Institution
Wellcome Trust Sanger Institute
Nonprofit•Cambridge, United Kingdom•
About: Wellcome Trust Sanger Institute is a nonprofit organization based out in Cambridge, United Kingdom. It is known for research contribution in the topics: Population & Genome. The organization has 4009 authors who have published 9671 publications receiving 1224479 citations.
Topics: Population, Genome, Gene, Genome-wide association study, Genomics
Papers published on a yearly basis
Papers
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University of Porto1, Science for Life Laboratory2, Norwich University3, Massachusetts Institute of Technology4, Max Planck Society5, Swedish University of Agricultural Sciences6, Ain Shams University7, Wellcome Trust Sanger Institute8, European Bioinformatics Institute9, University of Cambridge10, Institut national de la recherche agronomique11, University of Bologna12, National Institutes of Health13, United States Department of Energy14, Spanish National Research Council15, University of Montana16, Texas A&M University17
TL;DR: It is proposed that because of a truly complex genetic background, tame behavior in rabbits and other domestic animals evolved by shifts in allele frequencies at many loci, rather than by critical changes at only a few domestication loci.
Abstract: The genetic changes underlying the initial steps of animal domestication are still poorly understood. We generated a high-quality reference genome for the rabbit and compared it to resequencing data from populations of wild and domestic rabbits. We identified more than 100 selective sweeps specific to domestic rabbits but only a relatively small number of fixed (or nearly fixed) single-nucleotide polymorphisms (SNPs) for derived alleles. SNPs with marked allele frequency differences between wild and domestic rabbits were enriched for conserved noncoding sites. Enrichment analyses suggest that genes affecting brain and neuronal development have often been targeted during domestication. We propose that because of a truly complex genetic background, tame behavior in rabbits and other domestic animals evolved by shifts in allele frequencies at many loci, rather than by critical changes at only a few domestication loci.
328 citations
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TL;DR: A strategy that can be used to explore the origin of cancer-associated mutational signatures is developed and it is found that mutation accumulation in organoids deficient in the mismatch repair gene MLH1 is driven by replication errors and accurately models the mutation profiles observed in mismatch repair–deficient colorectal cancers.
Abstract: Mutational processes underlie cancer initiation and progression. Signatures of these processes in cancer genomes may explain cancer etiology and could hold diagnostic and prognostic value. We developed a strategy that can be used to explore the origin of cancer-associated mutational signatures. We used CRISPR-Cas9 technology to delete key DNA repair genes in human colon organoids, followed by delayed subcloning and whole-genome sequencing. We found that mutation accumulation in organoids deficient in the mismatch repair gene MLH1 is driven by replication errors and accurately models the mutation profiles observed in mismatch repair–deficient colorectal cancers. Application of this strategy to the cancer predisposition gene NTHL1, which encodes a base excision repair protein, revealed a mutational footprint (signature 30) previously observed in a breast cancer cohort. We show that signature 30 can arise from germline NTHL1 mutations.
327 citations
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TL;DR: This work presents a method, SoupX, for quantifying the extent of the contamination and estimating “background corrected”, cell expression profiles that can be integrated with existing downstream analysis tools and shows that the application of this method reduces batch effects, strengthens cell-specific quality control and improves biological interpretation.
Abstract: Droplet based single cell RNA sequence analyses assume all acquired RNAs are endogenous to cells. However, any cell free RNAs contained within the input solution are also captured by these assays. This sequencing of cell free RNA constitutes a background contamination that has the potential to confound the correct biological interpretation of single cell transcriptomic data. Here, we demonstrate that contamination from this "soup" of cell free RNAs is ubiquitous, experiment specific in its composition and magnitude, and can lead to erroneous biological conclusions. We present a method, SoupX, for quantifying the extent of the contamination and estimating "background corrected", cell expression profiles that can be integrated with existing downstream analysis tools. We apply this method to two data-sets and show that the application of this method reduces batch effects, strengthens cell-specific quality control and improves biological interpretation.
327 citations
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01 Dec 2016TL;DR: Kaptive, a novel software tool that automates the process of identifying K-loci based on full locus information extracted from whole genome sequences, is introduced, highlighting the extensive diversity of Klebsiella K- loci and the proteins that they encode.
Abstract: Klebsiella pneumoniae is a growing cause of healthcare-associated infections for which multi-drug resistance is a concern. Its polysaccharide capsule is a major virulence determinant and epidemiological marker. However, little is known about capsule epidemiology since serological typing is not widely accessible and many isolates are serologically non-typeable. Molecular typing techniques provide useful insights, but existing methods fail to take full advantage of the information in whole genome sequences. We investigated the diversity of the capsule synthesis loci (K-loci) among 2503 K. pneumoniae genomes. We incorporated analyses of full-length K-locus nucleotide sequences and also clustered protein-encoding sequences to identify, annotate and compare K-locus structures. We propose a standardized nomenclature for K-loci and present a curated reference database. A total of 134 distinct K-loci were identified, including 31 novel types. Comparative analyses indicated 508 unique protein-encoding gene clusters that appear to reassort via homologous recombination. Extensive intra- and inter-locus nucleotide diversity was detected among the wzi and wzc genes, indicating that current molecular typing schemes based on these genes are inadequate. As a solution, we introduce Kaptive, a novel software tool that automates the process of identifying K-loci based on full locus information extracted from whole genome sequences (https://github.com/katholt/Kaptive). This work highlights the extensive diversity of Klebsiella K-loci and the proteins that they encode. The nomenclature, reference database and novel typing method presented here will become essential resources for genomic surveillance and epidemiological investigations of this pathogen.
325 citations
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University of Tartu1, Estonian Biocentre2, University of Cambridge3, University of California, Berkeley4, Arizona State University5, Armenian National Academy of Sciences6, Russian Academy of Sciences7, University of Auckland8, Pennsylvania State University9, University of Winchester10, Wellcome Trust Sanger Institute11, University of Copenhagen12, Bashkir State University13, Kazan Federal University14, Georgia Institute of Technology15, University of Pennsylvania16, Centre national de la recherche scientifique17, Eijkman Institute for Molecular Biology18, Massey University19, University of Dhaka20, Aarhus University21, Griffith University22, