesco [INFN Napoli, Complesso Universitario di Monte Sant' Angelo, via Cintia Ed. G, Napoli 80126 (Italy); Di Crescenzo, Antonia [University of Napoli and INFN, Complesso Universitario di Monte Sant' Angelo, via Cintia Ed. G, Napoli 80126 (Italy); Di Ferdinando, Donato [INFN Bologna, viale B. Pichat 6/2, Bologna 40127 (Italy); Di Marco, Natalia [Laboratori Nazionali del Gran Sasso, S.S. 17 BIS km 18.910, Assergi (AQ) 67010 (Italy); Esposito, Luigi Salvatore [Laboratori Nazionali del Gran Sasso, now at CERN, Geneva (Switzerland); Fini, Rosa Anna [INFN Bari, via E. Orabona 4, Bari 70125 (Italy); Giacomelli, Giorgio [University of Bologna and INFN, viale B. Pichat 6/2, Bologna 40127 (Italy); Grella, Giuseppe [University of Salerno and INFN, via Ponte Don Melillo, Fisciano 84084 (Italy); Ieva, Michela [University of Bari and INFN, via E. Orabona 4, Bari 70125 (Italy); Kose, Umut [INFN Padova, via Marzolo 8, Padova (PD) 35131 (Italy); Longhin, Andrea; Mauri, Nicoletta [INFN Laboratori Nazionali di Frascati, via E. Fermi 40, Frascati (RM) 00044 (Italy); Medinaceli, Eduardo [University of Padova and INFN, via Marzolo 8, Padova (PD) 35131 (Italy); Monacelli, Piero [University of L' Aquila and INFN, via Vetoio Loc. Coppito, L' Aquila (AQ) 67100 (Italy); Muciaccia, Maria Teresa; Pastore, Alessandra [University of Bari and INFN, via E. Orabona 4, Bari 70125 (Italy); and others

2013-03-01

The European Scanning System, developed to analyse nuclear emulsions at high speed, has been completed with the development of a high level software infrastructure to automate and support large-scale emulsion scanning. In one year, an average installation is capable of performing data-taking and online analysis on a total surface ranging from few m{sup 2} to tens of m{sup 2}, acquiring many billions of tracks, corresponding to several TB. This paper focuses on the procedures that have been implemented and on their impact on physics measurements. The system proved robust, reliable, fault-tolerant and user-friendly, and seldom needs assistance. A dedicated relational Data Base system is the backbone of the whole infrastructure, storing data themselves and not only catalogues of data files, as in common practice, being a unique case in high-energy physics DAQ systems. The logical organisation of the system is described and a summary is given of the physics measurement that are readily available by automated processing.

An integrated system for large scale scanning of nuclear emulsions

International Nuclear Information System (INIS)

Bozza, Cristiano; D’Ambrosio, Nicola; De Lellis, Giovanni; De Serio, Marilisa; Di Capua, Francesco; Di Crescenzo, Antonia; Di Ferdinando, Donato; Di Marco, Natalia; Esposito, Luigi Salvatore; Fini, Rosa Anna; Giacomelli, Giorgio; Grella, Giuseppe; Ieva, Michela; Kose, Umut; Longhin, Andrea; Mauri, Nicoletta; Medinaceli, Eduardo; Monacelli, Piero; Muciaccia, Maria Teresa; Pastore, Alessandra

2013-01-01

The European Scanning System, developed to analyse nuclear emulsions at high speed, has been completed with the development of a high level software infrastructure to automate and support large-scale emulsion scanning. In one year, an average installation is capable of performing data-taking and online analysis on a total surface ranging from few m 2 to tens of m 2 , acquiring many billions of tracks, corresponding to several TB. This paper focuses on the procedures that have been implemented and on their impact on physics measurements. The system proved robust, reliable, fault-tolerant and user-friendly, and seldom needs assistance. A dedicated relational Data Base system is the backbone of the whole infrastructure, storing data themselves and not only catalogues of data files, as in common practice, being a unique case in high-energy physics DAQ systems. The logical organisation of the system is described and a summary is given of the physics measurement that are readily available by automated processing

Genome-wide SNP scan of pooled DNA reveals nonsense mutation in FGF20 in the scaleless line of featherless chickens

Directory of Open Access Journals (Sweden)

Wells Kirsty L

2012-06-01

Full Text Available Abstract Background Scaleless (sc/sc chickens carry a single recessive mutation that causes a lack of almost all body feathers, as well as foot scales and spurs, due to a failure of skin patterning during embryogenesis. This spontaneous mutant line, first described in the 1950s, has been used extensively to explore the tissue interactions involved in ectodermal appendage formation in embryonic skin. Moreover, the trait is potentially useful in tropical agriculture due to the ability of featherless chickens to tolerate heat, which is at present a major constraint to efficient poultry meat production in hot climates. In the interests of enhancing our understanding of feather placode development, and to provide the poultry industry with a strategy to breed heat-tolerant meat-type chickens (broilers, we mapped and identified the sc mutation. Results Through a cost-effective and labour-efficient SNP array mapping approach using DNA from sc/sc and sc/+ blood sample pools, we map the sc trait to chromosome 4 and show that a nonsense mutation in FGF20 is completely associated with the sc/sc phenotype. This mutation, common to all sc/sc individuals and absent from wild type, is predicted to lead to loss of a highly conserved region of the FGF20 protein important for FGF signalling. In situ hybridisation and quantitative RT-PCR studies reveal that FGF20 is epidermally expressed during the early stages of feather placode patterning. In addition, we describe a dCAPS genotyping assay based on the mutation, developed to facilitate discrimination between wild type and sc alleles. Conclusions This work represents the first loss of function genetic evidence supporting a role for FGF ligand signalling in feather development, and suggests FGF20 as a novel central player in the development of vertebrate skin appendages, including hair follicles and exocrine glands. In addition, this is to our knowledge the first report describing the use of the chicken SNP array to

Model Identification of Integrated ARMA Processes

Science.gov (United States)

Stadnytska, Tetiana; Braun, Simone; Werner, Joachim

2008-01-01

This article evaluates the Smallest Canonical Correlation Method (SCAN) and the Extended Sample Autocorrelation Function (ESACF), automated methods for the Autoregressive Integrated Moving-Average (ARIMA) model selection commonly available in current versions of SAS for Windows, as identification tools for integrated processes. SCAN and ESACF can…

The IARC TP53 mutation database: a resource for studying the significance of TP53 mutations in human cancers

Directory of Open Access Journals (Sweden)

