Showing papers by "Richard Durbin published in 2013"
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University of California, Davis1, Yale University2, Laval University3, Joint Genome Institute4, Centre national de la recherche scientifique5, École normale supérieure de Cachan6, Wayne State University7, University of Georgia8, University of Udine9, Wellcome Trust Sanger Institute10, University of California, Santa Cruz11, University of Notre Dame12, European Bioinformatics Institute13, Duke University14, Baylor College of Medicine15, Broad Institute16, University of Washington17, University of Maryland, College Park18, University of California, Berkeley19, University of Lisbon20, University of California, San Francisco21, Howard Hughes Medical Institute22, Cold Spring Harbor Laboratory23, Royal Institute of Technology24
TL;DR: The Assemblathon 2 as mentioned in this paper presented a variety of sequence data to be assembled for three vertebrate species (a bird, a fish, and a snake) from 21 participating teams.
Abstract: Background - The process of generating raw genome sequence data continues to become cheaper, faster, and more accurate. However, assembly of such data into high-quality, finished genome sequences remains challenging. Many genome assembly tools are available, but they differ greatly in terms of their performance (speed, scalability, hardware requirements, acceptance of newer read technologies) and in their final output (composition of assembled sequence). More importantly, it remains largely unclear how to best assess the quality of assembled genome sequences. The Assemblathon competitions are intended to assess current state-of-the-art methods in genome assembly. Results - In Assemblathon 2, we provided a variety of sequence data to be assembled for three vertebrate species (a bird, a fish, and snake). This resulted in a total of 43 submitted assemblies from 21 participating teams. We evaluated these assemblies using a combination of optical map data, Fosmid sequences, and several statistical methods. From over 100 different metrics, we chose ten key measures by which to assess the overall quality of the assemblies. Conclusions - Many current genome assemblers produced useful assemblies, containing a significant representation of their genes, regulatory sequences, and overall genome structure. However, the high degree of variability between the entries suggests that there is still much room for improvement in the field of genome assembly and that approaches which work well in assembling the genome of one species may not necessarily work well for another.
690 citations
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Yale University1, BC Cancer Agency2, Laval University3, Joint Genome Institute4, École normale supérieure de Cachan5, Centre national de la recherche scientifique6, Wayne State University7, University of Georgia8, Wellcome Trust Sanger Institute9, University of California, Santa Cruz10, University of Notre Dame11, European Bioinformatics Institute12, Duke University13, Baylor College of Medicine14, Broad Institute15, University of Washington16, University of Maryland, College Park17, University of Hong Kong18, French Institute for Research in Computer Science and Automation19, California Institute for Quantitative Biosciences20, University of Lisbon21, University of California, Berkeley22, Howard Hughes Medical Institute23, University of California, San Francisco24, Cold Spring Harbor Laboratory25, Royal Institute of Technology26, University of Udine27
TL;DR: The Assemblathon 2 as discussed by the authors presented a variety of sequence data to be assembled for three vertebrate species (a bird, a fish, and a snake) from 21 participating teams.
Abstract: Background: The process of generating raw genome sequence data continues to become cheaper, faster, and more accurate. However, assembly of such data into high-quality, finished genome sequences remains challenging. Many genome assembly tools are available, but they differ greatly in terms of their performance (speed, scalability, hardware requirements, acceptance of newer read technologies) and in their final output (composition of assembled sequence). More importantly, it remains largely unclear how to best assess the quality of assembled genome sequences. The Assemblathon competitions are intended to assess current state-of-the-art methods in genome assembly. Results: In Assemblathon 2, we provided a variety of sequence data to be assembled for three vertebrate species (a bird, a fish, and snake). This resulted in a total of 43 submitted assemblies from 21 participating teams. We evaluated these assemblies using a combination of optical map data, Fosmid sequences, and several statistical methods. From over 100 different metrics, we chose ten key measures by which to assess the overall quality of the assemblies. (Continued on next page)
602 citations
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TL;DR: Skin showed the most age-related gene expression changes of all the tissues investigated, with many of the genes being previously implicated in fatty acid metabolism, mitochondrial activity, cancer and splicing.
