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bioRxiv (pronounced "bio-archive") is a free online archive and distribution service for unpublished preprints in the life sciences. It is operated by Cold Spring Harbor Laboratory, a not-for-profit research and educational institution. By posting preprints on bioRxiv, authors are able to make their findings immediately available to the scientific community and receive feedback on draft manuscripts before they are submitted to journals.



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biorxiv
by Iosif Lazaridis; Nick Patterson; Alissa Mittnik; Gabriel Renaud; Swapan Mallick; Karola Kirsanow; Peter H. Sudmant; Joshua G. Schraiber; Sergi Castellano; Mark Lipson; Bonnie Berger; Tatijana Zemunik; Alan Cooper; Cristian Capelli; Mark G. Thomas; Andres Ruiz-Linares; Sarah A. Tishkoff; Lalji Singh; Kumarasamy Thangaraj; Richard Villems; David Comas; Christos Economou; Rem Sukernik; Mait Metspalu; Matthias Meyer; Evan E. Eichler; Joachim Burger; Montgomery Slatkin; Svante Pååbo; Janet Kelso;...
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We sequenced genomes from a ~7,000 year old early farmer from Stuttgart in Germany, an ~8,000 year old hunter-gatherer from Luxembourg, and seven ~8,000 year old hunter-gatherers from southern Sweden. We analyzed these data together with other ancient genomes and 2,345 contemporary humans to show that the great majority of present-day Europeans derive from at least three highly differentiated populations: West European Hunter-Gatherers (WHG), who contributed ancestry to all Europeans but not to...
Topic: Genetics
Source: http://biorxiv.org/content/early/2014/04/05/001552
biorxiv
by Christian L Althaus; Beda Joos; Alan S Perelson; Huldrych F Günthard
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Background: HIV-1-infected cells in peripheral blood can be grouped into different transcriptional subclasses. Quantifying the turnover of these cellular subclasses can provide important insights into the viral life cycle and the generation and maintenance of latently infected cells. Results: We used previously published data from five patients chronically infected with HIV-1 that initiated combination antiretroviral therapy (cART). Patient-matched PCR for unspliced and multiply spliced viral...
Topic: Systems Biology
Source: http://biorxiv.org/content/early/2014/01/18/000778
biorxiv
by Alex Graudenzi; Giulio Caravagna; Giovanni De Matteis; Marco Antoniotti
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Colorectal tumors originate and develop within intestinal crypts. Even though some of the essential phenomena that characterize crypt structure and dynamics have been effectively described in the past, the relation between the differentiation process and the overall crypt homeostasis is still partially understood. We here investigate this relation and other important biological phenomena by introducing a novel multiscale model that combines a morphological description of the crypt with a gene...
Topic: Systems Biology
Source: http://biorxiv.org/content/early/2013/11/25/000927
biorxiv
by Thaddeus R Cybulski; Joshua I Glaser; Adam H Marblestone; Bradley M Zamft; Edward S Boyden; George M Church; Konrad P Kording
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A central issue in neural recording is that of distinguishing the activities of many neurons. Here, we develop a framework, based on Fisher information, to quantify how separable a neuron's activity is from the activities of nearby neurons. We (1) apply this framework to model information flow and spatial distinguishability for several electrical and optical neural recording methods, (2) provide analytic expressions for information content, and (3) demonstrate potential applications of the...
Topic: Neuroscience
Source: http://biorxiv.org/content/early/2014/02/21/002923
biorxiv
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The debate over the ethnogenesis of Ashkenazi Jewry is longstanding, and has been hampered by a lack of Jewish historiographical work between the Biblical and the early Modern eras. Most historians, as well as geneticists, situate them as the descendants of Israelite tribes whose presence in Europe is owed to deportations during the Roman conquest of Palestine, as well as migration from Babylonia, and eventual settlement along the Rhine. By contrast, a few historians and other writers, most...
Topic: Genetics
Source: http://biorxiv.org/content/early/2013/12/12/001354
biorxiv
by Ilya Korsunsky; Daniele Ramazzotti; Giulio Caravagna; Bud Mishra
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Many applications in translational medicine require the understanding of how diseases progress through the accumulation of persistent events. Specialized Bayesian networks called monotonic progression networks offer a statistical framework for modeling this sort of phenomenon. Current machine learning tools to reconstruct Bayesian networks from data are powerful but not suited to progression models. We combine the technological advances in machine learning with a rigorous philosophical theory...
Topic: Bioinformatics
Source: http://biorxiv.org/content/early/2014/08/25/008326
biorxiv
by Helena Khaliullina; Mesut Bilgin; Julio L. Sampaio; Andrej Shevchenko; Suzanne Eaton
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Hedgehog proteins are lipid-modified secreted signaling molecules that regulate tissue development and homeostasis. Lipids contained in circulating lipoproteins repress the Hedgehog signaling pathway in the absence of Hedgehog ligand, but the identity of these lipids is unknown. Here, using biochemical fractionation and lipid mass spectrometry, we identify these inhibitory lipids as endocannabinoids. Endocannabinoids are present in lipoproteins of both flies and humans, and repress the pathway...
Topic: Developmental Biology
Source: http://biorxiv.org/content/early/2013/11/18/000570
biorxiv
by David A. Hughes; Nicole C. Rodney; Connie J. Mulligan
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DNA methylation variation has been implicated as a factor that influences inter-individual and inter-tissue phenotypic variation in numerous organisms and under various conditions. Here, using a unique collection of three tissues, derived from 24 mother-newborn dyads from war-torn Democratic Republic of Congo, we estimate how stress, heritability, tissue type and genomic/regulatory context influence genome-wide DNA methylation. We also evaluate if stress-associated variation may mediate an...
Topic: Genetics
Source: http://biorxiv.org/content/early/2014/01/31/002303
biorxiv
by Samuel Minot; Stephen D Turner; Krista L Ternus; Dana R Kadavy
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Next-generation sequencing is increasingly being used to study samples composed of mixtures of organisms, such as in clinical applications where the presence of a pathogen at very low abundance may be highly important. We present an analytical method (SIANN: Strain Identification by Alignment to Near Neighbors) specifically designed to rapidly detect a set of target organisms in mixed samples that achieves a high degree of species- and strain-specificity by aligning short sequence reads to the...