Magali Olivier

2007-02-01

Full Text Available

The tumor suppressor gene TP53 is frequently inactivated by gene mutations in many types of human sporadic cancers, and inherited TP53 mutations predispose to a wide spectrum of early-onset tumors (Li-Fraumeni et Li-Fraumenilike Syndromes. All TP53 gene variations (somatic and germline mutations, as well as polymorphisms that are reported in the scientific literature or in SNP databases are compiled in the IARC TP53 Database. This database provides structured data and analysis tools to study mutation patterns in human cancers and cell-lines and to investigate the clinical impact of mutations. It contains annotations related to the clinical and pathological characteristics of tumors, as well as the demographics and carcinogen exposure of patients. The IARC TP53 web site (http://www-p53.iarc.fr/ provides a search interface for the core database and includes a comprehensive user guide, a slideshow on TP53 mutations in human cancer, protocols and references for sequencing TP53 gene, and links to relevant publications and bioinformatics databases. The database interface allows download of entire data sets and propose various tools for the selection, analysis and downloads of specific sets of data according to user's query.

Recently, new annotations on the functional properties of mutant p53 proteins have been integrated in this database. Indeed, the most frequent TP53 alterations observed in cancers (75% are missense mutations that result in the production of a mutant protein that differ from the wildtype by one single amino-acid. The characterization of the biological activities of these mutant proteins is thus very important. Over the last ten years, a great amount of systematic data has been generated from experimental assays performed in

A Universal Phylogenetic Tree.

Science.gov (United States)

Offner, Susan

2001-01-01

Presents a universal phylogenetic tree suitable for use in high school and college-level biology classrooms. Illustrates the antiquity of life and that all life is related, even if it dates back 3.5 billion years. Reflects important evolutionary relationships and provides an exciting way to learn about the history of life. (SAH)

Efficient scanning of thick lead vessels

International Nuclear Information System (INIS)

Raghunath, V.M.; Bhatnagar, P.K.; Meenakshisundaram, V.

1978-01-01

Lead containers fabricated for transport of radioactive materials need to be evaluated for their shielding integrity. The common method of locating a strong gamma source inside the vessel and scanning the external surface by conventional detectors suffers from high radiation dose and low sensitivity. A new method has been proposed and tried. It is found to be more efficient. In the new method, 60 Co source is loaded at the centre of the lead vessel and the outer surface is scanned by NaI(Tl) detector. The transmitted virgin flux is scanned under the 60 Co channel in a single channel analyser. An area of 25 cm 2 is scanned for 10 to 20 seconds each time. The source strength required is considerably reduced by a factor of 10 or more as compared to the common method and external dose rates do not exceed 50 mR/h (130 nC. kg -1 h -1 ) on the vessel surface. The advantages are improved sensitivity, no interference from scattered radiation and assurance in repeatability of measurements. (M.G.B.)

Evolution of the brain and phylogenetic development of Mrican ...

African Journals Online (AJOL)

Evolution of the brain and phylogenetic development of Mrican Bovidae. Henriette Oboussier. Zoological Institute and Museum, University of Hamburg. Evidence drawn from the study of 270 brains of 54 species and subspecies of African Bovidae makes it possible to base phylogenetic relationships on the similarities in the ...

Cis-regulatory somatic mutations and gene-expression alteration in B-cell lymphomas.

Science.gov (United States)

Mathelier, Anthony; Lefebvre, Calvin; Zhang, Allen W; Arenillas, David J; Ding, Jiarui; Wasserman, Wyeth W; Shah, Sohrab P

2015-04-23

With the rapid increase of whole-genome sequencing of human cancers, an important opportunity to analyze and characterize somatic mutations lying within cis-regulatory regions has emerged. A focus on protein-coding regions to identify nonsense or missense mutations disruptive to protein structure and/or function has led to important insights; however, the impact on gene expression of mutations lying within cis-regulatory regions remains under-explored. We analyzed somatic mutations from 84 matched tumor-normal whole genomes from B-cell lymphomas with accompanying gene expression measurements to elucidate the extent to which these cancers are disrupted by cis-regulatory mutations. We characterize mutations overlapping a high quality set of well-annotated transcription factor binding sites (TFBSs), covering a similar portion of the genome as protein-coding exons. Our results indicate that cis-regulatory mutations overlapping predicted TFBSs are enriched in promoter regions of genes involved in apoptosis or growth/proliferation. By integrating gene expression data with mutation data, our computational approach culminates with identification of cis-regulatory mutations most likely to participate in dysregulation of the gene expression program. The impact can be measured along with protein-coding mutations to highlight key mutations disrupting gene expression and pathways in cancer. Our study yields specific genes with disrupted expression triggered by genomic mutations in either the coding or the regulatory space. It implies that mutated regulatory components of the genome contribute substantially to cancer pathways. Our analyses demonstrate that identifying genomically altered cis-regulatory elements coupled with analysis of gene expression data will augment biological interpretation of mutational landscapes of cancers.

A de novo nonsense PDGFB mutation causing idiopathic basal ganglia calcification with laryngeal dystonia.

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Nicolas, Gaël; Jacquin, Agnès; Thauvin-Robinet, Christel; Rovelet-Lecrux, Anne; Rouaud, Olivier; Pottier, Cyril; Aubriot-Lorton, Marie-Hélène; Rousseau, Stéphane; Wallon, David; Duvillard, Christian; Béjot, Yannick; Frébourg, Thierry; Giroud, Maurice; Campion, Dominique; Hannequin, Didier

2014-10-01

Idiopathic basal ganglia calcification (IBGC) is characterized by brain calcification and a wide variety of neurologic and psychiatric symptoms. In families with autosomal dominant inheritance, three causative genes have been identified: SLC20A2, PDGFRB, and, very recently, PDGFB. Whereas in clinical practice sporadic presentation of IBGC is frequent, well-documented reports of true sporadic occurrence are rare. We report the case of a 20-year-old woman who presented laryngeal dystonia revealing IBGC. Her healthy parents' CT scans were both normal. We identified in the proband a new nonsense mutation in exon 4 of PDGFB, c.439C>T (p.Gln147*), which was absent from the parents' DNA. This mutation may result in a loss-of-function of PDGF-B, which has been shown to cause IBGC in humans and to disrupt the blood-brain barrier in mice, resulting in brain calcification. The c.439C>T mutation is located between two previously reported nonsense mutations, c.433C>T (p.Gln145*) and c.445C>T (p.Arg149*), on a region that could be a hot spot for de novo mutations. We present the first full demonstration of the de novo occurrence of an IBGC-causative mutation in a sporadic case.

