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Featured researches published by Dent Earl.


Conservation Genetics Resources | 2012

STRUCTURE HARVESTER: a website and program for visualizing STRUCTURE output and implementing the Evanno method

Dent Earl; Bridgett M. vonHoldt

We present STRUCTURE HARVESTER (available at http://taylor0.biology.ucla.edu/structureHarvester/), a web-based program for collating results generated by the program STRUCTURE. The program provides a fast way to assess and visualize likelihood values across multiple values of K and hundreds of iterations for easier detection of the number of genetic groups that best fit the data. In addition, STRUCTURE HARVESTER will reformat data for use in downstream programs, such as CLUMPP.


Nature | 2010

Genome-wide SNP and haplotype analyses reveal a rich history underlying dog domestication

Bridgett M. vonHoldt; John P. Pollinger; Kirk E. Lohmueller; Eunjung Han; Heidi G. Parker; Pascale Quignon; Jeremiah D. Degenhardt; Adam R. Boyko; Dent Earl; Adam Auton; Andrew R. Reynolds; Kasia Bryc; Abra Brisbin; James C. Knowles; Dana S. Mosher; Tyrone C. Spady; Abdel G. Elkahloun; Eli Geffen; Malgorzata Pilot; Włodzimierz Jędrzejewski; Claudia Greco; Ettore Randi; Danika L. Bannasch; Alan N. Wilton; Jeremy Shearman; Marco Musiani; Michelle Cargill; Paul Glyn Jones; Zuwei Qian; Wei Huang

Advances in genome technology have facilitated a new understanding of the historical and genetic processes crucial to rapid phenotypic evolution under domestication. To understand the process of dog diversification better, we conducted an extensive genome-wide survey of more than 48,000 single nucleotide polymorphisms in dogs and their wild progenitor, the grey wolf. Here we show that dog breeds share a higher proportion of multi-locus haplotypes unique to grey wolves from the Middle East, indicating that they are a dominant source of genetic diversity for dogs rather than wolves from east Asia, as suggested by mitochondrial DNA sequence data. Furthermore, we find a surprising correspondence between genetic and phenotypic/functional breed groupings but there are exceptions that suggest phenotypic diversification depended in part on the repeated crossing of individuals with novel phenotypes. Our results show that Middle Eastern wolves were a critical source of genome diversity, although interbreeding with local wolf populations clearly occurred elsewhere in the early history of specific lineages. More recently, the evolution of modern dog breeds seems to have been an iterative process that drew on a limited genetic toolkit to create remarkable phenotypic diversity.


Bioinformatics | 2010

Inference of patient-specific pathway activities from multi-dimensional cancer genomics data using PARADIGM

Charles J. Vaske; Stephen Charles Benz; J. Zachary Sanborn; Dent Earl; Christopher W. Szeto; Jingchun Zhu; David Haussler; Joshua M. Stuart

Motivation: High-throughput data is providing a comprehensive view of the molecular changes in cancer tissues. New technologies allow for the simultaneous genome-wide assay of the state of genome copy number variation, gene expression, DNA methylation and epigenetics of tumor samples and cancer cell lines. Analyses of current data sets find that genetic alterations between patients can differ but often involve common pathways. It is therefore critical to identify relevant pathways involved in cancer progression and detect how they are altered in different patients. Results: We present a novel method for inferring patient-specific genetic activities incorporating curated pathway interactions among genes. A gene is modeled by a factor graph as a set of interconnected variables encoding the expression and known activity of a gene and its products, allowing the incorporation of many types of omic data as evidence. The method predicts the degree to which a pathways activities (e.g. internal gene states, interactions or high-level ‘outputs’) are altered in the patient using probabilistic inference. Compared with a competing pathway activity inference approach called SPIA, our method identifies altered activities in cancer-related pathways with fewer false-positives in both a glioblastoma multiform (GBM) and a breast cancer dataset. PARADIGM identified consistent pathway-level activities for subsets of the GBM patients that are overlooked when genes are considered in isolation. Further, grouping GBM patients based on their significant pathway perturbations divides them into clinically-relevant subgroups having significantly different survival outcomes. These findings suggest that therapeutics might be chosen that target genes at critical points in the commonly perturbed pathway(s) of a group of patients. Availability:Source code available at http://sbenz.github.com/Paradigm Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics online.