Topic: Bioinformatics
Source: http://biorxiv.org/content/early/2014/01/10/001727
biorxiv
by Johannes Kohl; Julian Ng; Sebastian Cachero; Michael-John Dolan; Ben Sutcliffe; Daniel Krüger; Shahar Frechter; Gregory SXE Jefferis
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Genetically encoded fluorescent proteins and immunostainings are widely used to detect cellular or sub-cellular structures in thick biological samples. However, each approach suffers from limitations, including low signal and limited spectral flexibility or slow speed, poor penetration and high background, respectively. Here we overcome these limitations by using transgenically expressed chemical tags for rapid, even and low-background labeling of thick biological tissues. We construct a...
Topic: Neuroscience
Source: http://biorxiv.org/content/early/2014/05/19/005298
biorxiv
by Wen-Yun Yang; Alexander Platt; Charleston Wen-Kai Chiang; Eleazar Eskin; John Novembre; Bogdan Pasaniuc
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Ancestry analysis from genetic data plays a critical role in studies of human disease and evolution. Recent work has introduced explicit models for the geographic distribution of genetic variation and has shown that such explicit models yield superior accuracy in ancestry inference over non-model-based methods. Here we extend such work to introduce a method that models admixture between ancestors from multiple sources across a geographic continuum. We devise efficient algorithms based on hidden...
Topic: Genetics
Source: http://biorxiv.org/content/early/2014/05/04/004713
biorxiv
by Russell B. Corbett-Detig; Daniel L. Hartl; Timothy B. Sackton
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The range of genetic diversity observed within natural populations is much more narrow than expected based on models of neutral molecular evolution. Although the increased efficacy of natural selection in larger populations has been invoked to explain this paradox, to date no tests of this hypothesis have been conducted. Here, we present an analysis of whole-genome polymorphism data and genetic maps from 39 species to estimate for each species the reduction in genetic variation attributable to...
Topic: Genomics
Source: http://biorxiv.org/content/early/2014/06/09/006122
biorxiv
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A DNA profile from the perpetrator does not reveal, per se, the circumstances by which it was transferred. Body fluid identification by mRNA profiling may allow extraction of contextual 'activity level' information from forensic samples. Here we describe the development of a prototype multiplex digital gene expression (DGE) method for forensic body fluid/tissue identification based upon solution hybridization of color-coded NanoString® probes to 23 tissue/body fluid specific mRNA targets. The...
Topic: Genomics
Source: http://biorxiv.org/content/early/2014/08/12/007898
biorxiv
by Keisha Dawn Carlson; Peter H Sudmant; Maximilian Oliver Press; Evan E Eichler; Jay Shendure; Christine Queitsch
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Abstract Short tandem repeats (STRs) are highly mutable genetic elements that often reside in functional genomic regions. The cumulative evidence of genetic studies on individual STRs suggests that STR variation profoundly affects phenotype and contributes to trait heritability. Despite recent advances in sequencing technology, STR variation has remained largely inaccessible across many individuals compared to single nucleotide variation or copy number variation. STR genotyping with short-read...
Topic: Genomics
Source: http://biorxiv.org/content/early/2014/07/28/007500
biorxiv
by Feng Zeng; Rui Jiang; Guoli Ji; Ting Chen
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The incorrect alignments are a severe problem in variant calling, and remain as a challenge computational issue in Bioinformatics field. Although there have been some methods utilizing the re-alignment approach to tackle the misalignments, a standalone re-alignment tool for long sequencing reads is lacking. Hence, we present a standalone tool to correct the misalignments, called ProbAlign. It can be integrated into the pipelines of not only variant calling but also other genomic applications....
Topic: Bioinformatics
Source: http://biorxiv.org/content/early/2014/09/02/008698
biorxiv
by Jonathan Rodenfels; Oksana Lavrynenko; Sophie Ayciriex; Julio L Sampaio; Andrej Shevchenko; Suzanne Eaton
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In Drosophila larvae, growth and developmental timing are regulated by nutrition in a tightly coordinated fashion. The networks that couple these processes are far from understood. Here, we show that the intestine responds to nutrient availability by regulating production of a circulating lipoprotein-associated form of the signaling protein Hedgehog (Hh). Levels of circulating Hh tune the rates of growth and developmental timing in a coordinated fashion. Circulating Hh signals to the fat body...
Topic: Developmental Biology
Source: http://biorxiv.org/content/early/2014/07/29/002626
biorxiv
by Luke Stoeckel; Kathleen A. Garrison; Satrajit S Ghosh; Paul Wighton; Colleen A. Hanlon; Jodi M. Gilman; Stephanie Greer; Nicholas B. Turk-Browne; Megan T. deBettencourt; Dustin Scheinost; Cameron Craddock; Todd Thompson; Vanessa Calderon; Clemens C. Bauer; Mark George; Hans C. Breiter; Susan Whitfield-Gabrieli; John D. Gabrieli; Stephen M. LaConte; Laurence M. Hirshberg; Judson A. Brewer; Michelle Hampson; Andre Van Der Kouwe; Sean Mackey; Anne E Evins
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While reducing the burden of brain disorders remains a top priority of organizations like the World Health Organization and National Institutes of Health (BRAIN, 2013), the development of novel, safe and effective treatments for brain disorders has been slow. In this paper, we describe the state of the science for an emerging technology, real time functional magnetic resonance imaging (rtfMRI) neurofeedback, in clinical neurotherapeutics. We review the scientific potential of rtfMRI and outline...