Orthology prediction at scalable resolution by phylogenetic tree analysis

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Huynen Martijn A

2007-03-01

Full Text Available Abstract Background Orthology is one of the cornerstones of gene function prediction. Dividing the phylogenetic relations between genes into either orthologs or paralogs is however an oversimplification. Already in two-species gene-phylogenies, the complicated, non-transitive nature of phylogenetic relations results in inparalogs and outparalogs. For situations with more than two species we lack semantics to specifically describe the phylogenetic relations, let alone to exploit them. Published procedures to extract orthologous groups from phylogenetic trees do not allow identification of orthology at various levels of resolution, nor do they document the relations between the orthologous groups. Results We introduce "levels of orthology" to describe the multi-level nature of gene relations. This is implemented in a program LOFT (Levels of Orthology From Trees that assigns hierarchical orthology numbers to genes based on a phylogenetic tree. To decide upon speciation and gene duplication events in a tree LOFT can be instructed either to perform classical species-tree reconciliation or to use the species overlap between partitions in the tree. The hierarchical orthology numbers assigned by LOFT effectively summarize the phylogenetic relations between genes. The resulting high-resolution orthologous groups are depicted in colour, facilitating visual inspection of (large trees. A benchmark for orthology prediction, that takes into account the varying levels of orthology between genes, shows that the phylogeny-based high-resolution orthology assignments made by LOFT are reliable. Conclusion The "levels of orthology" concept offers high resolution, reliable orthology, while preserving the relations between orthologous groups. A Windows as well as a preliminary Java version of LOFT is available from the LOFT website http://www.cmbi.ru.nl/LOFT.

The macroecology of phylogenetically structured hummingbird-plant networks

DEFF Research Database (Denmark)

González, Ana M. Martín; Dalsgaard, Bo; Nogues, David Bravo

2015-01-01

Aim To investigate the association between hummingbird–plant network structure and species richness, phylogenetic signal on species' interaction pattern, insularity and historical and current climate. Location Fifty-four communities along a c. 10,000 km latitudinal gradient across the Americas (39...... approach, we examined the influence of species richness, phylogenetic signal, insularity and current and historical climate conditions on network structure (null-model-corrected specialization and modularity). Results Phylogenetically related species, especially plants, showed a tendency to interact...... with a similar array of mutualistic partners. The spatial variation in network structure exhibited a constant association with species phylogeny (R2 = 0.18–0.19); however, network structure showed the strongest association with species richness and environmental factors (R2 = 0.20–0.44 and R2 = 0...

Clinical and functional characterization of a patient carrying a compound heterozygous pericentrin mutation and a heterozygous IGF1 receptor mutation.

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Eva Müller

Full Text Available Intrauterine and postnatal longitudinal growth is controlled by a strong genetic component that regulates a complex network of endocrine factors integrating them with cellular proliferation, differentiation and apoptotic processes in target tissues, particularly the growth centers of the long bones. Here we report on a patient born small for gestational age (SGA with severe, proportionate postnatal growth retardation, discreet signs of skeletal dysplasia, microcephaly and moyamoya disease. Initial genetic evaluation revealed a novel heterozygous IGF1R p.Leu1361Arg mutation affecting a highly conserved residue with the insulin-like growth factor type 1 receptor suggestive for a disturbance within the somatotropic axis. However, because the mutation did not co-segregate with the phenotype and functional characterization did not reveal an obvious impairment of the ligand depending major IGF1R signaling capabilities a second-site mutation was assumed. Mutational screening of components of the somatotropic axis, constituents of the IGF signaling system and factors involved in cellular proliferation, which are described or suggested to provoke syndromic dwarfism phenotypes, was performed. Two compound heterozygous PCNT mutations (p.[Arg585X];[Glu1774X] were identified leading to the specification of the diagnosis to MOPD II. These investigations underline the need for careful assessment of all available information to derive a firm diagnosis from a sequence aberration.

Clinical and functional characterization of a patient carrying a compound heterozygous pericentrin mutation and a heterozygous IGF1 receptor mutation.

Science.gov (United States)

Müller, Eva; Dunstheimer, Desiree; Klammt, Jürgen; Friebe, Daniela; Kiess, Wieland; Kratzsch, Jürgen; Kruis, Tassilo; Laue, Sandy; Pfäffle, Roland; Wallborn, Tillmann; Heidemann, Peter H

2012-01-01

Intrauterine and postnatal longitudinal growth is controlled by a strong genetic component that regulates a complex network of endocrine factors integrating them with cellular proliferation, differentiation and apoptotic processes in target tissues, particularly the growth centers of the long bones. Here we report on a patient born small for gestational age (SGA) with severe, proportionate postnatal growth retardation, discreet signs of skeletal dysplasia, microcephaly and moyamoya disease. Initial genetic evaluation revealed a novel heterozygous IGF1R p.Leu1361Arg mutation affecting a highly conserved residue with the insulin-like growth factor type 1 receptor suggestive for a disturbance within the somatotropic axis. However, because the mutation did not co-segregate with the phenotype and functional characterization did not reveal an obvious impairment of the ligand depending major IGF1R signaling capabilities a second-site mutation was assumed. Mutational screening of components of the somatotropic axis, constituents of the IGF signaling system and factors involved in cellular proliferation, which are described or suggested to provoke syndromic dwarfism phenotypes, was performed. Two compound heterozygous PCNT mutations (p.[Arg585X];[Glu1774X]) were identified leading to the specification of the diagnosis to MOPD II. These investigations underline the need for careful assessment of all available information to derive a firm diagnosis from a sequence aberration.

A structural systems biology approach for quantifying the systemic consequences of missense mutations in proteins.

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Tammy M K Cheng

Full Text Available Gauging the systemic effects of non-synonymous single nucleotide polymorphisms (nsSNPs is an important topic in the pursuit of personalized medicine. However, it is a non-trivial task to understand how a change at the protein structure level eventually affects a cell's behavior. This is because complex information at both the protein and pathway level has to be integrated. Given that the idea of integrating both protein and pathway dynamics to estimate the systemic impact of missense mutations in proteins remains predominantly unexplored, we investigate the practicality of such an approach by formulating mathematical models and comparing them with experimental data to study missense mutations. We present two case studies: (1 interpreting systemic perturbation for mutations within the cell cycle control mechanisms (G2 to mitosis transition for yeast; (2 phenotypic classification of neuron-related human diseases associated with mutations within the mitogen-activated protein kinase (MAPK pathway. We show that the application of simplified mathematical models is feasible for understanding the effects of small sequence changes on cellular behavior. Furthermore, we show that the systemic impact of missense mutations can be effectively quantified as a combination of protein stability change and pathway perturbation.

