Author
Vagheesh M. Narasimhan
Other affiliations: Wellcome Trust Sanger Institute, University of Texas at Austin, University of Cambridge
Bio: Vagheesh M. Narasimhan is an academic researcher from Harvard University. The author has contributed to research in topics: Population & Medicine. The author has an hindex of 15, co-authored 19 publications receiving 2796 citations. Previous affiliations of Vagheesh M. Narasimhan include Wellcome Trust Sanger Institute & University of Texas at Austin.
Topics: Population, Medicine, Biology, Ancient DNA, Exome
Papers
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TL;DR: This work presents an approach that uses clade-specific marker genes to unambiguously assign reads to microbial clades more accurately and >50× faster than current approaches, and validated the metagenomic phylogenetic analysis tool, MetaPhlAn, on terabases of short reads.
Abstract: Metagenomic shotgun sequencing data can identify microbes populating a microbial community and their proportions, but existing taxonomic profiling methods are inefficient for increasingly large data sets. We present an approach that uses clade-specific marker genes to unambiguously assign reads to microbial clades more accurately and >50× faster than current approaches. We validated our metagenomic phylogenetic analysis tool, MetaPhlAn, on terabases of short reads and provide the largest metagenomic profiling to date of the human gut. It can be accessed at http://huttenhower.sph.harvard.edu/metaphlan/.
1,566 citations
TL;DR: BCFtools/RoH is presented and evaluated, an extension to the BCFtools software package, that detects regions of autozygosity in sequencing data, in particular exome data, using a hidden Markov model and it is shown that it has higher sensitivity and specificity than existing methods under a range of sequencing error rates and levels of autozykgosity.
Abstract: Summary: Runs of homozygosity (RoHs) are genomic stretches of a diploid genome that show identical alleles on both chromosomes. Longer RoHs are unlikely to have arisen by chance but are likely to denote autozygosity, whereby both copies of the genome descend from the same recent ancestor. Early tools to detect RoH used genotype array data, but substantially more information is available from sequencing data. Here, we present and evaluate BCFtools/RoH, an extension to the BCFtools software package, that detects regions of autozygosity in sequencing data, in particular exome data, using a hidden Markov model. By applying it to simulated data and real data from the 1000 Genomes Project we estimate its accuracy and show that it has higher sensitivity and specificity than existing methods under a range of sequencing error rates and levels of autozygosity.
Availability and implementation: BCFtools/RoH and its associated binary/source files are freely available from https://github.com/samtools/BCFtools.
Contact: ku.ca.regnas@2nv or ku.ca.regnas@3dp
Supplementary information: Supplementary data are available at Bioinformatics online.
452 citations
Harvard University1, Radcliffe Institute for Advanced Study2, Broad Institute3, University of California, Berkeley4, Howard Hughes Medical Institute5, Massachusetts Institute of Technology6, Sapienza University of Rome7, University of Padua8, Queen's University Belfast9, Russian Academy of Sciences10, Al-Farabi University11, University of Pennsylvania12, University College Dublin13, University of Vienna14, Pennsylvania State University15, Max Planck Society16, Centre for Cellular and Molecular Biology17, Birbal Sahni Institute of Palaeobotany18, Emory University19, Centre national de la recherche scientifique20, Kyrgyz National University21, Altai State University22, Academy of Sciences of the Czech Republic23, University of Oxford24, South Ural State University25, Kemerovo State University26, University College London27, Northwest University (China)28, University of Pittsburgh29, Samara State University30, Chelyabinsk State University31, University of Bologna32, Academy of Sciences of Uzbekistan33, University of Winnipeg34, Simon Fraser University35, National Museum of Natural History36, Tomsk State University37, Naturhistorisches Museum38, Národní muzeum39, Hazara University40, Deccan College Post-Graduate and Research Institute41, Pompeu Fabra University42, Hartwick College43, University of California, Santa Barbara44, Washington University in St. Louis45
TL;DR: It is shown that Steppe ancestry then integrated further south in the first half of the second millennium BCE, contributing up to 30% of the ancestry of modern groups in South Asia, supporting the idea that the archaeologically documented dispersal of domesticates was accompanied by the spread of people from multiple centers of domestication.
Abstract: By sequencing 523 ancient humans, we show that the primary source of ancestry in modern South Asians is a prehistoric genetic gradient between people related to early hunter-gatherers of Iran and Southeast Asia. After the Indus Valley Civilization's decline, its people mixed with individuals in the southeast to form one of the two main ancestral populations of South Asia, whose direct descendants live in southern India. Simultaneously, they mixed with descendants of Steppe pastoralists who, starting around 4000 years ago, spread via Central Asia to form the other main ancestral population. The Steppe ancestry in South Asia has the same profile as that in Bronze Age Eastern Europe, tracking a movement of people that affected both regions and that likely spread the distinctive features shared between Indo-Iranian and Balto-Slavic languages.
354 citations
TL;DR: It is found that the two eastern subspecies have experienced a prolonged population decline over the past 100,000 years, resulting in very low genetic diversity and an increased overall burden of deleterious variation.