Topic: Neuroscience
Source: http://biorxiv.org/content/early/2014/06/20/003400
biorxiv
by Ashley P Ng; Maria Kauppi; Donald Metcalf; Craig D Hyland; Emma C Josefsson; Marion Lebois; Jian-Guo Zhang; Ladina Di Rago; Tracey Baldwin; Douglas J Hilton; Warren S Alexander
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Thrombopoietin (TPO) acting via its receptor Mpl is the major cytokine regulator of platelet number. To precisely define the role of specific hematopoietic cells in TPO dependent hematopoiesis, we generated mice that express the Mpl receptor normally on stem/progenitor cells but lack expression on megakaryocytes and platelets ( MplPF4cre/PF4cre . MplPF4cre/PF4cre mice displayed profound megakaryocytosis and thrombocytosis with a remarkable expansion of megakaryocyte-committed and multipotential...
Topic: Cell Biology
Source: http://biorxiv.org/content/early/2014/03/19/003459
biorxiv
by Dent Earl; Ngan K Nguyen; Glenn Hickey; Robert S. Harris; Stephen Fitzgerald; Kathryn Beal; Igor Seledtsov; Vladimir Molodtsov; Brian Raney; Hiram Clawson; Jaebum Kim; Carsten Kemena; Jia-Ming Chang; Ionas Erb; Alexander Poliakov; Minmei Hou; Javier Herrero; Victor Solovyev; Aaron E. Darling; Jian Ma; Cedric Notredame; Michael Brudno; Inna Dubchak; David Haussler; Benedict Paten
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Background: Multiple sequence alignments (MSAs) are a prerequisite for a wide variety of evolutionary analyses. Published assessments and benchmark datasets for protein and, to a lesser extent, global nucleotide MSAs are available, but less effort has been made to establish benchmarks in the more general problem of whole genome alignment (WGA). Results: Using the same model as the successful Assemblathon competitions, we organized a competitive evaluation in which teams submitted their...
Topic: Bioinformatics
Source: http://biorxiv.org/content/early/2014/03/10/003285
biorxiv
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How does the regulatory machinery of an animal cell ensure its survival during large-scale biochemical and phenotypic transitions? When a cell is strongly perturbed by an environmental stimulus, it can either die or persist with compensatory changes. But what do the dynamics of individual genes look like during this process of adaptation? In a previous technical paper, two approaches (drug treatments and polysome isolation) were used in tandem to demonstrate the effects of perturbation on...
Topic: Systems Biology
Source: http://biorxiv.org/content/early/2014/07/02/006775
biorxiv
by Thomas Anantharaman; Bud (Bhubaneswar) Mishra
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The genomic data that can be collected from a single DNA molecule by the best chemical and optical methods (e.g., using technologies from OpGen, BioNanoGenomics, NABSys, PacBio, etc.) are badly corrupted by many poorly understood noise processes. Thus, single molecule technology derives its utility through powerful probabilistic modeling, which can provide precise lower and upper bounds on various experimental parameters to create the correct map or validate sequence assembly. As an example,...
Topic: Genomics
Source: http://biorxiv.org/content/early/2013/11/22/000844
biorxiv
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Annotations of gene structures and regulatory elements can inform genome-wide association studies (GWAS). However, choosing the relevant annotations for interpreting an association study of a given trait remains challenging. We describe a statistical model that uses association statistics computed across the genome to identify classes of genomic element that are enriched or depleted for loci that influence a trait. The model naturally incorporates multiple types of annotations. We applied the...
Topic: Genomics
Source: http://biorxiv.org/content/early/2014/02/25/000752
biorxiv
by Alexander Franks; Florian Markowetz; Edoardo Airoldi
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Building better models of cellular pathways is one of the major challenges of systems biology and functional genomics. There is a need for methods to build on established expert knowledge and reconcile it with results of high-throughput studies. Moreover, the available data sources are heterogeneous and need to be combined in a way specific for the part of the pathway in which they are most informative. Here, we present a compartment specific strategy to integrate edge, node and path data for...
Topic: Genomics
Source: http://biorxiv.org/content/early/2014/06/23/006478
biorxiv
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Correlations in neuronal spike times are thought to be key to processing in many neural systems. Many measures have been proposed to summarise these correlations and of these the correlation index is widely used and is the standard in studies of spontaneous retinal activity. We show that this measure has two undesirable properties: it is unbounded above and confounded by firing rate. We list properties needed for a measure to fairly quantify and compare correlations and we propose a novel...
Topic: Neuroscience
Source: http://biorxiv.org/content/early/2014/09/09/006635
biorxiv
by Mark D Robinson; Abdullah Kahraman; Charity W Law; Helen Lindsay; Malgorzata Nowicka; Lukas M Weber; Xiaobei Zhou
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DNA methylation, and specifically the reversible addition of methyl groups at CpG dinucleotides genome-wide, represents an important layer that is associated with the regulation of gene expression. In particular, aberrations in the methylation status have been noted across a diverse set of pathological states, including cancer. With the rapid development and uptake of large scale sequencing of short DNA fragments, there has been an explosion of data analytic methods for processing and...
Topic: Bioinformatics
Source: http://biorxiv.org/content/early/2014/08/29/007120
biorxiv
by Lucía Durrieu; Rikard Johansson; Alan Bush; David L.I. Janzén; Martin Gollvik; Gunnar Cedersund; Alejandro Colman-Lerner
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Regulation of nuclear transport is a key cellular function involved in many central processes, such as gene expression regulation and signal transduction. Rates of protein movement between cellular compartments can be measured by FRAP. However, no standard and reliable methods to calculate transport rates exist. Here we introduce a method to extract import and export rates, suitable for noisy single cell data. This method consists of microscope procedures, routines for data processing, an ODE...
Topic: Biophysics
Source: http://biorxiv.org/content/early/2014/01/11/001768
biorxiv
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Eukaryotes produce large numbers of small non-coding RNAs that act as specificity determinants for various gene-regulatory complexes. These include microRNAs (miRNAs), endogenous short interfering RNAs (siRNAs), and Piwi-associated RNAs (piRNAs). These RNAs can be discovered, annotated, and quantified using small RNA-seq, a variant RNA-seq method based on highly parallel sequencing. Alignment to a reference genome is a critical step in analysis of small RNA-seq data. Because of their small size...