Exploring the relationship between sequence similarity and accurate phylogenetic trees.

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Cantarel, Brandi L; Morrison, Hilary G; Pearson, William

2006-11-01

We have characterized the relationship between accurate phylogenetic reconstruction and sequence similarity, testing whether high levels of sequence similarity can consistently produce accurate evolutionary trees. We generated protein families with known phylogenies using a modified version of the PAML/EVOLVER program that produces insertions and deletions as well as substitutions. Protein families were evolved over a range of 100-400 point accepted mutations; at these distances 63% of the families shared significant sequence similarity. Protein families were evolved using balanced and unbalanced trees, with ancient or recent radiations. In families sharing statistically significant similarity, about 60% of multiple sequence alignments were 95% identical to true alignments. To compare recovered topologies with true topologies, we used a score that reflects the fraction of clades that were correctly clustered. As expected, the accuracy of the phylogenies was greatest in the least divergent families. About 88% of phylogenies clustered over 80% of clades in families that shared significant sequence similarity, using Bayesian, parsimony, distance, and maximum likelihood methods. However, for protein families with short ancient branches (ancient radiation), only 30% of the most divergent (but statistically significant) families produced accurate phylogenies, and only about 70% of the second most highly conserved families, with median expectation values better than 10(-60), produced accurate trees. These values represent upper bounds on expected tree accuracy for sequences with a simple divergence history; proteins from 700 Giardia families, with a similar range of sequence similarities but considerably more gaps, produced much less accurate trees. For our simulated insertions and deletions, correct multiple sequence alignments did not perform much better than those produced by T-COFFEE, and including sequences with expressed sequence tag-like sequencing errors did not

Phylogenetic trees in bioinformatics

Energy Technology Data Exchange (ETDEWEB)

Burr, Tom L [Los Alamos National Laboratory

2008-01-01

Genetic data is often used to infer evolutionary relationships among a collection of viruses, bacteria, animal or plant species, or other operational taxonomic units (OTU). A phylogenetic tree depicts such relationships and provides a visual representation of the estimated branching order of the OTUs. Tree estimation is unique for several reasons, including: the types of data used to represent each OTU; the use ofprobabilistic nucleotide substitution models; the inference goals involving both tree topology and branch length, and the huge number of possible trees for a given sample of a very modest number of OTUs, which implies that fmding the best tree(s) to describe the genetic data for each OTU is computationally demanding. Bioinformatics is too large a field to review here. We focus on that aspect of bioinformatics that includes study of similarities in genetic data from multiple OTUs. Although research questions are diverse, a common underlying challenge is to estimate the evolutionary history of the OTUs. Therefore, this paper reviews the role of phylogenetic tree estimation in bioinformatics, available methods and software, and identifies areas for additional research and development.

Phylogenetic status of brown trout Salmo trutta populations in five rivers from the southern Caspian Sea and two inland lake basins, Iran: a morphogenetic approach.

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Hashemzadeh Segherloo, I; Farahmand, H; Abdoli, A; Bernatchez, L; Primmer, C R; Swatdipong, A; Karami, M; Khalili, B

2012-10-01

Interrelationships, origin and phylogenetic affinities of brown trout Salmo trutta populations from the southern Caspian Sea basin, Orumieh and Namak Lake basins in Iran were analysed from complete mtDNA control region sequences, 12 microsatellite loci and morphological characters. Among 129 specimens from six populations, seven haplotypes were observed. Based on mtDNA haplotype data, the Orumieh and southern Caspian populations did not differ significantly, but the Namak basin-Karaj population presented a unique haplotype closely related to the haplotypes of the other populations (0·1% Kimura two-parameter, K2P divergence). All Iranian haplotypes clustered as a distinct group within the Danube phylogenetic grouping, with an average K2P distance of 0·41% relative to other Danubian haplotypes. The Karaj haplotype in the Namak basin was related to a haplotype (Da26) formerly identified in the Tigris basin in Turkey, to a Salmo trutta oxianus haplotype from the Aral Sea basin, and to haplotype Da1a with two mutational steps, as well as to other Iranian haplotypes with one to two mutational steps, which may indicate a centre of origin in the Caspian basin. In contrast to results of the mtDNA analysis, more pronounced differentiation was observed among the populations studied in the morphological and microsatellite DNA data, except for the two populations from the Orumieh basin, which were similar, possibly due to anthropogenic causes. © 2012 The Authors. Journal of Fish Biology © 2012 The Fisheries Society of the British Isles.

Scanning probe lithography for nanoimprinting mould fabrication

International Nuclear Information System (INIS)

Luo Gang; Xie Guoyong; Zhang Yongyi; Zhang Guoming; Zhang Yingying; Carlberg, Patrick; Zhu Tao; Liu Zhongfan

2006-01-01

We propose a rational fabrication method for nanoimprinting moulds by scanning probe lithography. By wet chemical etching, different kinds of moulds are realized on Si(110) and Si(100) surfaces according to the Si crystalline orientation. The structures have line widths of about 200 nm with a high aspect ratio. By reactive ion etching, moulds with patterns free from the limitation of Si crystalline orientation are also obtained. With closed-loop scan control of a scanning probe microscope, the length of patterned lines is more than 100 μm by integrating several steps of patterning. The fabrication process is optimized in order to produce a mould pattern with a line width about 10 nm. The structures on the mould are further duplicated into PMMA resists through the nanoimprinting process. The method of combining scanning probe lithography with wet chemical etching or reactive ion etching (RIE) provides a resistless route for the fabrication of nanoimprinting moulds

Final report: Mapping Interactions in Hybrid Systems with Active Scanning Probes

Energy Technology Data Exchange (ETDEWEB)

Berezovsky, Jesse [Case Western Reserve Univ., Cleveland, OH (United States)

2017-09-29

This project aimed to study and map interactions between components of hybrid nanodevices using a novel scanning probe approach. To enable this work, we initially constructed a flexible experimental apparatus allowing for simultaneous scanning probe and confocal optical microscopy measurements. This setup was first used for all-optical measurements of nanostructures, with the focus then shifting to hybrid devices in which single coherent electron spins are coupled to micron-scale ferromagnetic elements, which may prove useful for addressing single spins, enhanced sensing, or spin-wave-mediated coupling of spins for quantum information applications. A significant breakthrough was the realization that it is not necessary to fabricate a magnetic structure on a scanning probe – instead a ferromagnetic vortex core can act as an integrated, solid state, scanning probe. The core of the vortex produces a very strong, localized fringe field which can be used analogously to an MFM tip. Unlike a traditional MFM tip, however, the vortex core is scanned within an integrated device (eliminating drift), and can be moved on vastly faster timescales. This approach allows the detailed investigation of interactions between single spins and complex driven ferromagnetic dynamics.