Genome Research | 2011

Assemblathon 1: A competitive assessment of de novo short read assembly methods

Dent Earl; Keith Bradnam; John St. John; Aaron E. Darling; Dawei Lin; Joseph Fass; Hung On Ken Yu; Vince Buffalo; Daniel R. Zerbino; Mark Diekhans; Ngan Nguyen; Pramila Ariyaratne; Wing-Kin Sung; Zemin Ning; Matthias Haimel; Jared T. Simpson; Nuno A. Fonseca; Inanc Birol; T. Roderick Docking; Isaac Ho; Daniel S. Rokhsar; Rayan Chikhi; Dominique Lavenier; Guillaume Chapuis; Delphine Naquin; Nicolas Maillet; Michael C. Schatz; David R. Kelley; Adam M. Phillippy; Sergey Koren

Low-cost short read sequencing technology has revolutionized genomics, though it is only just becoming practical for the high-quality de novo assembly of a novel large genome. We describe the Assemblathon 1 competition, which aimed to comprehensively assess the state of the art in de novo assembly methods when applied to current sequencing technologies. In a collaborative effort, teams were asked to assemble a simulated Illumina HiSeq data set of an unknown, simulated diploid genome. A total of 41 assemblies from 17 different groups were received. Novel haplotype aware assessments of coverage, contiguity, structure, base calling, and copy number were made. We establish that within this benchmark: (1) It is possible to assemble the genome to a high level of coverage and accuracy, and that (2) large differences exist between the assemblies, suggesting room for further improvements in current methods. The simulated benchmark, including the correct answer, the assemblies, and the code that was used to evaluate the assemblies is now public and freely available from http://www.assemblathon.org/.


GigaScience | 2013

Assemblathon 2: evaluating de novo methods of genome assembly in three vertebrate species

Keith Bradnam; Joseph Fass; Anton Alexandrov; Paul Baranay; Michael Bechner; Inanc Birol; Sébastien Boisvert; Jarrod Chapman; Guillaume Chapuis; Rayan Chikhi; Hamidreza Chitsaz; Wen Chi Chou; Jacques Corbeil; Cristian Del Fabbro; Roderick R. Docking; Richard Durbin; Dent Earl; Scott J. Emrich; Pavel Fedotov; Nuno A. Fonseca; Ganeshkumar Ganapathy; Richard A. Gibbs; Sante Gnerre; Élénie Godzaridis; Steve Goldstein; Matthias Haimel; Giles Hall; David Haussler; Joseph Hiatt; Isaac Ho

BackgroundThe 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.ResultsIn 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.ConclusionsMany current genome assemblers produced useful assemblies, containing a significant representation of their genes 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.


Genome Research | 2011

A genome-wide perspective on the evolutionary history of enigmatic wolf-like canids

Bridgett M. vonHoldt; John P. Pollinger; Dent Earl; James C. Knowles; Adam R. Boyko; Heidi G. Parker; Eli Geffen; Malgorzata Pilot; Włodzimierz Jędrzejewski; Bogumiła Jędrzejewska; Vadim E. Sidorovich; Claudia Greco; Ettore Randi; Marco Musiani; Roland Kays; Carlos Bustamante; Elaine A. Ostrander; John Novembre; Robert K. Wayne

High-throughput genotyping technologies developed for model species can potentially increase the resolution of demographic history and ancestry in wild relatives. We use a SNP genotyping microarray developed for the domestic dog to assay variation in over 48K loci in wolf-like species worldwide. Despite the high mobility of these large carnivores, we find distinct hierarchical population units within gray wolves and coyotes that correspond with geographic and ecologic differences among populations. Further, we test controversial theories about the ancestry of the Great Lakes wolf and red wolf using an analysis of haplotype blocks across all 38 canid autosomes. We find that these enigmatic canids are highly admixed varieties derived from gray wolves and coyotes, respectively. This divergent genomic history suggests that they do not have a shared recent ancestry as proposed by previous researchers. Interspecific hybridization, as well as the process of evolutionary divergence, may be responsible for the observed phenotypic distinction of both forms. Such admixture complicates decisions regarding endangered species restoration and protection.