Topic: Bioinformatics
Source: http://biorxiv.org/content/early/2014/07/23/007427
biorxiv
by Kathleen M Fisch; Tobias Meißner; Louis Gioia; Jean-Christophe Ducom; Tristan Carland; Salvatore Loguercio; Andrew I. Su
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Omics Pipe (https://bitbucket.org/sulab/omics_pipe) is a computational platform that automates multi-omics data analysis pipelines on high performance compute clusters and in the cloud. It supports best practice published pipelines for RNA-seq, miRNA-seq, Exome-seq, Whole Genome sequencing, ChIP-seq analyses and automatic processing of data from The Cancer Genome Atlas. Omics Pipe provides researchers with a tool for reproducible, open source and extensible next generation sequencing analysis.
Topic: Bioinformatics
Source: http://biorxiv.org/content/early/2014/08/23/008383
biorxiv
by Elizabeth A Williams; Markus Conzelmann; Gáspár Jékely
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During larval settlement and metamorphosis, marine invertebrates undergo changes in habitat, morphology, behavior and physiology. This change between life-cycle stages is often associated with a change in diet or a transition between a non-feeding and a feeding form. How larvae regulate changes in feeding during this life cycle transition is not well understood. Neuropeptides are known to regulate several aspects of feeding, such as food search, ingestion and digestion. The marine annelid...
Topic: Zoology
Source: http://biorxiv.org/content/early/2014/09/06/008854
biorxiv
by Haoyang Cai; Nitin Kumar; Homayoun C Bagheri; Christian von Mering; Mark Robinson; Michael Baudis
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Background Chromothripsis is a recently discovered phenomenon of genomic rearrangement, possibly arising during a single genome-shattering event. This could provide an alternative paradigm in cancer development, replacing the gradual accumulation of genomic changes with a one-off catastrophic event. However, the term has been used with varying operational definitions, with the minimal consensus being a large number of locally clustered copy number aberrations. The mechanisms underlying these...
Topic: Genomics
Source: http://biorxiv.org/content/early/2014/01/13/001776.1
biorxiv
by Aline Lefebvre; Anita Beggiato; Thomas Bourgeron; Roberto Toro
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The corpus callosum -- the main pathway for long-distance inter-hemispheric integration in the human brain -- has been frequently reported to be smaller among autistic patients compared with non-autistic controls. We conducted a meta-analysis of the literature which suggested a statistically significant difference. However, the studies included were heavily underpowered: on average only 20% power to detect differences of 0.3 standard deviations, which makes it difficult to establish the reality...
Topic: Neuroscience
Source: http://biorxiv.org/content/early/2014/02/15/002691
biorxiv
by Henrike Heyne; Susann Lautenschlaeger; Ronald Nelson; François Besnier; Maxime Rotival; Alexander Cagan; Rimma Kozhemyakina; Irina Plyusnina; Lyudmila Trut; Orjan Carlborg; Enrico Petretto; Leonid Kruglyak; Svante Pääbo; Torsten Schoeneberg; Frank Albert
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Inter-individual differences in many behaviors are partly due to genetic differences, but the identification of the genes and variants that influence behavior remains challenging. Here, we studied an F2 intercross of two outbred lines of rats selected for tame and aggressive behavior towards humans for more than 64 generations. By using a mapping approach that is able to identify genetic loci segregating within the lines, we identified four times more loci influencing tameness and aggression...
Topic: Genomics
Source: http://biorxiv.org/content/early/2014/04/17/004234
biorxiv
by Eamonn Mallon; Akram Alghamdi; Robert Holdbrook; Ezio Rosato
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Psychoneuroimmunology studies the increasing number of connections between neurobiology, immunology and behaviour. We establish Drosophila melanogaster as a tractable model in this field by demonstrating the effects of the immune response on two fundamental behaviours: sleep and memory ability. We used the Geneswitch system to upregulate peptidoglycan receptor protein (PGRP) expression, thereby stimulating the immune system in the absence of infection. Geneswitch was activated by feeding the...
Topic: Zoology
Source: http://biorxiv.org/content/early/2014/03/12/002717
biorxiv
by Oana Carja; Robert E Furrow; Marc W Feldman
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Stochastic switching is an example of phenotypic bet-hedging, where an individual can switch between different phenotypic states in a fluctuating environment. Although the evolution of stochastic switching has been studied when the environment varies temporally, there has been little theoretical work on the evolution of phenotypic switching under both spatially and temporally fluctuating selection pressures. Here we use a population genetic model to explore the interaction of temporal and...
Topic: Evolutionary Biology
Source: http://biorxiv.org/content/early/2014/03/19/003442-0
biorxiv
by Sebastian Gil Anthony Konietzny; Phillip Byron Pope; Aaron Weimann; Alice Carolyn McHardy
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Background: Efficient industrial processes for converting plant lignocellulosic materials into biofuels are a key challenge in global efforts to use alternative energy sources to fossil fuels. Novel cellulolytic enzymes have been discovered from microbial genomes and metagenomes of microbial communities. However, the identification of relevant genes without known homologs, and elucidation of the lignocellulolytic pathways and protein complexes for different microorganisms remain a challenge....
Topic: Bioinformatics
Source: http://biorxiv.org/content/early/2014/05/21/005355
biorxiv
by Bret S Lesavoy; Suzanne E McGaugh; Mohamed A.F. Noor
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The scuttle fly Megaselia scalaris is a pest species whose larvae consume living or dead plant or animal tissue, and parasitize humans. Although known to exist on most continents, often transported passively with humans, the connectivity between populations has not been investigated. We use mitochondrial cytochrome B sequences to investigate structure among North American isolates of this species. Despite small sample sizes, we detected statistically significant structure among populations....
Topic: Zoology
Source: http://biorxiv.org/content/early/2014/06/13/006288
biorxiv
by Mathieu Larocque; Thierry Chénard; Rafael Najmanovich
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Clostridium difficile is the leading cause of hospital-borne infections occurring when the natural intestinal flora is depleted following antibiotic treatment. We present i MLTC804cdf, an extensively curated reconstructed metabolic network for the C. difficile pathogenic strain 630. i MLTC804cdf contains 804 genes, 705 metabolites and 766 metabolic, 145 exchange and 118 transport reactions. i MLTC804cdf is the most complete and accurate metabolic reconstruction of a gram-positive anaerobic...
Topic: Systems Biology
Source: http://biorxiv.org/content/early/2014/07/25/006932
biorxiv
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The development of CRISPR/Cas9 technologies promises a quantum leap in genome-engineering of model organisms. However, CRISPR-mediated gene targeting reports in Drosophila are still restricted to a few genes, use variable experimental conditions and vary in efficiency, questioning the universal applicability of the method. Here, we developed an efficient, two-step strategy to flexibly engineer the fly genome by combining CRISPR with recombinase-mediated cassette exchange (RMCE). In the first...
Topic: Developmental Biology
Source: http://biorxiv.org/content/early/2014/08/11/007864
biorxiv
by Xia Shen; Jennifer De Jonge; Simon Forsberg; Mats Pettersson; Zheya Sheng; Lars Hennig; Örjan Carlborg
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As Arabidopsis thaliana has colonized a wide range of habitats across the world it is an attractive model for studying the genetic mechanisms underlying environmental adaptation. Here, we used public data from two collections of A. thaliana accessions to associate genetic variability at individual loci with differences in climates at the sampling sites. We use a novel method to screen the genome for plastic alleles that tolerate a broader climate range than the major allele. This approach...
Topic: Genomics
Source: http://biorxiv.org/content/early/2014/04/10/004119
biorxiv
by Yaniv Brandvain; Graham Coop
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Genomic conflicts arise when an allele gains an evolutionary advantage at a cost to organismal fitness. Oo ̈genesis is inherently susceptible to such conflicts because alleles compete to be the product of female meiosis transmitted to the egg. Alleles that distort meiosis in their favor (i.e. meiotic drivers) often decrease organismal fitness, and therefore indirectly favor the evolution of mechanisms to suppress meiotic drive. In this light, many facets of oogenesis and gametogenesis have...
Topic: Evolutionary Biology
Source: http://biorxiv.org/content/early/2014/07/28/005363
biorxiv
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In order to compare stand structure and woody species diversity of subtropical evergreen broadleaf forests along a latitudinal thermal gradient of the Ryukyu Archipelago, tree censuses in a 750 m2 plot in Okinawa Island and a 400 m2 plot in Ishigaki Island were performed. The number of layers increased along a latitudinal thermal gradient from four in the forest of Okinawa Island to five in the forest of Ishigaki Island. The values of Shannon's index and Pielou's index tended to increase from...
Topic: Ecology
Source: http://biorxiv.org/content/early/2014/08/07/007625
biorxiv
by Helena Jambor; Vineeth Surendranath; Alex T. Kalinka; Pavel Mejstrik; Stephan Saalfeld; Pavel Tomancak
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The asymmetric distribution of cytoplasmic components by mRNA localization is critical for eukaryotic cells and affects large numbers of transcripts. How such global subcellular localization of mRNAs is regulated is still unknown. We combined transcriptomics and systematic imaging to determine tissue-specific expression and subcellular localizations of 5862 mRNAs during Drosophila oogenesis. While the transcriptome is stable and alternative splicing and polyadenylation is rare, cytoplasmic...
Topic: Developmental Biology
Source: http://biorxiv.org/content/early/2014/09/09/008938
biorxiv
by Jeanette Baran-Gale; Michael R Erdos; Christina Sison; Alice Young; Emily E Fannin; Peter S Chines; Praveen Sethupathy
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Recent advances in sequencing technology have helped unveil the unexpected complexity and diversity of small RNAs. A critical step in small RNA library preparation for sequencing is the ligation of adapter sequences to both the 5’ and 3’ ends of small RNAs. Two widely used protocols for small RNA library preparation, Illumina v1.5 and Illumina TruSeq, use different pairs of adapter sequences. In this study, we compare the results of small RNA-sequencing between v1.5 and TruSeq and observe a...
Topic: Genomics
Source: http://biorxiv.org/content/early/2013/12/19/001479
biorxiv
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Restriction-site associated genomic markers are a powerful tool for investigating evolutionary questions at the population level, but are limited in their utility at deeper phylogenetic scales where fewer orthologous loci are typically recovered across disparate taxa. While this limitation stems in part from mutations to restriction recognition sites that disrupt data generation, an alternative source of data loss comes from the failure to identify homology during bioinformatic analyses....
Topic: Bioinformatics
Source: http://biorxiv.org/content/early/2013/12/03/001081
biorxiv
by Alejandro Reyes; Carolin Blume; Vicent Pelechano; Petra Jakob; Lars M Steinmetz; Thorsten Zenz; Wolfgang Huber
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Background: Genome sequencing studies of chronic lympoid leukemia (CLL) have provided a comprehensive overview of recurrent somatic mutations in coding genes. One of the most intriguing discoveries has been the prevalence of mutations in the HEAT-repeat domain of the splicing factor SF3B1. A frequently observed variant is predicted to cause the substitution of a lysine with a glutamic acid at position 700 of the protein (K700E). However, the molecular consequences of the mutations are largely...
Topic: Cancer Biology
Source: http://biorxiv.org/content/early/2014/07/13/000992
biorxiv
by Xuewei Chen; Shimin Zuo; Benjamin Schwessinger; Mawsheng Chern; Patrick Canlas; Deling Ruan; Arsalan Daudi; Xiaogang Zhang; Jing Wang; Christopher Petzold; Joshua Heazlewood; Pamela C Ronald
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The rice XA21 immune receptor kinase and the structurally related XA3 receptor, confer immunity to Xanthomonas oryzae pv. oryzae (Xoo), the causal agent of bacterial leaf blight. Here we report the isolation of OsSERK2 (rice somatic embryogenesis receptor kinase 2) and demonstrate that OsSERK2 positively regulates immunity mediated by XA21 and XA3 as well as the rice immune receptor FLS2 (OsFLS2). Rice plants silenced for OsSerk2 display altered morphology and reduced sensitivity to the hormone...