Functional morphology of the bovid astragalus in relation to habitat: controlling phylogenetic signal in ecomorphology.

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Barr, W Andrew

2014-11-01

Bovid astragali are one of the most commonly preserved bones in the fossil record. Accordingly, astragali are an important target for studies seeking to predict the habitat preferences of fossil bovids based on bony anatomy. However, previous work has not tested functional hypotheses linking astragalar morphology with habitat while controlling for body size and phylogenetic signal. This article presents a functional framework relating the morphology of the bovid astragalus to habitat-specific locomotor ecology and tests four hypotheses emanating from this framework. Highly cursorial bovids living in structurally open habitats are hypothesized to differ from their less cursorial closed-habitat dwelling relatives in having (1) relatively short astragali to maintain rotational speed throughout the camming motion of the rotating astragalus, (2) a greater range of angular excursion at the hock, (3) relatively larger joint surface areas, and (4) a more pronounced "spline-and-groove" morphology promoting lateral joint stability. A diverse sample of 181 astragali from 50 extant species was scanned using a Next Engine laser scanner. Species were assigned to one of four habitat categories based on the published ecological literature. A series of 11 linear measurements and three joint surface areas were measured on each astragalus. A geometric mean body size proxy was used to size-correct the measurement data. Phylogenetic generalized least squares (PGLS) was used to test for differences between habitat categories while controlling for body size differences and phylogenetic signal. Statistically significant PGLS results support Hypotheses 1 and 2 (which are not mutually exclusive) as well as Hypothesis 3. No support was found for Hypothesis 4. These findings confirm that the morphology of the bovid astragalus is related to habitat-specific locomotor ecology, and that this relationship is statistically significant after controlling for body size and phylogeny. Thus, this study

Efficient FPT Algorithms for (Strict) Compatibility of Unrooted Phylogenetic Trees.

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Baste, Julien; Paul, Christophe; Sau, Ignasi; Scornavacca, Celine

2017-04-01

In phylogenetics, a central problem is to infer the evolutionary relationships between a set of species X; these relationships are often depicted via a phylogenetic tree-a tree having its leaves labeled bijectively by elements of X and without degree-2 nodes-called the "species tree." One common approach for reconstructing a species tree consists in first constructing several phylogenetic trees from primary data (e.g., DNA sequences originating from some species in X), and then constructing a single phylogenetic tree maximizing the "concordance" with the input trees. The obtained tree is our estimation of the species tree and, when the input trees are defined on overlapping-but not identical-sets of labels, is called "supertree." In this paper, we focus on two problems that are central when combining phylogenetic trees into a supertree: the compatibility and the strict compatibility problems for unrooted phylogenetic trees. These problems are strongly related, respectively, to the notions of "containing as a minor" and "containing as a topological minor" in the graph community. Both problems are known to be fixed parameter tractable in the number of input trees k, by using their expressibility in monadic second-order logic and a reduction to graphs of bounded treewidth. Motivated by the fact that the dependency on k of these algorithms is prohibitively large, we give the first explicit dynamic programming algorithms for solving these problems, both running in time [Formula: see text], where n is the total size of the input.

PhyloSift: phylogenetic analysis of genomes and metagenomes.

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Darling, Aaron E; Jospin, Guillaume; Lowe, Eric; Matsen, Frederick A; Bik, Holly M; Eisen, Jonathan A

2014-01-01

Like all organisms on the planet, environmental microbes are subject to the forces of molecular evolution. Metagenomic sequencing provides a means to access the DNA sequence of uncultured microbes. By combining DNA sequencing of microbial communities with evolutionary modeling and phylogenetic analysis we might obtain new insights into microbiology and also provide a basis for practical tools such as forensic pathogen detection. In this work we present an approach to leverage phylogenetic analysis of metagenomic sequence data to conduct several types of analysis. First, we present a method to conduct phylogeny-driven Bayesian hypothesis tests for the presence of an organism in a sample. Second, we present a means to compare community structure across a collection of many samples and develop direct associations between the abundance of certain organisms and sample metadata. Third, we apply new tools to analyze the phylogenetic diversity of microbial communities and again demonstrate how this can be associated to sample metadata. These analyses are implemented in an open source software pipeline called PhyloSift. As a pipeline, PhyloSift incorporates several other programs including LAST, HMMER, and pplacer to automate phylogenetic analysis of protein coding and RNA sequences in metagenomic datasets generated by modern sequencing platforms (e.g., Illumina, 454).

PhyloSift: phylogenetic analysis of genomes and metagenomes

Directory of Open Access Journals (Sweden)

Aaron E. Darling

2014-01-01

Full Text Available Like all organisms on the planet, environmental microbes are subject to the forces of molecular evolution. Metagenomic sequencing provides a means to access the DNA sequence of uncultured microbes. By combining DNA sequencing of microbial communities with evolutionary modeling and phylogenetic analysis we might obtain new insights into microbiology and also provide a basis for practical tools such as forensic pathogen detection.In this work we present an approach to leverage phylogenetic analysis of metagenomic sequence data to conduct several types of analysis. First, we present a method to conduct phylogeny-driven Bayesian hypothesis tests for the presence of an organism in a sample. Second, we present a means to compare community structure across a collection of many samples and develop direct associations between the abundance of certain organisms and sample metadata. Third, we apply new tools to analyze the phylogenetic diversity of microbial communities and again demonstrate how this can be associated to sample metadata.These analyses are implemented in an open source software pipeline called PhyloSift. As a pipeline, PhyloSift incorporates several other programs including LAST, HMMER, and pplacer to automate phylogenetic analysis of protein coding and RNA sequences in metagenomic datasets generated by modern sequencing platforms (e.g., Illumina, 454.

Long-branch attraction bias and inconsistency in Bayesian phylogenetics.

