James Taylor

Publications of James Taylor

• Making whole genome multiple alignments usable for biologists.

  Authors: Daniel Blankenberg, James Taylor, Anton Nekrutenko

  Bioinformatics (Oxford, England). 09/2011; 27(17):2426-8.

  Here we describe a set of tools implemented within the Galaxy platform designed to make analysis of multiple genome alignments truly accessible for biologists. These tools are available through bothHere we describe a set of tools implemented within the Galaxy platform designed to make analysis of multiple genome alignments truly accessible for biologists. These tools are available through both a web-based graphical user interface and a command-line interface. AVAILABILITY AND IMPLEMENTATION: This open-source toolset was implemented in Python and has been integrated into the online data analysis platform Galaxy (public web access: http://usegalaxy.org; download: http://getgalaxy.org). Additional help is available as a live supplement from http://usegalaxy.org/u/dan/p/maf. james.taylor@emory.edu; anton@bx.psu.edu Supplementary data are available at Bioinformatics online.

• Dynamics of the epigenetic landscape during erythroid differentiation after GATA1 restoration.

  Authors: Weisheng Wu, Yong Cheng, Cheryl A Keller, Jason Ernst, Swathi Ashok Kumar, Tejaswini Mishra, Christapher Morrissey, Christine M Dorman, Kuan-Bei Chen, Daniela Drautz [......] Terrence S Furey, Manolis Kellis, Webb Miller, James Taylor, Stephan C Schuster, Yu Zhang, Francesca Chiaromonte, Gerd A Blobel, Mitchell J Weiss, Ross C Hardison

  Genome research. 07/2011; 21(10):1659-71.

  Interplays among lineage-specific nuclear proteins, chromatin modifying enzymes, and the basal transcription machinery govern cellular differentiation, but their dynamics of action and coordinationInterplays among lineage-specific nuclear proteins, chromatin modifying enzymes, and the basal transcription machinery govern cellular differentiation, but their dynamics of action and coordination with transcriptional control are not fully understood. Alterations in chromatin structure appear to establish a permissive state for gene activation at some loci, but they play an integral role in activation at other loci. To determine the predominant roles of chromatin states and factor occupancy in directing gene regulation during differentiation, we mapped chromatin accessibility, histone modifications, and nuclear factor occupancy genome-wide during mouse erythroid differentiation dependent on the master regulatory transcription factor GATA1. Notably, despite extensive changes in gene expression, the chromatin state profiles (proportions of a gene in a chromatin state dominated by activating or repressive histone modifications) and accessibility remain largely unchanged during GATA1-induced erythroid differentiation. In contrast, gene induction and repression are strongly associated with changes in patterns of transcription factor occupancy. Our results indicate that during erythroid differentiation, the broad features of chromatin states are established at the stage of lineage commitment, largely independently of GATA1. These determine permissiveness for expression, with subsequent induction or repression mediated by distinctive combinations of transcription factors.

• Dynamics of mitochondrial heteroplasmy in three families investigated via a repeatable re-sequencing study.

  Authors: Hiroki Goto, Benjamin Dickins, Enis Afgan, Ian M Paul, James Taylor, Kateryna D Makova, Anton Nekrutenko

  Genome biology. 06/2011; 12(6):R59.

  ABSTRACT: BACKGROUND: Originally believed to be a rare phenomenon, heteroplasmy - the presence of more than one mitochondrial DNA (mtDNA) variant within a cell, tissue, or individual - is emerging asABSTRACT: BACKGROUND: Originally believed to be a rare phenomenon, heteroplasmy - the presence of more than one mitochondrial DNA (mtDNA) variant within a cell, tissue, or individual - is emerging as an important component of eukaryotic genetic diversity. Heteroplasmies can be used as genetic markers in applications ranging from forensics to cancer diagnostics. Yet the frequency of heteroplasmic alleles may vary from generation to generation due to the bottleneck occurring during oogenesis. Therefore, to understand the alterations in allele frequencies at heteroplasmic sites, it is of critical importance to investigate the dynamics of maternal mtDNA transmission. RESULTS: Here we sequenced, at high coverage, mtDNA from blood and buccal tissues of nine individuals from three families with a total of six maternal transmission events. Using simulations and re-sequencing of clonal DNA, we devised a set of criteria for detecting polymorphic sites in heterogeneous genetic samples that is resistant to the noise originating from massively parallel sequencing technologies. Application of these criteria to nine human mtDNA samples revealed four heteroplasmic sites. CONCLUSIONS: Our results suggest that the incidence of heteroplasmy may be lower than estimated in some other recent re-sequencing studies, and that mtDNA allelic frequencies differ significantly both between tissues of the same individual and between a mother and her offspring. We designed our study in such a way that the complete analysis described here can be repeated by anyone either at our site or directly on the Amazon Cloud. Our computational pipeline can be easily modified to accommodate other applications, such as viral re-sequencing.