Topic: Plant Biology
Source: http://biorxiv.org/content/early/2013/12/25/000950
biorxiv
by Dina Zielinski; Barak Markus; Mona Sheikh; Melissa Gymrek; Clement Chu; Marta Zaks; Balaji Srinivasan; Jodi D. Hoffman; Dror Aizenbud; Yaniv Erlich
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Hemifacial microsomia (HFM) is the second most common facial anomaly after cleft lip and palate. The phenotype is highly variable and most cases are sporadic. Here, we investigated the disorder in a large pedigree with five affected individuals spanning eight meioses. We performed whole-exome sequencing and a genome-wide survey of segmental variations. Analysis of the exome sequencing results indicated the absence of a pathogenic coding point mutation. Inspection of segmental variations...
Topic: Genetics
Source: http://biorxiv.org/content/early/2013/12/03/001099
biorxiv
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The living state is cognitive at every scale and level of organization. Since it is possible to associate a broad class of cognitive processes with 'dual' information sources, many pathologies can be addressed using statistical models based on the Shannon Coding, the Shannon-McMillan Source Coding, the Rate Distortion, and the Data Rate Theorems, as these impose powerful necessary condition constraints on information generation and exchange, and on system control. Deterministic-but-for-error...
Topic: Systems Biology
Source: http://biorxiv.org/content/early/2014/04/23/003384
biorxiv
by Laura Vann; Thomas Kono; Tanja Pyha ̈j ̈arvi; Matthew B Hufford; Jeffrey Ross-Ibarra
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Premise of the study: The teosinte branched1 (tb1) gene is a major QTL controlling branching differences between maize and its wild progenitor, teosinte. The insertion of a transposable element (Hopscotch) upstream of tb1 is known to enhance the gene's expression, causing reduced tillering in maize. Observations of the maize tb1 allele in teosinte and estimates of an insertion age of the Hopscotch that predates domestication led us to investigate its prevalence and potential role in teosinte....
Topic: Evolutionary Biology
Source: http://biorxiv.org/content/early/2014/09/11/005819
Quantification of RNA transcripts with RNA-Seq is inaccurate due to positional fragmentation bias, which is not represented appropriately by current statistical models of RNA-Seq data. Another, less investigated, source of error is the inaccuracy of transcript start and end annotations. This article introduces the Mix2 (rd. mixquare) model, which uses a mixture of probability distributions to model the transcript specific positional fragment bias. The parameters of the Mix2 model can be...
Topic: Bioinformatics
Source: http://biorxiv.org/content/early/2014/06/04/005918
biorxiv
by Àlex Bravo; Janet Piñero; Núria Queralt; Michael Rautschka; Laura I. Furlong
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Background Current biomedical research needs to leverage and exploit the large amount of information reported in publications. Automated text mining approaches, in particular those aimed at finding relationships between entities, are key for identification of actionable knowledge from free text repositories. We present the BeFree system aimed at identifying relationships between biomedical entities with a special focus on genes and their associated diseases. Results By exploiting...
Topic: Bioinformatics
Source: http://biorxiv.org/content/early/2014/07/24/007443
biorxiv
by Brendan Bulik-Sullivan; Po-Ru Loh; Hilary Finucane; Stephan Ripke; Jian Yang; Schizophrenia Working Group Psychiatric Genomics Consortium; Nick Patterson; Mark J Daly; Alkes L Price; Benjamin M Neale
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Both polygenicity (i.e. many small genetic effects) and confounding biases, such as cryptic relatedness and population stratification, can yield inflated distributions of test statistics in genome-wide association studies (GWAS). However, current methods cannot distinguish between inflation from bias and true signal from polygenicity. We have developed an approach that quantifies the contributions of each by examining the relationship between test statistics and linkage disequilibrium (LD). We...
Topic: Genomics
Source: http://biorxiv.org/content/early/2014/02/21/002931
biorxiv
by Thomas F. Willems; Melissa Gymrek; Gareth Highnam; - The 1000 Genomes Project; David Mittelman; Yaniv Erlich
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Short Tandem Repeats are among the most polymorphic loci in the human genome. These loci play a role in the etiology of a range of genetic diseases and have been frequently utilized in forensics, population genetics, and genetic genealogy. Despite this plethora of applications, little is known about the variation of most STRs in the human population. Here, we report the largest-scale analysis of human STR variation to date. We collected information for nearly 700,000 STR loci across over 1,000...
Topic: Genomics
Source: http://biorxiv.org/content/early/2014/07/10/004671
biorxiv
by Endre Sebestyén; Michał Zawisza; Eduardo Eyras
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Cancer genomics has been instrumental to determine the genetic alterations that are predictive of various tumor conditions. However, the majority of these alterations occur at low frequencies, motivating the need to expand the catalogue of cancer signatures. Alternative pre-mRNA splicing alterations, which bear major importance for the understanding of cancer, have not been exhaustively studied yet in the context of recent cancer genome projects. In this article we analyze RNA sequencing data...
Topic: Bioinformatics
Source: http://biorxiv.org/content/early/2014/07/07/006908
biorxiv
by Jared O'Connell; Ole Schulz-Trieglaff; Emma Carlson; Matthew M Hims; Niall A Gormley; Anthony J Cox
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Motivation: Mate pair protocols add to the utility of paired-end sequencing by boosting the genomic distance spanned by each pair of reads, potentially allowing larger repeats to be bridged and resolved. The Illumina Nextera Mate Pair (NMP) protocol employs a circularisation-based strategy that leaves behind 38bp adapter sequences which must be computationally removed from the data. While "adapter trimming" is a well-studied area of bioinformatics, existing tools do not fully exploit...
Topic: Bioinformatics
Source: http://biorxiv.org/content/early/2014/08/06/007666
biorxiv
by Mick Watson; Marian Thomson; Judith Risse; Javier Santoyo-Lopez; Richard Talbot; Karim Gharbi; Mark Blaxter
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Motivation: The Oxford Nanopore MinION device represents a unique sequencing technology. As a mobile sequencing device powered by the USB port of a laptop, the MinION has huge potential applications. To enable these applications, the bioinformatics community will need to design and build a suite of tools specifically for MinION data. Results: Here we present poRe, a package for the statistical software R that enables users to manipulate, organize, summarise and visualize MinION nanopore...