Abstract: Background: Previous studies have demonstrated that gene expression levels change with age These changes are hypothesized to influence the aging rate of an individual We analyzed gene expression changes with age in abdominal skin, subcutaneous adipose tissue and lymphoblastoid cell lines in 856 female twins in the age range of 39-85 years Additionally, we investigated genotypic variants involved in genotype-by-age interactions to understand how the genomic regulation of gene expression alters with age Results: Using a linear mixed model, differential expression with age was identified in 1,672 genes in skin and 188 genes in adipose tissue Only two genes expressed in lymphoblastoid cell lines showed significant changes with age Genes significantly regulated by age were compared with expression profiles in 10 brain regions from 100 postmortem brains aged 16 to 83 years We identified only one age-related gene common to the three tissues There were 12 genes that showed differential expression with age in both skin and brain tissue and three common to adipose and brain tissues Conclusions: Skin showed the most age-related gene expression changes of all the tissues investigated, with many of the genes being previously implicated in fatty acid metabolism, mitochondrial activity, cancer and splicing A significant proportion of age-related changes in gene expression appear to be tissue-specific with only a few genes sharing an age effect in expression across tissues More research is needed to improve our understanding of the genetic influences on aging and the relationship with age-related diseases
262 citations
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TL;DR: The most parsimonious model for the majority of loci mapped using either approach was the effect of an allele private to one founder, which could validate examples of pleiotropic effects and complex allelic series at a locus.
Abstract: A large fraction of human complex trait heritability is due to a high number of variants with small marginal effects and their interactions with genotype and environment. Such alleles are more easily studied in model organisms, where environment, genetic makeup, and allele frequencies can be controlled. Here, we examine the effect of natural genetic variation on heritable traits in a very large pool of baker’s yeast from a multiparent 12th generation intercross. We selected four representative founder strains to produce the Saccharomyces Genome Resequencing Project (SGRP)-4X mapping population and sequenced 192 segregants to generate an accurate genetic map. Using these individuals, we mapped 25 loci linked to growth traits under heat stress, arsenite, and paraquat, the majority of which were best explained by a diverging phenotype caused by a single allele in one condition. By sequencing pooled DNA from millions of segregants grown under heat stress, we further identified 34 and 39 regions selected in haploid and diploid pools, respectively, with most of the selection against a single allele. While the most parsimonious model for the majority of loci mapped using either approach was the effect of an allele private to one founder, we could validate examples of pleiotropic effects and complex allelic series at a locus. SGRP-4X is a deeply characterized resource that provides a framework for powerful and high-resolution genetic analysis of yeast phenotypes and serves as a test bed for testing avenues to attack human complex traits.
129 citations
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TL;DR: Creators of software widely used in computational biology discuss the factors that contributed to their success and suggest ideas for future generations of software developers.
Abstract: Creators of software widely used in computational biology discuss the factors that contributed to their success
35 citations
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TL;DR: A genome-wide survey of genetic variation in gorillas using a reduced representation sequencing approach, focusing on the two lowland subspecies, suggests that despite their maintaining an overall level of genetic diversity equal to or greater than that of humans, population decline has been a significant factor in recent and long-term pressures on wild gorilla populations.
Abstract: All non-human great apes are endangered in the wild, and it is therefore important to gain an understanding of their demography and genetic diversity. Whole genome assembly projects have provided an invaluable foundation for understanding genetics in all four genera, but to date genetic studies of multiple individuals within great ape species have largely been confined to mitochondrial DNA and a small number of other loci. Here, we present a genome-wide survey of genetic variation in gorillas using a reduced representation sequencing approach, focusing on the two lowland subspecies. We identify 3,006,670 polymorphic sites in 14 individuals: 12 western lowland gorillas (Gorilla gorilla gorilla) and 2 eastern lowland gorillas (Gorilla beringei graueri). We find that the two species are genetically distinct, based on levels of heterozygosity and patterns of allele sharing. Focusing on the western lowland population, we observe evidence for population substructure, and a deficit of rare genetic variants suggesting a recent episode of population contraction. In western lowland gorillas, there is an elevation of variation towards telomeres and centromeres on the chromosomal scale. On a finer scale, we find substantial variation in genetic diversity, including a marked reduction close to the major histocompatibility locus, perhaps indicative of recent strong selection there. These findings suggest that despite their maintaining an overall level of genetic diversity equal to or greater than that of humans, population decline, perhaps associated with disease, has been a significant factor in recent and long-term pressures on wild gorilla populations.
27 citations
01 Jan 2013
5 citations