• Making whole genome multiple alignments usable for biologists.

  Authors: Daniel Blankenberg, James Taylor, Anton Nekrutenko, The Galaxy Team

  Bioinformatics. 01/2011; 27:2426-2428.

• Harnessing cloud computing with Galaxy Cloud.

  Authors: Enis Afgan, Dannon Baker, Nate Coraor, Hiroki Goto, Ian M Paul, Kateryna D Makova, Anton Nekrutenko, James Taylor

  Nature biotechnology. 01/2011; 29(11):972-4.

• Integrating diverse databases into an unified analysis framework: a Galaxy approach.

  Authors: Daniel Blankenberg, Nathan Coraor, Gregory Von Kuster, James Taylor, Anton Nekrutenko

  Database : the journal of biological databases and curation. 01/2011; 2011:bar011.

  Recent technological advances have lead to the ability to generate large amounts of data for model and non-model organisms. Whereas, in the past, there have been a relatively small number of centralRecent technological advances have lead to the ability to generate large amounts of data for model and non-model organisms. Whereas, in the past, there have been a relatively small number of central repositories that serve genomic data, an increasing number of distinct specialized data repositories and resources have been established. Here, we describe a generic approach that provides for the integration of a diverse spectrum of data resources into a unified analysis framework, Galaxy (http://usegalaxy.org). This approach allows the simplified coupling of external data resources with the data analysis tools available to Galaxy users, while leveraging the native data mining facilities of the external data resources. DATABASE URL: http://usegalaxy.org.

• The genome sequence of the leaf-cutter ant Atta cephalotes reveals insights into its obligate symbiotic lifestyle.

  Authors: Garret Suen, Clotilde Teiling, Lewyn Li, Carson Holt, Ehab Abouheif, Erich Bornberg-Bauer, Pascal Bouffard, Eric J Caldera, Elizabeth Cash, Amy Cavanaugh [......] Fabian Zimmer, James Taylor, Steven C Slater, Sandra W Clifton, Wesley C Warren, Christine G Elsik, Christopher D Smith, George M Weinstock, Nicole M Gerardo, Cameron R Currie

  PLoS genetics. 01/2011; 7(2):e1002007.

  Leaf-cutter ants are one of the most important herbivorous insects in the Neotropics, harvesting vast quantities of fresh leaf material. The ants use leaves to cultivate a fungus that serves as theLeaf-cutter ants are one of the most important herbivorous insects in the Neotropics, harvesting vast quantities of fresh leaf material. The ants use leaves to cultivate a fungus that serves as the colony's primary food source. This obligate ant-fungus mutualism is one of the few occurrences of farming by non-humans and likely facilitated the formation of their massive colonies. Mature leaf-cutter ant colonies contain millions of workers ranging in size from small garden tenders to large soldiers, resulting in one of the most complex polymorphic caste systems within ants. To begin uncovering the genomic underpinnings of this system, we sequenced the genome of Atta cephalotes using 454 pyrosequencing. One prediction from this ant's lifestyle is that it has undergone genetic modifications that reflect its obligate dependence on the fungus for nutrients. Analysis of this genome sequence is consistent with this hypothesis, as we find evidence for reductions in genes related to nutrient acquisition. These include extensive reductions in serine proteases (which are likely unnecessary because proteolysis is not a primary mechanism used to process nutrients obtained from the fungus), a loss of genes involved in arginine biosynthesis (suggesting that this amino acid is obtained from the fungus), and the absence of a hexamerin (which sequesters amino acids during larval development in other insects). Following recent reports of genome sequences from other insects that engage in symbioses with beneficial microbes, the A. cephalotes genome provides new insights into the symbiotic lifestyle of this ant and advances our understanding of host-microbe symbioses.