Science.gov (United States)

Kolaczkowski, Bryan; Thornton, Joseph W

2009-12-09

Bayesian inference (BI) of phylogenetic relationships uses the same probabilistic models of evolution as its precursor maximum likelihood (ML), so BI has generally been assumed to share ML's desirable statistical properties, such as largely unbiased inference of topology given an accurate model and increasingly reliable inferences as the amount of data increases. Here we show that BI, unlike ML, is biased in favor of topologies that group long branches together, even when the true model and prior distributions of evolutionary parameters over a group of phylogenies are known. Using experimental simulation studies and numerical and mathematical analyses, we show that this bias becomes more severe as more data are analyzed, causing BI to infer an incorrect tree as the maximum a posteriori phylogeny with asymptotically high support as sequence length approaches infinity. BI's long branch attraction bias is relatively weak when the true model is simple but becomes pronounced when sequence sites evolve heterogeneously, even when this complexity is incorporated in the model. This bias--which is apparent under both controlled simulation conditions and in analyses of empirical sequence data--also makes BI less efficient and less robust to the use of an incorrect evolutionary model than ML. Surprisingly, BI's bias is caused by one of the method's stated advantages--that it incorporates uncertainty about branch lengths by integrating over a distribution of possible values instead of estimating them from the data, as ML does. Our findings suggest that trees inferred using BI should be interpreted with caution and that ML may be a more reliable framework for modern phylogenetic analysis.

Novel TGM5 mutations in acral peeling skin syndrome.

Science.gov (United States)

van der Velden, Jaap J A J; van Geel, Michel; Nellen, Ruud G L; Jonkman, Marcel F; McGrath, John A; Nanda, Arti; Sprecher, Eli; van Steensel, Maurice A M; McLean, W H Irwin; Cassidy, Andrew J

2015-04-01

Acral peeling skin syndrome (APSS, MIM #609796) is a rare autosomal recessive disorder characterized by superficial exfoliation and blistering of the volar and dorsal aspects of hands and feet. The level of separation is at the junction of the stratum granulosum and stratum corneum. APSS is caused by mutations in the TGM5 gene encoding transglutaminase-5, which is important for structural integrity of the outermost epidermal layers. The majority of patients originate from Europe and carry a p.(Gly113Cys) mutation in TGM5. In this study, we report both European and non-European families carrying other mutations in the TGM5 gene. In 5 patients, we found 3 novel mutations: c.1001+2_1001+3del, c.1171G>A and c.1498C>T. To confirm their pathogenicity, we performed functional analyses with a transglutaminase activity assay, determined alternative splicing by reverse-transcribed PCR analysis and used databases and in silico prediction tools. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Statistical assignment of DNA sequences using Bayesian phylogenetics

DEFF Research Database (Denmark)

Terkelsen, Kasper Munch; Boomsma, Wouter Krogh; Huelsenbeck, John P.

2008-01-01

We provide a new automated statistical method for DNA barcoding based on a Bayesian phylogenetic analysis. The method is based on automated database sequence retrieval, alignment, and phylogenetic analysis using a custom-built program for Bayesian phylogenetic analysis. We show on real data...... that the method outperforms Blast searches as a measure of confidence and can help eliminate 80% of all false assignment based on best Blast hit. However, the most important advance of the method is that it provides statistically meaningful measures of confidence. We apply the method to a re......-analysis of previously published ancient DNA data and show that, with high statistical confidence, most of the published sequences are in fact of Neanderthal origin. However, there are several cases of chimeric sequences that are comprised of a combination of both Neanderthal and modern human DNA....

Continental scale patterns and predictors of fern richness and phylogenetic diversity

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Nathalie eNagalingum

2015-04-01

Full Text Available Because ferns have a wide range of habitat preferences and are widely distributed, they are an ideal group for understanding how diversity is distributed. Here we examine fern diversity on a broad-scale using standard and corrected richness measures as well as phylogenetic indices; in addition we determine the environmental predictors of each diversity metric. Using the combined records of Australian herbaria, a dataset of over 60,000 records was obtained for 89 genera to infer richness. A phylogenetic tree of all the genera was constructed and combined with the herbarium records to obtain phylogenetic diversity patterns. A hotspot of both taxic and phylogenetic diversity occurs in the Wet Tropics of northeastern Australia. Although considerable diversity is distributed along the eastern coast, some important regions of diversity are identified only after sample-standardization of richness and through the phylogenetic metric. Of all of the metrics, annual precipitation was identified as the most explanatory variable, in part, in agreement with global and regional fern studies. Precipitation was combined with a different variable for each different metric. For corrected richness, precipitation is combined with temperature seasonality, while correlation of phylogenetic diversity to precipitation plus radiation indicates support for the species-energy hypothesis. Significantly high and significantly low phylogenetic diversity were found in geographically separate areas. These areas are correlated with different climatic conditions such as seasonality in precipitation. The use of phylogenetic metrics identifies additional areas of significant diversity, some of which have not been revealed using traditional taxonomic analyses, suggesting that different ecological and evolutionary processes have operated over the continent. Our study demonstrates that it is possible and vital to incorporate evolutionary metrics when inferring biodiversity hotspots

Permanent magnet finger-size scanning electron microscope columns

Energy Technology Data Exchange (ETDEWEB)

Nelliyan, K., E-mail: elenk@nus.edu.sg [Department of Electrical and Computer Engineering, National University of Singapore, 4 Engineering Drive 3, Singapore 117576 (Singapore); Khursheed, A. [Department of Electrical and Computer Engineering, National University of Singapore, 4 Engineering Drive 3, Singapore 117576 (Singapore)

2011-07-21

This paper presents permanent magnet scanning electron microscope (SEM) designs for both tungsten and field emission guns. Each column makes use of permanent magnet technology and operates at a fixed primary beam voltage. A prototype column operating at a beam voltage of 15 kV was made and tested inside the specimen chamber of a conventional SEM. A small electrostatic stigmator unit and dedicated scanning coils were integrated into the column. The scan coils were wound directly around the objective lens iron core in order to reduce its size. Preliminary experimental images of a test grid specimen were obtained through the prototype finger-size column, demonstrating that it is in principle feasible.

Permanent magnet finger-size scanning electron microscope columns

International Nuclear Information System (INIS)

Nelliyan, K.; Khursheed, A.

2011-01-01

This paper presents permanent magnet scanning electron microscope (SEM) designs for both tungsten and field emission guns. Each column makes use of permanent magnet technology and operates at a fixed primary beam voltage. A prototype column operating at a beam voltage of 15 kV was made and tested inside the specimen chamber of a conventional SEM. A small electrostatic stigmator unit and dedicated scanning coils were integrated into the column. The scan coils were wound directly around the objective lens iron core in order to reduce its size. Preliminary experimental images of a test grid specimen were obtained through the prototype finger-size column, demonstrating that it is in principle feasible.