Science | 2014

Three crocodilian genomes reveal ancestral patterns of evolution among archosaurs

Richard E. Green; Edward L. Braun; Joel Armstrong; Dent Earl; Ngan Nguyen; Glenn Hickey; Michael W. Vandewege; John St. John; Salvador Capella-Gutiérrez; Todd A. Castoe; Colin Kern; Matthew K. Fujita; Juan C. Opazo; Jerzy Jurka; Kenji K. Kojima; Juan Caballero; Robert Hubley; Arian Smit; Roy N. Platt; Christine Lavoie; Meganathan P. Ramakodi; John W. Finger; Alexander Suh; Sally R. Isberg; Lee G. Miles; Amanda Y. Chong; Weerachai Jaratlerdsiri; Jaime Gongora; C. Moran; Andrés Iriarte

INTRODUCTION Crocodilians and birds are the two extant clades of archosaurs, a group that includes the extinct dinosaurs and pterosaurs. Fossils suggest that living crocodilians (alligators, crocodiles, and gharials) have a most recent common ancestor 80 to 100 million years ago. Extant crocodilians are notable for their distinct morphology, limited intraspecific variation, and slow karyotype evolution. Despite their unique biology and phylogenetic position, little is known about genome evolution within crocodilians. Evolutionary rates of tetrapods inferred from DNA sequences anchored by ultraconserved elements. Evolutionary rates among reptiles vary, with especially low rates among extant crocodilians but high rates among squamates. We have reconstructed the genomes of the common ancestor of birds and of all archosaurs (shown in gray silhouette, although the morphology of these species is uncertain). RATIONALE Genome sequences for the American alligator, saltwater crocodile, and Indian gharial—representatives of all three extant crocodilian families—were obtained to facilitate better understanding of the unique biology of this group and provide a context for studying avian genome evolution. Sequence data from these three crocodilians and birds also allow reconstruction of the ancestral archosaurian genome. RESULTS We sequenced shotgun genomic libraries from each species and used a variety of assembly strategies to obtain draft genomes for these three crocodilians. The assembled scaffold N50 was highest for the alligator (508 kilobases). Using a panel of reptile genome sequences, we generated phylogenies that confirm the sister relationship between crocodiles and gharials, the relationship with birds as members of extant Archosauria, and the outgroup status of turtles relative to birds and crocodilians. We also estimated evolutionary rates along branches of the tetrapod phylogeny using two approaches: ultraconserved element–anchored sequences and fourfold degenerate sites within stringently filtered orthologous gene alignments. Both analyses indicate that the rates of base substitution along the crocodilian and turtle lineages are extremely low. Supporting observations were made for transposable element content and for gene family evolution. Analysis of whole-genome alignments across a panel of reptiles and mammals showed that the rate of accumulation of micro-insertions and microdeletions is proportionally lower in crocodilians, consistent with a single underlying cause of a reduced rate of evolutionary change rather than intrinsic differences in base repair machinery. We hypothesize that this single cause may be a consistently longer generation time over the evolutionary history of Crocodylia. Low heterozygosity was observed in each genome, consistent with previous analyses, including the Chinese alligator. Pairwise sequential Markov chain analysis of regional heterozygosity indicates that during glacial cycles of the Pleistocene, each species suffered reductions in effective population size. The reduction was especially strong for the American alligator, whose current range extends farthest into regions of temperate climates. CONCLUSION We used crocodilian, avian, and outgroup genomes to reconstruct 584 megabases of the archosaurian common ancestor genome and the genomes of key ancestral nodes. The estimated accuracy of the archosaurian genome reconstruction is 91% and is higher for conserved regions such as genes. The reconstructed genome can be improved by adding more crocodilian and avian genome assemblies and may provide a unique window to the genomes of extinct organisms such as dinosaurs and pterosaurs. To provide context for the diversification of archosaurs—the group that includes crocodilians, dinosaurs, and birds—we generated draft genomes of three crocodilians: Alligator mississippiensis (the American alligator), Crocodylus porosus (the saltwater crocodile), and Gavialis gangeticus (the Indian gharial). We observed an exceptionally slow rate of genome evolution within crocodilians at all levels, including nucleotide substitutions, indels, transposable element content and movement, gene family evolution, and chromosomal synteny. When placed within the context of related taxa including birds and turtles, this suggests that the common ancestor of all of these taxa also exhibited slow genome evolution and that the comparatively rapid evolution is derived in birds. The data also provided the opportunity to analyze heterozygosity in crocodilians, which indicates a likely reduction in population size for all three taxa through the Pleistocene. Finally, these data combined with newly published bird genomes allowed us to reconstruct the partial genome of the common ancestor of archosaurs, thereby providing a tool to investigate the genetic starting material of crocodilians, birds, and dinosaurs.