Topic: Bioinformatics
Source: http://biorxiv.org/content/early/2014/07/29/007567
biorxiv
by Thomas Turner; Christopher C Giauque; Daniel R Schrider; Andrew D Kern
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Thirty four years ago, it was postulated that natural populations of Drosophila melanogaster are comprised of two behavioral morphs termed "rover" and "sitter", and that this variation is caused mainly by large-effect alleles at a single locus. Since that time, considerable data has been amassed that compares the behavior and physiology of these morphs. Contrary to common assertions, however, published support for the existence of common large effect alleles in nature is...
Topic: Evolutionary Biology
Source: http://biorxiv.org/content/early/2014/04/20/004325
biorxiv
by Luwen Ning; Guan Wang; Zhoufang Li; Wen Hu; Qingming Hou; Yin Tong; Meng Zhang; Li Qin; Xiaoping Chen; Heng-Ye Man; Pinghua Liu; Jiankui He
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Single-cell genomic analysis has grown rapidly in recent years and will find widespread applications in various fields of biology, including cancer biology, development, immunology, pre-implantation genetic diagnosis, and neurobiology. In this study, we amplified genomic DNA from individual hippocampal neurons using one of three single-cell DNA amplification methods (multiple annealing and looping-based amplification cycles (MALBAC), multiple displacement amplification (MDA), and GenomePlex...
Topic: Genomics
Source: http://biorxiv.org/content/early/2014/04/21/004366
biorxiv
by Nuno A Fonseca; John A Marioni; Alvis Brazma
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Accurately quantifying gene expression levels is a key goal of experiments using RNA-sequencing to assay the transcriptome. This typically requires aligning the short reads generated to the genome or transcriptome before quantifying expression of pre-defined sets of genes. Differences in the alignment/quantification tools can have a major effect upon the expression levels found with important consequences for biological interpretation. Here we address two main issues: do different analysis...
Topic: Bioinformatics
Source: http://biorxiv.org/content/early/2014/07/15/005207
biorxiv
by Jingqun Ao; Yinnan Mu; Li-Xin Xiang; DingDing Fan; MingJi Feng; Shicui Zhang; Qiong Shi; Lv-Yun Zhu; Ting Li; Yang Ding; Li Nie; Qiuhua Li; Wei-ren Dong; Liang Jiang; Bing Sun; XinHui Zhang; Mingyu Li; Hai-Qi Zhang; ShangBo Xie; YaBing Zhu; XuanTing Jiang; Xianhui Wang; Pengfei Mu; Wei Chen; Zhen Yue; Zhuo Wang; Jun Wang; Jian-Zhong Shao; Xinhua Chen
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The large yellow croaker Larimichthys crocea (L. crocea) is one of the most economically important marine fish in China and East Asian countries. It also exhibits peculiar behavioral and physiological characteristics, especially sensitive to various environmental stresses, such as hypoxia and air exposure. These traits may render L. crocea a good model for investigating the response mechanisms to environmental stress. To understand the molecular and genetic mechanisms underlying the adaptation...
Topic: Genomics
Source: http://biorxiv.org/content/early/2014/08/18/008136
biorxiv
by Itay Maza; Inbal Casoi; Sergey Viukov; Yoach Rais; Asaf Zviran; Shay Geula; Vladislav Krupalnik; Mirie Zerbib; Rada Massarwa; Noa Novershtern; Jacob Hanna
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Recent reports have proposed a new paradigm for obtaining mature somatic cell types from fibroblasts without going through a pluripotent state, by briefly expressing canonical iPSC reprogramming factors Oct4, Sox2, Klf4, c-Myc (abbreviated as OSKM) in cells expanded in lineage differentiation promoting conditions. Here we apply genetic lineage tracing for endogenous Nanog locus and X chromosome reactivation during OSKM induced trans-differentiation, as these molecular events mark final stages...
Topic: Developmental Biology
Source: http://biorxiv.org/content/early/2014/08/23/008284
biorxiv
by Alexander Dilthey; Charles J Cox; Zamin Iqbal; Matthew R Nelson; Gil McVean
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In humans and many other species, while much is known about the extent and structure of genetic variation, such information is typically not used in assembling novel genomes. Rather, a single reference is used against which to map reads, which can lead to poor characterisation of regions of high sequence or structural diversity. Here, we introduce a population reference graph, which combines multiple reference sequences as well as catalogues of SNPs and short indels. The genomes of novel...
Topic: Genomics
Source: http://biorxiv.org/content/early/2014/07/08/006973
biorxiv
by Fabricio Baccaro; João Araújo; Harry Evans; Jorge Souza; Bill Magnusson; David Hughes
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Parasites and hosts are intimately associated such that changes in the diversity of one partner are thought to lead to changes in the other. We investigated this linked diversity hypothesis in a specialized ant-Ophiocordyceps system in three forests across 750 km in Central Amazonia. All species belonging to the fungal genus Ophiocordyceps associated with ants have evolved some degree of behavioral control to increase their own transmission, but the leaf-biting behavior is the most complex form...
Topic: Ecology
Source: http://biorxiv.org/content/early/2014/01/19/001925
biorxiv
by Lauren E Quevillon; Ephraim M Hanks; Shweta Bansal; David P Hughes
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abstract forthcoming.
Topic: Ecology
Source: http://biorxiv.org/content/early/2014/02/11/002519
biorxiv
by Annalise Paaby; Amelia White; David Riccardi; Kristin Gunsalus; Fabio Piano; Matthew Rockman
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Conditionally functional mutations are an important class of natural genetic variation, yet little is known about their prevalence in natural populations or their contribution to disease risk. Here, we describe a vast reserve of cryptic genetic variation, alleles that are normally silent but which affect phenotype when the function of other genes is perturbed, in the gene networks of C. elegans embryogenesis. We find evidence that cryptic-effect loci are ubiquitous and segregate at intermediate...