VC and ACIS/HOOPS based semi-physical virtual prototype design and motion simulation of 2D scanning mirror

Science.gov (United States)

Liu, Xiangyan; Dai, Xiaobing; He, Xudong; Gao, Pengcheng

2013-10-01

Image-spectrum integrated instrument is an infrared scanning system which integrates optics, mechanics, electrics and information processing. Not only can it achieve scene imaging, but also it can detect, track and identify targets of interests in the scene through acquiring their spectra. After having a brief introduction to image-spectrum integrated instrument and analyzing how 2D scanning mirror works, this paper built 3D model of 2D scanning mirror and simulated its motion using two PCs basing on VC++ and ACIS/HOOPS. Two PCs communicate with each other through serial ports. One PC serves as host computer, on which controlling software runs, is responsible for loading image sequence, image processing, target detecting, and generating and sending motion commands to scanning mirror. The other serves as slave computer, on which scanning mirror motion simulation software runs, is responsible for receiving motion commands to control scanning mirror to finish corresponding movements. This method proposed in this paper adopted semi-physical virtual prototype technology and used real scene image sequence to control virtual 2D scanning mirror and simulates motion of real 2D scanning mirror. It has no need for real scanning mirror and is of important practical significance for debugging controlling software of 2D scanning mirror.

KRAS mutation: should we test for it, and does it matter?

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Roberts, Patrick J; Stinchcombe, Thomas E

2013-03-10

Lung cancer is the leading cause of cancer mortality in the United States and worldwide. Previously, lung cancer was simplistically divided into non-small-cell lung cancer (NSCLC) and small-cell lung cancer. However, in the last decade, we have gone from a simplistic binary system of classifying lung cancer to defining NSCLC on the basis of molecular subsets. KRAS mutations represent the most common molecular change in NSCLC. The presence of KRAS mutation has been shown to be associated with a poor prognosis in NSCLC, but this is of little clinical utility. More important is determining the clinical utility of KRAS mutational analysis for predicting benefit of chemotherapy, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), anti-EGFR monoclonal antibodies, or other novel therapeutics. Current data does not support the routine use of KRAS mutational analysis for predicting chemotherapy benefit. Additionally, there was significant interest in using KRAS status to select patients for EGFR TKI and anti-EGFR monoclonal antibodies. However, the EGFR mutational status has demonstrated significant predictive value in the selection of patients for EGFR TKI therapy and is now the preferred test. An association between KRAS mutational status and benefit of anti-EGFR monoclonal antibodies has not been demonstrated in NSCLC. Here we review, in the context of NSCLC, the underlying biology of KRAS mutations, the predictive value of KRAS mutations for therapeutic intervention, and the integration of KRAS mutational testing into our current clinical paradigms.

Fast algorithms for computing phylogenetic divergence time.

Science.gov (United States)

Crosby, Ralph W; Williams, Tiffani L

2017-12-06

The inference of species divergence time is a key step in most phylogenetic studies. Methods have been available for the last ten years to perform the inference, but the performance of the methods does not yet scale well to studies with hundreds of taxa and thousands of DNA base pairs. For example a study of 349 primate taxa was estimated to require over 9 months of processing time. In this work, we present a new algorithm, AncestralAge, that significantly improves the performance of the divergence time process. As part of AncestralAge, we demonstrate a new method for the computation of phylogenetic likelihood and our experiments show a 90% improvement in likelihood computation time on the aforementioned dataset of 349 primates taxa with over 60,000 DNA base pairs. Additionally, we show that our new method for the computation of the Bayesian prior on node ages reduces the running time for this computation on the 349 taxa dataset by 99%. Through the use of these new algorithms we open up the ability to perform divergence time inference on large phylogenetic studies.

Mutation Spectrum and Phenotypic Features in Noonan Syndrome with PTPN11 Mutations: Definition of Two Novel Mutations.

Science.gov (United States)

Atik, Tahir; Aykut, Ayca; Hazan, Filiz; Onay, Huseyin; Goksen, Damla; Darcan, Sukran; Tukun, Ajlan; Ozkinay, Ferda

2016-06-01

To evaluate the spectrum of PTPN11 gene mutations in Noonan syndrome patients and to study the genotype-phenotype associations. In this study, twenty Noonan syndrome patients with PTPN11 mutations were included. The patients underwent a detailed clinical and physical evaluation. To identify inherited cases, parents of all mutation positive patients were analyzed. Thirteen different PTPN11 mutations, two of them being novel, were detected in the study group. These mutations included eleven missense mutations: p.G60A, p.D61N, p.Y62D, p.Y63C, p.E69Q, p.Q79R, p.Y279C,p.N308D, p.N308S, p.M504V, p.Q510R and two novel missense mutations: p.I56V and p.I282M. The frequency of cardiac abnormalities and short stature were found to be 80 % and 80 %, respectively. Mental retardation was not observed in patients having exon 8 mutations. No significant correlations were detected between other phenotypic features and genotypes. By identifying genotype-phenotype correlations, this study provides information on phenotypes observed in NS patients with different PTPN11 mutations.

A new ultrasensitive scanning calorimeter.

Science.gov (United States)

Plotnikov, V V; Brandts, J M; Lin, L N; Brandts, J F

1997-08-01

A new ultrasensitive differential scanning calorimeter is described, having a number of novel features arising from integration between hardware and software. It is capable of high performance in either a scanning or isothermal mode of operation. Upscanning is carried out adiabatically while downscanning is nonadiabatic. By using software-controlled signals sent continuously to appropriate hardware devices, it is possible to improve adiabaticity and constancy of scan rate through use of empirical prerun information stored in memory rather than by using feedback systems which respond in real time and generate thermal noise. Also, instrument response time is software-selectable, maximizing performance for both slow- and fast-transient systems. While these and other sophisticated functionalities have been introduced into the instrument to improve performance and data analysis, they are virtually invisible and add no additional complexities into operation of the instrument. Noise and baseline repeatability are an order of magnitude better than published raw data from other instruments so that high-quality results can be obtained on protein solutions, for example, using as little as 50 microg of protein in the sample cell.

High Resolution Melting (HRM) analysis for mutation screening of RGSL1,RGS16 and RGS8 in breast cancer

DEFF Research Database (Denmark)

Wiechec, Emilia; Wiuf, Carsten Henrik; Overgaard, Jens

2011-01-01

coding exons of RGSL1, RGS16, and RGS8 in tumors from 200 breast cancer patients. All sequence variants detected by HRM resulted in abnormal shape of the melting curves. The identified mutations and known single nucleotide polymorphisms (SNP) were subsequently confirmed by sequencing, and distribution...... cancer patients. In addition, a total of seven known SNPs were identified in this study. Genotype distributions were not significantly different between breast cancer patients and controls. CONCLUSIONS AND IMPACT: Identification of novel mutations within RGSL1 provides a new insight...... into the pathophysiology of breast cancer. Moreover, the HRM analysis represents a reliable and highly sensitive method for mutation scanning of multiple exons....

