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Richard K. Wilson

Bio: Richard K. Wilson is an academic researcher from Nationwide Children's Hospital. The author has contributed to research in topics: Genome & Gene. The author has an hindex of 173, co-authored 463 publications receiving 260000 citations. Previous affiliations of Richard K. Wilson include University of Washington & St. Jude Children's Research Hospital.
Topics: Genome, Gene, Exome sequencing, Genomics, Human genome


Papers
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Journal ArticleDOI
TL;DR: The frequency of cancer diagnoses and leukemia subtypes in children and adults and the genetic landscape of 15 different types of pediatric cancers determined from whole-genome sequencing of 260 tumors and matching germline samples are presented.
Abstract: Subject terms: Cancer genomics• Paediatric cancer• Sequencing At a glance Figures View all figures Figure 1: Frequency of cancer diagnoses and leukemia subtypes in children and adults. (a) The frequency of cancer types in children (left) and adults (right) on the basis of 2012 Surveillance, Epidemiology and End Results (SEER) data. Each chart is organized with cancers listed from the most common to the least common in a clockwise fashion. (b) The frequency of T-cell lineage (blue text) and B-cell lineage (black text) subtypes of acute lymphoblastic leukemia (ALL) in children (left) and adults (right). Each chart is organized with ALL subtypes listed from the most common to the least common in a clockwise fashion. iAMP21, intrachromosomal amplification of chromosome 21. Full size image View in article Figure 2: Genetic landscape of 15 different types of pediatric cancers determined from whole-genome sequencing of 260 tumors and matching germline samples. The number of somatic mutations in each sample, including single-nucleotide variations (SNVs), insertion and/or deletion events (indels) and structural variations, is shown as the height in the three-dimensional graph. Only high-quality variations or validated somatic mutations are included in the summary. CDS, protein-coding regions; tier 1, mutations in annotated genes; tier 2, mutations in non-coding conserved or regulatory regions; tier 3, mutations in non-repetitive, non-coding and non-conserved regions; tier 4, mutations in repetitive regions. Tier 2 and tier 3/tier 4 mutations were rescaled to 1/10 and 1/100 of the original counts to maintain a consistent scale with the results for other somatic lesions. INF, infant ALL; CBF, core-binding-factor acute myeloid leukemia; TALL, T-cell ALL; AMLM7, acute megakaryoblastic leukemia; HYPO, hypodiploid ALL; PHALL, Philadelphia chromosome–positive BCR-ABL1 ALL; RB, retinoblastoma; RHB, rhabdomyosarcoma; NBL, neuroblastoma; OS, osteosarcoma; ACT, adrenocortical carcinoma; HGG, high-grade glioblastoma; LGG, low-grade glioma; EPD, ependymoma; MB, medulloblastoma. Full size image View in article

317 citations

Journal ArticleDOI
TL;DR: Common vertebrate regulatory networks, some of which have analogs in human diseases, are often involved in the western painted turtle's extraordinary physiological capacities, and may offer important insights into the management of a number of human health disorders.
Abstract: Background: We describe the genome of the western painted turtle, Chrysemys picta bellii, one of the most widespread, abundant, and well-studied turtles. We place the genome into a comparative evolutionary context, and focus on genomic features associated with tooth loss, immune function, longevity, sex differentiation and determination, and the species’ physiological capacities to withstand extreme anoxia and tissue freezing. Results: Our phylogenetic analyses confirm that turtles are the sister group to living archosaurs, and demonstrate an extraordinarily slow rate of sequence evolution in the painted turtle. The ability of the painted turtle to withstand complete anoxia and partial freezing appears to be associated with common vertebrate gene networks, and we identify candidate genes for future functional analyses. Tooth loss shares a common pattern of pseudogenization and degradation of tooth-specific genes with birds, although the rate of accumulation of mutations is much slower in the painted turtle. Genes associated with sex differentiation generally reflect phylogeny rather than convergence in sex determination functionality. Among gene families that demonstrate exceptional expansions or show signatures of strong natural selection, immune function and musculoskeletal patterning genes are consistently over-represented. Conclusions: Our comparative genomic analyses indicate that common vertebrate regulatory networks, some of which have analogs in human diseases, are often involved in the western painted turtle’s extraordinary physiological capacities. As these regulatory pathways are analyzed at the functional level, the painted turtle may offer important insights into the management of a number of human health disorders.