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• Manipulation of FASTQ data with Galaxy.

  Authors: Daniel Blankenberg, Assaf Gordon, Gregory Von Kuster, Nathan Coraor, James Taylor, Anton Nekrutenko

  Bioinformatics (Oxford, England). 07/2010; 26(14):1783-5.

  SUMMARY: Here, we describe a tool suite that functions on all of the commonly known FASTQ format variants and provides a pipeline for manipulating next generation sequencing data taken from aSUMMARY: Here, we describe a tool suite that functions on all of the commonly known FASTQ format variants and provides a pipeline for manipulating next generation sequencing data taken from a sequencing machine all the way through the quality filtering steps. Availability and Implementation: This open-source toolset was implemented in Python and has been integrated into the online data analysis platform Galaxy (public web access: http://usegalaxy.org; download: http://getgalaxy.org). Two short movies that highlight the functionality of tools described in this manuscript as well as results from testing components of this tool suite against a set of previously published files are available at http://usegalaxy.org/u/dan/p/fastq

• Galaxy: a web-based genome analysis tool for experimentalists.

  Authors: Daniel Blankenberg, Gregory Von Kuster, Nathaniel Coraor, Guruprasad Ananda, Ross Lazarus, Mary Mangan, Anton Nekrutenko, James Taylor

  Current protocols in molecular biology / edited by Frederick M. Ausubel ... [et al.]. 01/2010; Chapter 19:Unit 19.10.1-21.

  High-throughput data production has revolutionized molecular biology. However, massive increases in data generation capacity require analysis approaches that are more sophisticated, and often veryHigh-throughput data production has revolutionized molecular biology. However, massive increases in data generation capacity require analysis approaches that are more sophisticated, and often very computationally intensive. Thus, making sense of high-throughput data requires informatics support. Galaxy (http://galaxyproject.org) is a software system that provides this support through a framework that gives experimentalists simple interfaces to powerful tools, while automatically managing the computational details. Galaxy is distributed both as a publicly available Web service, which provides tools for the analysis of genomic, comparative genomic, and functional genomic data, or a downloadable package that can be deployed in individual laboratories. Either way, it allows experimentalists without informatics or programming expertise to perform complex large-scale analysis with just a Web browser.

• Galaxy CloudMan: delivering cloud compute clusters.

  Authors: Enis Afgan, Dannon Baker, Nate Coraor, Brad Chapman, Anton Nekrutenko, James Taylor

  BMC bioinformatics. 01/2010; 11 Suppl 12:S4.

  Widespread adoption of high-throughput sequencing has greatly increased the scale and sophistication of computational infrastructure needed to perform genomic research. An alternative to building andWidespread adoption of high-throughput sequencing has greatly increased the scale and sophistication of computational infrastructure needed to perform genomic research. An alternative to building and maintaining local infrastructure is "cloud computing", which, in principle, offers on demand access to flexible computational infrastructure. However, cloud computing resources are not yet suitable for immediate "as is" use by experimental biologists. We present a cloud resource management system that makes it possible for individual researchers to compose and control an arbitrarily sized compute cluster on Amazon's EC2 cloud infrastructure without any informatics requirements. Within this system, an entire suite of biological tools packaged by the NERC Bio-Linux team (http://nebc.nerc.ac.uk/tools/bio-linux) is available for immediate consumption. The provided solution makes it possible, using only a web browser, to create a completely configured compute cluster ready to perform analysis in less than five minutes. Moreover, we provide an automated method for building custom deployments of cloud resources. This approach promotes reproducibility of results and, if desired, allows individuals and labs to add or customize an otherwise available cloud system to better meet their needs. The expected knowledge and associated effort with deploying a compute cluster in the Amazon EC2 cloud is not trivial. The solution presented in this paper eliminates these barriers, making it possible for researchers to deploy exactly the amount of computing power they need, combined with a wealth of existing analysis software, to handle the ongoing data deluge.