Topic: Evolutionary Biology
Source: http://biorxiv.org/content/early/2014/08/28/008532
biorxiv
by Nicola Nadeau; Mayte Ruiz; Patricio Salazar; Brian Counterman; Jose Alejandro Medina; Humberto Ortiz-Zuazaga; Anna Morrison; W. Owen McMillan; Chri Jiggins; Riccardo Papa
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Hybrid zones can be valuable tools for studying evolution and identifying genomic regions responsible for adaptive divergence and underlying phenotypic variation. Hybrid zones between subspecies of Heliconius butterflies can be very narrow and are maintained by strong selection acting on colour pattern. The co-mimetic species H. erato and H. melpomene have parallel hybrid zones where both species undergo a change from one colour pattern form to another. We use restriction associated DNA...
Topic: Evolutionary Biology
Source: http://biorxiv.org/content/early/2013/11/11/000208
biorxiv
by Remco Stam; Graham Motion; Petra C. Boevink; Edgar Huitema
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Phytophthora spp. secrete vast arrays of effector molecules upon infection. A main class of intracellular effectors are the CRNs. They are translocated into the host cell and specifically localise to the nucleus where they are thought to perturb many different cellular processes. Although CRN proteins have been implicated as effectors, direct evidence of CRN mediated perturbation of host processes has been lacking. Here we show that a conserved CRN effector from P. capsici directly binds to...
Topic: Plant Biology
Source: http://biorxiv.org/content/early/2013/12/11/001248
biorxiv
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Henrich (2004) argued that larger populations can better maintain complex technologies because they contain more highly skilled people whom others can imitate. His original model, however, did not distinguish the effects of population size from population density or network size; a learner's social network included the entire population. Does population size remain important when populations are subdivided and networks are realistically small? I use a mathematical model to show that population...
Topic: Evolutionary Biology
Source: http://biorxiv.org/content/early/2013/12/31/001529
biorxiv
by Sterling Sawaya; James Boocock; Mik Black; Neil Gemmell
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Pausing of DNA polymerase can indicate the presence of a DNA structure that differs from the canonical double-helix. Here we detail a method to investigate how polymerase pausing in the Pacific Biosciences sequencer reads can be related to DNA structure. The Pacific Biosciences sequencer uses optics to view a polymerase and its interaction with a single DNA molecule in real-time, offering a unique way to detect potential alternative DNA structures. We have developed a new way to examine...
Topic: Bioinformatics
Source: http://biorxiv.org/content/early/2013/12/02/001024
biorxiv
by Janine O Ilagan; Aravind Ramakrishnan; Brian Hayes; Michele E Murphy; Ahmad S Zebari; Philip Bradley; Robert K Bradley
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Whole-exome sequencing studies have identified common mutations affecting genes encoding components of the RNA splicing machinery in hematological malignancies. Here, we sought to determine how mutations affecting the 3' splice site recognition factor U2AF1 alter its normal role in RNA splicing. We find that U2AF1 mutations influence the similarity of splicing programs in leukemias, but do not give rise to widespread splicing failure. U2AF1 mutations cause differential splicing of hundreds of...
Topic: Genomics
Source: http://biorxiv.org/content/early/2014/06/28/001107
biorxiv
by Simon H. Martin; John W. Davey; Chris D. Jiggins
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Several methods have been proposed to test for introgression across genomes. One method tests for a genome-wide excess of shared derived alleles between taxa using Patterson?s D statistic, but does not establish which loci show such an excess or whether the excess is due to introgression or ancestral population structure. Several recent studies have extended the use of D by applying the statistic to small genomic regions, rather than genome-wide. Here, we use simulations and whole genome data...
Topic: Evolutionary Biology
Source: http://biorxiv.org/content/early/2014/08/20/001347
biorxiv
by Guopeng Ren; Stephen S. Young; Lin Wang; Wei Wang; Yongcheng Long; Ruidong Wu; Junsheng Li; Jianguo Zhu; Douglas W. Yu
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There is profound interest in knowing the degree to which Chinas institutions are capable of protecting its natural forests and biodiversity in the face of economic and political change. Chinas two most important forest protection policies are its National Forest Protection Program (NFPP) and its National-level Nature Reserves (NNRs). The NFPP was implemented in 17 provinces starting in the year 2000 in response to deforestation-caused flooding. We used MODIS data (MOD13Q1) to estimate forest...
Topic: Ecology
Source: http://biorxiv.org/content/early/2013/11/25/000893
biorxiv
by Yongsheng Li; Yunpeng Zhang; Shengli Li; Jianping Lu; Juan Chen; Zheng Zhao; Jing Bai; Juan Xu; Xia Li
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The development of human breast cancer is driven by changes in the genetic and epigenetic landscape of the cell. Despite growing appreciation of the importance of epigenetics in breast cancers, our knowledge of epigenetic alterations of non-coding RNAs (ncRNAs) in breast cancers remains limited. Here, we explored the epigenetic patterns of ncRNAs in breast cancers via a sequencing-based comparative methylome analysis, mainly focusing on two most popular ncRNA biotypes, long non-coding RNAs...
Topic: Bioinformatics
Source: http://biorxiv.org/content/early/2014/01/28/002204
biorxiv
by Emilia S. Gracia; Charissa de Bekker; Jim Russell; Kezia Manlove; Ephraim Hanks; David P. Hughes
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Every level of biological organization from cells to societies require that composing units come together to form parts of a bigger unit (1). Our knowledge of how behavioral manipulating parasites change social interactions between social hosts is limited. Here we use an endoparasite to observe changes in social interactions between infected and healthy ants, using trophallaxis (liquid food exchange) and spatial data as proxies for food sharing and social segregation. We found no change in...
Topic: Ecology
Source: http://biorxiv.org/content/early/2014/02/12/002501
biorxiv
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Background One of the most common goals of hierarchical clustering is finding those branches of a tree that form quantifiably distinct data subtypes. Achieving this goal in a statistically meaningful way requires (a) a measure of distinctness of a branch and (b) a test to determine the significance of the observed measure, applicable to all branches and across multiple scales of dissimilarity. Results We formulate a method termed Tree Branches Evaluated Statistically for Tightness (TBEST) for...
Topic: Bioinformatics
Source: http://biorxiv.org/content/early/2014/06/05/002188