Genome Biology | 2013

Retrotransposition of gene transcripts leads to structural variation in mammalian genomes.

Adam D. Ewing; Tracy Ballinger; Dent Earl; Christopher C. Harris; Li Ding; Richard Wilson; David Haussler

BackgroundRetroposed processed gene transcripts are an important source of material for new gene formation on evolutionary timescales. Most prior work on gene retrocopy discovery compared copies in reference genome assemblies to their source genes. Here, we explore gene retrocopy insertion polymorphisms (GRIPs) that are present in the germlines of individual humans, mice, and chimpanzees, and we identify novel gene retrocopy insertions in cancerous somatic tissues that are absent from patient-matched non-cancer genomes.ResultsThrough analysis of whole-genome sequence data, we found evidence for 48 GRIPs in the genomes of one or more humans sequenced as part of the 1,000 Genomes Project and The Cancer Genome Atlas, but which were not in the human reference assembly. Similarly, we found evidence for 755 GRIPs at distinct locations in one or more of 17 inbred mouse strains but which were not in the mouse reference assembly, and 19 GRIPs across a cohort of 10 chimpanzee genomes, which were not in the chimpanzee reference genome assembly. Many of these insertions are new members of existing gene families whose source genes are highly and widely expressed, and the majority have detectable hallmarks of processed gene retrocopy formation. We estimate the rate of novel gene retrocopy insertions in humans and chimps at roughly one new gene retrocopy insertion for every 6,000 individuals.ConclusionsWe find that gene retrocopy polymorphisms are a widespread phenomenon, present a multi-species analysis of these events, and provide a method for their ascertainment.


GigaScience | 2013

Assemblathon 2: evaluating de novo

Keith Bradnam; Joseph Fass; Anton Alexandrov; Paul Baranay; Michael Bechner; Inanc Birol; Sébastien Boisvert; Jarrod Chapman; Guillaume Chapuis; Rayan Chikhi; Hamidreza Chitsaz; Wen-Chi Chou; Jacques Corbeil; Cristian Del Fabbro; T. Roderick Docking; Richard Durbin; Dent Earl; Scott J. Emrich; Pavel Fedotov; Nuno A. Fonseca; Ganeshkumar Ganapathy; Richard A. Gibbs; Sante Gnerre; Élénie Godzaridis; Steve Goldstein; Matthias Haimel; Giles Hall; David Haussler; Joseph Hiatt; Isaac Ho

BackgroundThe 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.ResultsIn 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.ConclusionsMany current genome assemblers produced useful assemblies, containing a significant representation of their genes 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.


research in computational molecular biology | 2010

Cactus graphs for genome comparisons

Benedict Paten; Mark Diekhans; Dent Earl; John St. John; Jian Ma; Bernard B. Suh; David Haussler

We introduce a data structure, analysis and visualization scheme called a cactus graph for comparing sets of related genomes Cactus graphs capture some of the advantages of de Bruijn and breakpoint graphs in one unified framework They naturally decompose the common substructures in a set of related genomes into a hierarchy of chains that can be visualized as multiple alignments and nets that can be visualized in circular genome plots.

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David Haussler

University of California

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Benedict Paten

University of California

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Mark Diekhans

University of California

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Joel Armstrong

University of California

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Ngan Nguyen

University of California

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Glenn Hickey

University of California

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Richard Durbin

Wellcome Trust Sanger Institute

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Isaac Ho

United States Department of Energy

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