• Web-based analysis of (Epi-) genome data using EpiGRAPH and Galaxy.

  Authors: Christoph Bock, Greg Von Kuster, Konstantin Halachev, James Taylor, Anton Nekrutenko, Thomas Lengauer

  Methods in molecular biology (Clifton, N.J.). 01/2010; 628:275-96.

  Modern life sciences are becoming increasingly data intensive, posing a significant challenge for most researchers and shifting the bottleneck of scientific discovery from data generation to dataModern life sciences are becoming increasingly data intensive, posing a significant challenge for most researchers and shifting the bottleneck of scientific discovery from data generation to data analysis. As a result, progress in genome research is increasingly impeded by bioinformatic hurdles. A new generation of powerful and easy-to-use genome analysis tools has been developed to address this issue, enabling biologists to perform complex bioinformatic analyses online - without having to learn a programming language or downloading and manually processing large datasets. In this tutorial paper, we describe the use of EpiGRAPH (http://epigraph.mpi-inf.mpg.de/) and Galaxy (http://galaxyproject.org/) for genome and epigenome analysis, and we illustrate how these two web services work together to identify epigenetic modifications that are characteristics of highly polymorphic (SNP-rich) promoters. This paper is supplemented with video tutorials (http://tinyurl.com/yc5xkqq), which provide a step-by-step guide through each example analysis.

• Windshield splatter analysis with the Galaxy metagenomic pipeline.

  Authors: Sergei Kosakovsky Pond, Samir Wadhawan, Francesca Chiaromonte, Guruprasad Ananda, Wen-Yu Chung, James Taylor, Anton Nekrutenko

  Genome research. 10/2009;

  How many species inhabit our immediate surroundings? A straightforward collection technique suitable for answering this question is known to anyone who has ever driven a car at highway speeds. TheHow many species inhabit our immediate surroundings? A straightforward collection technique suitable for answering this question is known to anyone who has ever driven a car at highway speeds. The windshield of a moving vehicle is subjected to numerous insect strikes and can be used as a collection device for representative sampling. Unfortunately the analysis of biological material collected in that manner, as with most metagenomic studies, proves to be rather demanding due to the large number of required tools and considerable computational infrastructure. In this study, we use organic matter collected by a moving vehicle to design and test a comprehensive pipeline for phylogenetic profiling of metagenomic samples that includes all steps from processing and quality control of data generated by next-generation sequencing technologies to statistical analyses and data visualization. To the best of our knowledge, this is also the first publication that features a live online supplement providing access to exact analyses and workflows used in the article.

• Primary sequence and epigenetic determinants of in vivo occupancy of genomic DNA by GATA1.

  Authors: Ying Zhang, Weisheng Wu, Yong Cheng, David C King, Robert S Harris, James Taylor, Francesca Chiaromonte, Ross C Hardison

  Nucleic acids research. 09/2009;

  DNA sequence motifs and epigenetic modifications contribute to specific binding by a transcription factor, but the extent to which each feature determines occupancy in vivo is poorly understood. WeDNA sequence motifs and epigenetic modifications contribute to specific binding by a transcription factor, but the extent to which each feature determines occupancy in vivo is poorly understood. We addressed this question in erythroid cells by identifying DNA segments occupied by GATA1 and measuring the level of trimethylation of histone H3 lysine 27 (H3K27me3) and monomethylation of H3 lysine 4 (H3K4me1) along a 66 Mb region of mouse chromosome 7. While 91% of the GATA1-occupied segments contain the consensus binding-site motif WGATAR, only approximately 0.7% of DNA segments with such a motif are occupied. Using a discriminative motif enumeration method, we identified additional motifs predictive of occupancy given the presence of WGATAR. The specific motif variant AGATAA and occurrence of multiple WGATAR motifs are both strong discriminators. Combining motifs to pair a WGATAR motif with a binding site motif for GATA1, EKLF or SP1 improves discriminative power. Epigenetic modifications are also strong determinants, with the factor-bound segments highly enriched for H3K4me1 and depleted of H3K27me3. Combining primary sequence and epigenetic determinants captures 52% of the GATA1-occupied DNA segments and substantially increases the specificity, to one out of seven segments with the required motif combination and epigenetic signals being bound.