Phylogenetics of neotropical Platymiscium (Leguminosae

DEFF Research Database (Denmark)

Saslis-Lagoudakis, C. Haris; Chase, Mark W; Robinson, Daniel N

2008-01-01

Platymiscium is a neotropical legume genus of forest trees in the Pterocarpus clade of the pantropical "dalbergioid" clade. It comprises 19 species (29 taxa), distributed from Mexico to southern Brazil. This study presents a molecular phylogenetic analysis of Platymiscium and allies inferred from...

Phylogenetic relationships among Maloideae species

Science.gov (United States)

The Maloideae is a highly diverse sub-family of the Rosaceae containing several agronomically important species (Malus sp. and Pyrus sp.) and their wild relatives. Previous phylogenetic work within the group has revealed extensive intergeneric hybridization and polyploidization. In order to develop...

Published sequences do not support transfer of oseltamivir resistance mutations from avian to human influenza A virus strains.

Science.gov (United States)

Norberg, Peter; Lindh, Magnus; Olofsson, Sigvard

2015-03-28

Tamiflu (oseltamivir phosphate ester, OE) is a widely used antiviral active against influenza A virus. Its active metabolite, oseltamivir carboxylate (OC), is chemically stable and secreted into wastewater treatment plants. OC contamination of natural habitats of waterfowl might induce OC resistance in influenza viruses persistently infecting waterfowl, and lead to transfer of OC-resistance from avian to human influenza. The aim of this study was to evaluate whether such has occurred. A genomics approach including phylogenetic analysis and probability calculations for homologous recombination was applied on altogether 19,755 neuraminidase (N1 and N2) genes from virus sampled in humans and birds, with and without resistance mutations. No evidence for transfer of OE resistance mutations from avian to human N genes was obtained, and events suggesting recombination between human and avian influenza virus variants could not be traced in the sequence material studied. The results indicate that resistance in influenza viruses infecting humans is due to the selection pressure posed by the global OE administration in humans rather than transfer from avian influenza A virus strains carrying mutations induced by environmental exposure to OC.

Scanning SQUID susceptometers with sub-micron spatial resolution

Energy Technology Data Exchange (ETDEWEB)

Kirtley, John R., E-mail: jkirtley@stanford.edu; Rosenberg, Aaron J.; Palmstrom, Johanna C.; Holland, Connor M.; Moler, Kathryn A. [Department of Applied Physics, Stanford University, Stanford, California 94305-4045 (United States); Paulius, Lisa [Department of Physics, Western Michigan University, Kalamazoo, Michigan 49008-5252 (United States); Spanton, Eric M. [Department of Physics, Stanford University, Stanford, California 94305-4045 (United States); Schiessl, Daniel [Attocube Systems AG, Königinstraße 11A, 80539 Munich (Germany); Jermain, Colin L.; Gibbons, Jonathan [Department of Physics, Cornell University, Cornell, Ithaca, New York 14853 (United States); Fung, Y.-K.K.; Gibson, Gerald W. [IBM Research Division, T. J. Watson Research Center, Yorktown Heights, New York 10598 (United States); Huber, Martin E. [Department of Physics, University of Colorado Denver, Denver, Colorado 80217-3364 (United States); Ralph, Daniel C. [Department of Physics, Cornell University, Cornell, Ithaca, New York 14853 (United States); Kavli Institute at Cornell, Ithaca, New York 14853 (United States); Ketchen, Mark B. [OcteVue, Hadley, Massachusetts 01035 (United States)

2016-09-15

Superconducting QUantum Interference Device (SQUID) microscopy has excellent magnetic field sensitivity, but suffers from modest spatial resolution when compared with other scanning probes. This spatial resolution is determined by both the size of the field sensitive area and the spacing between this area and the sample surface. In this paper we describe scanning SQUID susceptometers that achieve sub-micron spatial resolution while retaining a white noise floor flux sensitivity of ≈2μΦ{sub 0}/Hz{sup 1/2}. This high spatial resolution is accomplished by deep sub-micron feature sizes, well shielded pickup loops fabricated using a planarized process, and a deep etch step that minimizes the spacing between the sample surface and the SQUID pickup loop. We describe the design, modeling, fabrication, and testing of these sensors. Although sub-micron spatial resolution has been achieved previously in scanning SQUID sensors, our sensors not only achieve high spatial resolution but also have integrated modulation coils for flux feedback, integrated field coils for susceptibility measurements, and batch processing. They are therefore a generally applicable tool for imaging sample magnetization, currents, and susceptibilities with higher spatial resolution than previous susceptometers.

Scanning SQUID susceptometers with sub-micron spatial resolution

International Nuclear Information System (INIS)

Kirtley, John R.; Rosenberg, Aaron J.; Palmstrom, Johanna C.; Holland, Connor M.; Moler, Kathryn A.; Paulius, Lisa; Spanton, Eric M.; Schiessl, Daniel; Jermain, Colin L.; Gibbons, Jonathan; Fung, Y.-K.K.; Gibson, Gerald W.; Huber, Martin E.; Ralph, Daniel C.; Ketchen, Mark B.

2016-01-01

Superconducting QUantum Interference Device (SQUID) microscopy has excellent magnetic field sensitivity, but suffers from modest spatial resolution when compared with other scanning probes. This spatial resolution is determined by both the size of the field sensitive area and the spacing between this area and the sample surface. In this paper we describe scanning SQUID susceptometers that achieve sub-micron spatial resolution while retaining a white noise floor flux sensitivity of ≈2μΦ_0/Hz"1"/"2. This high spatial resolution is accomplished by deep sub-micron feature sizes, well shielded pickup loops fabricated using a planarized process, and a deep etch step that minimizes the spacing between the sample surface and the SQUID pickup loop. We describe the design, modeling, fabrication, and testing of these sensors. Although sub-micron spatial resolution has been achieved previously in scanning SQUID sensors, our sensors not only achieve high spatial resolution but also have integrated modulation coils for flux feedback, integrated field coils for susceptibility measurements, and batch processing. They are therefore a generally applicable tool for imaging sample magnetization, currents, and susceptibilities with higher spatial resolution than previous susceptometers.