307 citations

Journal ArticleDOI
TL;DR: A draft genome sequence of Trichinella spiralis, a food-borne zoonotic parasite, which is the most common cause of human trichinellosis is reported, enabling identification of archetypical genes and molecular signatures exclusive to nematodes.
Abstract: Genome evolution studies for the phylum Nematoda have been limited by focusing on comparisons involving Caenorhabditis elegans We report a draft genome sequence of Trichinella spiralis, a food-borne zoonotic parasite, which is the most common cause of human trichinellosis This parasitic nematode is an extant member of a clade that diverged early in the evolution of the phylum, enabling identification of archetypical genes and molecular signatures exclusive to nematodes We sequenced the 64-Mb nuclear genome, which is estimated to contain 15,808 protein-coding genes, at ∼35-fold coverage using whole-genome shotgun and hierarchal map-assisted sequencing Comparative genome analyses support intrachromosomal rearrangements across the phylum, disproportionate numbers of protein family deaths over births in parasitic compared to a non-parasitic nematode and a preponderance of gene-loss and -gain events in nematodes relative to Drosophila melanogaster This genome sequence and the identified pan-phylum characteristics will contribute to genome evolution studies of Nematoda as well as strategies to combat global parasites of humans, food animals and crops

297 citations

Journal ArticleDOI
Rafael D. Mesquita1, Raquel J. Vionette-Amaral1, Carl Lowenberger2, Rolando Rivera-Pomar3, Fernando A. Monteiro4, Fernando A. Monteiro1, Patrick Minx5, John Spieth5, A. Bernardo Carvalho1, Francisco Panzera6, Daniel Lawson7, André Q. Torres4, André Q. Torres1, José M. C. Ribeiro8, Marcos Henrique Ferreira Sorgine1, Robert M. Waterhouse, Michael J. Montague5, Fernando Abad-Franch4, Michele Alves-Bezerra1, Laurence Rodrigues do Amaral9, Helena Araujo1, Ricardo Nascimento Araújo1, Ricardo Nascimento Araújo10, L. Aravind8, Georgia C. Atella1, Patrícia Azambuja1, Patrícia Azambuja4, Mateus Berni1, Paula R. Bittencourt-Cunha1, Glória R.C. Braz1, Gustavo M. Calderón-Fernández3, Claudia M. A. Carareto11, Mikkel B. Christensen7, Igor Rodrigues da Costa1, Samara G. da Costa4, Marilvia Dansa12, Carlos R. O. Daumas-Filho1, Iron F. De-Paula1, Felipe A. Dias1, George Dimopoulos13, Scott J. Emrich14, Natalia Esponda-Behrens3, Patrícia Fampa15, Rita D. Fernandez-Medina4, Rodrigo Nunes da Fonseca1, Marcio Fontenele1, Catrina Fronick5, Lucinda Fulton5, Ana Caroline P. Gandara1, Eloi S. Garcia1, Eloi S. Garcia4, Fernando A. Genta1, Fernando A. Genta4, Gloria I. Giraldo-Calderón14, Bruno Gomes1, Bruno Gomes4, Katia C. Gondim1, Adriana Granzotto11, Alessandra A. Guarneri4, Alessandra A. Guarneri1, Roderic Guigó16, Myriam Harry17, Daniel S.T. Hughes7, Willy Jablonka1, Emmanuelle Jacquin-Joly, M. Patricia Juárez3, Leonardo Koerich1, Angela B. Lange18, Jose Manuel Latorre-Estivalis4, Jose Manuel Latorre-Estivalis1, Andrés Lavore3, Gena G. Lawrence18, Gena G. Lawrence19, Cristiano Lazoski1, Claudio R. Lazzari17, Raphael R.S. Lopes1, Marcelo G. Lorenzo4, Marcelo G. Lorenzo1, Magda D. Lugon12, David Majerowicz1, Paula L. Marcet19, Marco Mariotti16, Hatisaburo Masuda1, Karyn Megy7, Ana C.A. Melo1, Fanis Missirlis20, Theo Mota10, Fernando G. Noriega21, Marcela Nouzova21, Rodrigo Dutra Nunes1, Raquel L.L. Oliveira1, Gilbert Oliveira-Silveira1, Sheila Ons3, Ian Orchard18, Lucia Pagola3, Gabriela O. Paiva-Silva1, Agustina Pascual3, Márcio G. Pavan4, Nicolás Pedrini3, Alexandre A. Peixoto4, Alexandre A. Peixoto1, Marcos H. Pereira10, Marcos H. Pereira1, Andrew Pike13, Carla Polycarpo1, Francisco Prosdocimi1, Rodrigo Ribeiro-Rodrigues22, Hugh M. Robertson23, Ana Paula Salerno, Didier Salmon1, Didac Santesmasses16, Renata Schama4, Renata Schama1, Eloy S. Seabra-Junior, Lívia Silva-Cardoso1, Mário A.C. Silva-Neto1, Matheus Souza-Gomes9, Marcos Sterkel1, Mabel L. Taracena1, Marta Tojo24, Zhijian Jake Tu25, Jose M. C. Tubio26, Raul Ursic-Bedoya2, Thiago M. Venancio12, Thiago M. Venancio1, Ana Beatriz Walter-Nuno1, Derek Wilson7, Wesley C. Warren5, Richard K. Wilson5, Erwin Huebner27, Ellen M. Dotson19, Pedro L. Oliveira1 
TL;DR: The first genome sequence of a nondipteran insect vector of an important human parasitic disease is described, which provides critical information on the physiology and evolution of this important vector species and should be instrumental for the development of innovative disease control methods.
Abstract: Rhodnius prolixus not only has served as a model organism for the study of insect physiology, but also is a major vector of Chagas disease, an illness that affects approximately seven million people worldwide. We sequenced the genome of R. prolixus, generated assembled sequences covering 95% of the genome (∼ 702 Mb), including 15,456 putative protein-coding genes, and completed comprehensive genomic analyses of this obligate blood-feeding insect. Although immune-deficiency (IMD)-mediated immune responses were observed, R. prolixus putatively lacks key components of the IMD pathway, suggesting a reorganization of the canonical immune signaling network. Although both Toll and IMD effectors controlled intestinal microbiota, neither affected Trypanosoma cruzi, the causal agent of Chagas disease, implying the existence of evasion or tolerance mechanisms. R. prolixus has experienced an extensive loss of selenoprotein genes, with its repertoire reduced to only two proteins, one of which is a selenocysteine-based glutathione peroxidase, the first found in insects. The genome contained actively transcribed, horizontally transferred genes from Wolbachia sp., which showed evidence of codon use evolution toward the insect use pattern. Comparative protein analyses revealed many lineage-specific expansions and putative gene absences in R. prolixus, including tandem expansions of genes related to chemoreception, feeding, and digestion that possibly contributed to the evolution of a blood-feeding lifestyle. The genome assembly and these associated analyses provide critical information on the physiology and evolution of this important vector species and should be instrumental for the development of innovative disease control methods.