• Genome analysis of the platypus reveals unique signatures of evolution.

  Authors: Wesley C Warren, Ladeana W Hillier, Jennifer A Marshall Graves, Ewan Birney, Chris P Ponting, Frank Grützner, Katherine Belov, Webb Miller, Laura Clarke, Asif T Chinwalla [......] Prathapan Thiru, Michael N Nhan, Craig S Pohl, Scott M Smith, Shunfeng Hou, Mikhail Nefedov, Pieter J de Jong, Marilyn B Renfree, Elaine R Mardis, Richard K Wilson

  Nature. 10/2008; 455(7210):256.

• Genome analysis of the platypus reveals unique signatures of evolution.

  Authors: Wesley C Warren, Ladeana W Hillier, Jennifer A Marshall Graves, Ewan Birney, Chris P Ponting, Frank Grützner, Katherine Belov, Webb Miller, Laura Clarke, Asif T Chinwalla [......] Todd Wylie, Patricia Wohldmann, Prathapan Thiru, Michael N Nhan, Craig S Pohl, Scott M Smith, Shunfeng Hou, Marilyn B Renfree, Elaine R Mardis, Richard K Wilson

  Nature. 06/2008; 453(7192):175-83.

  We present a draft genome sequence of the platypus, Ornithorhynchus anatinus. This monotreme exhibits a fascinating combination of reptilian and mammalian characters. For example, platypuses have aWe present a draft genome sequence of the platypus, Ornithorhynchus anatinus. This monotreme exhibits a fascinating combination of reptilian and mammalian characters. For example, platypuses have a coat of fur adapted to an aquatic lifestyle; platypus females lactate, yet lay eggs; and males are equipped with venom similar to that of reptiles. Analysis of the first monotreme genome aligned these features with genetic innovations. We find that reptile and platypus venom proteins have been co-opted independently from the same gene families; milk protein genes are conserved despite platypuses laying eggs; and immune gene family expansions are directly related to platypus biology. Expansions of protein, non-protein-coding RNA and microRNA families, as well as repeat elements, are identified. Sequencing of this genome now provides a valuable resource for deep mammalian comparative analyses, as well as for monotreme biology and conservation.

• Comparative analyses of bidirectional promoters in vertebrates.

  Authors: Mary Qu Yang, James Taylor, Laura Elnitski

  BMC bioinformatics. 02/2008; 9 Suppl 6:S9.

  BACKGROUND: Orthologous genes with deep phylogenetic histories are likely to retain similar regulatory features. In this report we utilize orthology assignments for pairs of genes co-regulated byBACKGROUND: Orthologous genes with deep phylogenetic histories are likely to retain similar regulatory features. In this report we utilize orthology assignments for pairs of genes co-regulated by bidirectional promoters to map the ancestral history of the promoter regions. RESULTS: Our mapping of bidirectional promoters from humans to fish shows that many such promoters emerged after the divergence of chickens and fish. Furthermore, annotations of promoters in deep phylogenies enable detection of missing data or assembly problems present in higher vertebrates. The functional importance of bidirectional promoters is indicated by selective pressure to maintain the arrangement of genes regulated by the promoter over long evolutionary time spans. Characteristics unique to bidirectional promoters are further elucidated using a technique for unsupervised classification, known as ESPERR. CONCLUSION: Results of these analyses will aid in our understanding of the evolution of bidirectional promoters, including whether the regulation of two genes evolved as a consequence of their proximity or if function dictated their co-regulation.

• Comparative analyses of bidirectional promoters in vertebrates.

  Authors: Mary Qu Yang, James Taylor, Laura Elnitski

  BMC Bioinformatics. 01/2008; 9.