Abstract: Mountain gorillas are an endangered great ape subspecies and a prominent focus for conservation, yet we know little about their genomic diversity and evolutionary past. We sequenced whole genomes from multiple wild individuals and compared the genomes of all four Gorilla subspecies. We found that the two eastern subspecies have experienced a prolonged population decline over the past 100,000 years, resulting in very low genetic diversity and an increased overall burden of deleterious variation. A further recent decline in the mountain gorilla population has led to extensive inbreeding, such that individuals are typically homozygous at 34% of their sequence, leading to the purging of severely deleterious recessive mutations from the population. We discuss the causes of their decline and the consequences for their future survival.
301 citations
TL;DR: This research presents a novel probabilistic approach that allows us to assess the importance of knowing the carrier and removal status of canine coronavirus, as a source of infection for other animals.
Abstract: Rationale:Vascular smooth muscle cell (VSMC) accumulation is a hallmark of atherosclerosis and vascular injury. However, fundamental aspects of proliferation and the phenotypic changes within indiv...
291 citations
Cited by
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Harvard University1, Broad Institute2, Boston Children's Hospital3, University of Washington4, University of Arizona5, Cardiff University6, Google7, Icahn School of Medicine at Mount Sinai8, Samsung Medical Center9, Vertex Pharmaceuticals10, University of Michigan11, University of Cambridge12, State University of New York Upstate Medical University13, Karolinska Institutet14, University of Eastern Finland15, University of Oxford16, Wellcome Trust Centre for Human Genetics17, Cedars-Sinai Medical Center18, University of Ottawa19, University of Pennsylvania20, University of North Carolina at Chapel Hill21, University of Helsinki22, University of California, San Diego23, University of Mississippi Medical Center24
TL;DR: The aggregation and analysis of high-quality exome (protein-coding region) DNA sequence data for 60,706 individuals of diverse ancestries generated as part of the Exome Aggregation Consortium (ExAC) provides direct evidence for the presence of widespread mutational recurrence.
Abstract: Large-scale reference data sets of human genetic variation are critical for the medical and functional interpretation of DNA sequence changes. Here we describe the aggregation and analysis of high-quality exome (protein-coding region) DNA sequence data for 60,706 individuals of diverse ancestries generated as part of the Exome Aggregation Consortium (ExAC). This catalogue of human genetic diversity contains an average of one variant every eight bases of the exome, and provides direct evidence for the presence of widespread mutational recurrence. We have used this catalogue to calculate objective metrics of pathogenicity for sequence variants, and to identify genes subject to strong selection against various classes of mutation; identifying 3,230 genes with near-complete depletion of predicted protein-truncating variants, with 72% of these genes having no currently established human disease phenotype. Finally, we demonstrate that these data can be used for the efficient filtering of candidate disease-causing variants, and for the discovery of human 'knockout' variants in protein-coding genes.
8,758 citations
TL;DR: The Human Microbiome Project Consortium reported the first results of their analysis of microbial communities from distinct, clinically relevant body habitats in a human cohort; the insights into the microbial communities of a healthy population lay foundations for future exploration of the epidemiology, ecology and translational applications of the human microbiome as discussed by the authors.
Abstract: The Human Microbiome Project Consortium reports the first results of their analysis of microbial communities from distinct, clinically relevant body habitats in a human cohort; the insights into the microbial communities of a healthy population lay foundations for future exploration of the epidemiology, ecology and translational applications of the human microbiome.
8,410 citations
Journal Article•
TL;DR: The Human Microbiome Project has analysed the largest cohort and set of distinct, clinically relevant body habitats so far, finding the diversity and abundance of each habitat’s signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals.
Abstract: Studies of the human microbiome have revealed that even healthy individuals differ remarkably in the microbes that occupy habitats such as the gut, skin and vagina. Much of this diversity remains unexplained, although diet, environment, host genetics and early microbial exposure have all been implicated. Accordingly, to characterize the ecology of human-associated microbial communities, the Human Microbiome Project has analysed the largest cohort and set of distinct, clinically relevant body habitats so far. We found the diversity and abundance of each habitat’s signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals. The project encountered an estimated 81–99% of the genera, enzyme families and community configurations occupied by the healthy Western microbiome. Metagenomic carriage of metabolic pathways was stable among individuals despite variation in community structure, and ethnic/racial background proved to be one of the strongest associations of both pathways and microbes with clinical metadata. These results thus delineate the range of structural and functional configurations normal in the microbial communities of a healthy population, enabling future characterization of the epidemiology, ecology and translational applications of the human microbiome.
6,350 citations
01 Aug 2000
TL;DR: Assessment of medical technology in the context of commercialization with Bioentrepreneur course, which addresses many issues unique to biomedical products.
Abstract: BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.
4,833 citations
01 Feb 2015
TL;DR: In this article, the authors describe the integrative analysis of 111 reference human epigenomes generated as part of the NIH Roadmap Epigenomics Consortium, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression.
Abstract: The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.
4,409 citations