293 citations

Journal ArticleDOI
25 Aug 2015-JAMA
TL;DR: The detection of persistent leukemia-associated mutations in at least 5% of bone marrow cells in day 30 remission samples was associated with a significantly increased risk of relapse, and reduced overall survival.
Abstract: Importance Tests that predict outcomes for patients with acute myeloid leukemia (AML) are imprecise, especially for those with intermediate risk AML. Objectives To determine whether genomic approaches can provide novel prognostic information for adult patients with de novo AML. Design, Setting, and Participants Whole-genome or exome sequencing was performed on samples obtained at disease presentation from 71 patients with AML (mean age, 50.8 years) treated with standard induction chemotherapy at a single site starting in March 2002, with follow-up through January 2015. In addition, deep digital sequencing was performed on paired diagnosis and remission samples from 50 patients (including 32 with intermediate-risk AML), approximately 30 days after successful induction therapy. Twenty-five of the 50 were from the cohort of 71 patients, and 25 were new, additional cases. Exposures Whole-genome or exome sequencing and targeted deep sequencing. Risk of identification based on genetic data. Main Outcomes and Measures Mutation patterns (including clearance of leukemia-associated variants after chemotherapy) and their association with event-free survival and overall survival. Results Analysis of comprehensive genomic data from the 71 patients did not improve outcome assessment over current standard-of-care metrics. In an analysis of 50 patients with both presentation and documented remission samples, 24 (48%) had persistent leukemia-associated mutations in at least 5% of bone marrow cells at remission. The 24 with persistent mutations had significantly reduced event-free survival vs the 26 who cleared all mutations (median [95% CI]: 6.0 months [95% CI, 3.7-9.6] for persistent mutations vs 17.9 months [95% CI, 11.3-40.4] for cleared mutations, log-rank P P P = .003; HR, 2.86 [95% CI, 1.39-5.88], P = .004). Among the 32 patients with intermediate cytogenetic risk, the 14 patients with persistent mutations had reduced event-free survival compared with the 18 patients who cleared all mutations (median [95% CI]: 8.8 months [95% CI, 3.7-14.6] for persistent mutations vs 25.6 months [95% CI, 11.4-not estimable] for cleared mutations, log-rank P = .003; HR, 3.32 [95% CI, 1.44-7.67], P = .005) and reduced overall survival (median [95% CI]: 19.3 months [95% CI, 7.5-42.3] for persistent mutations vs 46.8 months [95% CI, 22.6-not estimable] for cleared mutations, log-rank P = .02; HR, 2.88 [95% CI, 1.11-7.45], P = .03). Conclusions and Relevance The detection of persistent leukemia-associated mutations in at least 5% of bone marrow cells in day 30 remission samples was associated with a significantly increased risk of relapse, and reduced overall survival. These data suggest that this genomic approach may improve risk stratification for patients with AML.