• Phylogenomic resources at the UCSC Genome Browser.

  Authors: Kate Rosenbloom, James Taylor, Stephen Schaeffer, Jim Kent, David Haussler, Webb Miller

  Methods in molecular biology (Clifton, N.J.). 01/2008; 422:133-44.

  The UC Santa Cruz Genome Browser provides a number of resources that can be used for phylogenomic studies, including (1) whole-genome sequence data from a number of vertebrate species, (2) pairwiseThe UC Santa Cruz Genome Browser provides a number of resources that can be used for phylogenomic studies, including (1) whole-genome sequence data from a number of vertebrate species, (2) pairwise alignments of the human genome sequence to a number of other vertebrate genome, (3) a simultaneous alignment of 17 vertebrate genomes (most of them incompletely sequenced) that covers all of the human sequence, (4) several independent sets of multiple alignments covering 1% of the human genome (ENCODE regions), (5) extensive sequence annotation for interpreting those sequences and alignments, and (6) sequence, alignments, and annotations from certain other species, including an alignment of nine insect genomes. We illustrate the use of these resources in the context of assigning rare genomic changes to the branch of the phylogenetic tree where they appear to have occurred, or of looking for evidence supporting a particular possible tree topology. Sample source code for performing such studies is available.

• Toward the commoditization of translational genomic research: Design and implementation features of the Galaxy genomic workbench.

  Authors: Ross Lazarus, James Taylor, Weiliang Qiu, Anton Nekrutenko

  Summit on translational bioinformatics. 01/2008; 2008:56-60.

  Although there is now plenty of genomic data and no shortage of analysis methods for translational genomic research, many biologists do not have efficient and transparent access to the computationalAlthough there is now plenty of genomic data and no shortage of analysis methods for translational genomic research, many biologists do not have efficient and transparent access to the computational resources they need. No single data resource or analysis application is ever likely to efficiently address all aspects of any individual researcher's needs, so most researchers are forced to manually integrate data and outputs from multiple resources. The inevitable heterogeneity of data formats and of command syntax between data resources and software applications presents a major obstacle, particularly to those biologists lacking practical informatics skills. We describe some design and implementation features of an open-source application that supports the integration of the best available third-party genomics software applications, data and annotation resources into a coherent framework, substantially overcoming many practical challenges associated with actually doing translational genomic research.

• 28-way vertebrate alignment and conservation track in the UCSC Genome Browser.

  Authors: Webb Miller, Kate Rosenbloom, Ross C Hardison, Minmei Hou, James Taylor, Brian Raney, Richard Burhans, David C King, Robert Baertsch, Daniel Blankenberg [......] Thomas H Pringle, William J Murphy, Arthur Lesk, George M Weinstock, Kerstin Lindblad-Toh, Richard A Gibbs, Eric S Lander, Adam Siepel, David Haussler, W James Kent

  Genome research. 01/2008; 17(12):1797-808.

  This article describes a set of alignments of 28 vertebrate genome sequences that is provided by the UCSC Genome Browser. The alignments can be viewed on the Human Genome Browser (March 2006This article describes a set of alignments of 28 vertebrate genome sequences that is provided by the UCSC Genome Browser. The alignments can be viewed on the Human Genome Browser (March 2006 assembly) at http://genome.ucsc.edu, downloaded in bulk by anonymous FTP from http://hgdownload.cse.ucsc.edu/goldenPath/hg18/multiz28way, or analyzed with the Galaxy server at http://g2.bx.psu.edu. This article illustrates the power of this resource for exploring vertebrate and mammalian evolution, using three examples. First, we present several vignettes involving insertions and deletions within protein-coding regions, including a look at some human-specific indels. Then we study the extent to which start codons and stop codons in the human sequence are conserved in other species, showing that start codons are in general more poorly conserved than stop codons. Finally, an investigation of the phylogenetic depth of conservation for several classes of functional elements in the human genome reveals striking differences in the rates and modes of decay in alignability. Each functional class has a distinctive period of stringent constraint, followed by decays that allow (for the case of regulatory regions) or reject (for coding regions and ultraconserved elements) insertions and deletions.