292 citations


Cited by
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Journal ArticleDOI
TL;DR: A new criterion for triggering the extension of word hits, combined with a new heuristic for generating gapped alignments, yields a gapped BLAST program that runs at approximately three times the speed of the original.
Abstract: The BLAST programs are widely used tools for searching protein and DNA databases for sequence similarities. For protein comparisons, a variety of definitional, algorithmic and statistical refinements described here permits the execution time of the BLAST programs to be decreased substantially while enhancing their sensitivity to weak similarities. A new criterion for triggering the extension of word hits, combined with a new heuristic for generating gapped alignments, yields a gapped BLAST program that runs at approximately three times the speed of the original. In addition, a method is introduced for automatically combining statistically significant alignments produced by BLAST into a position-specific score matrix, and searching the database using this matrix. The resulting Position-Specific Iterated BLAST (PSIBLAST) program runs at approximately the same speed per iteration as gapped BLAST, but in many cases is much more sensitive to weak but biologically relevant sequence similarities. PSI-BLAST is used to uncover several new and interesting members of the BRCT superfamily.

70,111 citations

Journal ArticleDOI
Eric S. Lander1, Lauren Linton1, Bruce W. Birren1, Chad Nusbaum1  +245 moreInstitutions (29)
15 Feb 2001-Nature
TL;DR: The results of an international collaboration to produce and make freely available a draft sequence of the human genome are reported and an initial analysis is presented, describing some of the insights that can be gleaned from the sequence.
Abstract: The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.

22,269 citations

Journal ArticleDOI
TL;DR: The GATK programming framework enables developers and analysts to quickly and easily write efficient and robust NGS tools, many of which have already been incorporated into large-scale sequencing projects like the 1000 Genomes Project and The Cancer Genome Atlas.
Abstract: Next-generation DNA sequencing (NGS) projects, such as the 1000 Genomes Project, are already revolutionizing our understanding of genetic variation among individuals. However, the massive data sets generated by NGS—the 1000 Genome pilot alone includes nearly five terabases—make writing feature-rich, efficient, and robust analysis tools difficult for even computationally sophisticated individuals. Indeed, many professionals are limited in the scope and the ease with which they can answer scientific questions by the complexity of accessing and manipulating the data produced by these machines. Here, we discuss our Genome Analysis Toolkit (GATK), a structured programming framework designed to ease the development of efficient and robust analysis tools for next-generation DNA sequencers using the functional programming philosophy of MapReduce. The GATK provides a small but rich set of data access patterns that encompass the majority of analysis tool needs. Separating specific analysis calculations from common data management infrastructure enables us to optimize the GATK framework for correctness, stability, and CPU and memory efficiency and to enable distributed and shared memory parallelization. We highlight the capabilities of the GATK by describing the implementation and application of robust, scale-tolerant tools like coverage calculators and single nucleotide polymorphism (SNP) calling. We conclude that the GATK programming framework enables developers and analysts to quickly and easily write efficient and robust NGS tools, many of which have already been incorporated into large-scale sequencing projects like the 1000 Genomes Project and The Cancer Genome Atlas.

20,557 citations

Journal ArticleDOI
TL;DR: Bowtie extends previous Burrows-Wheeler techniques with a novel quality-aware backtracking algorithm that permits mismatches and can be used simultaneously to achieve even greater alignment speeds.
Abstract: Bowtie is an ultrafast, memory-efficient alignment program for aligning short DNA sequence reads to large genomes. For the human genome, Burrows-Wheeler indexing allows Bowtie to align more than 25 million reads per CPU hour with a memory footprint of approximately 1.3 gigabytes. Bowtie extends previous Burrows-Wheeler techniques with a novel quality-aware backtracking algorithm that permits mismatches. Multiple processor cores can be used simultaneously to achieve even greater alignment speeds. Bowtie is open source http://bowtie.cbcb.umd.edu.

20,335 citations

28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

18,940 citations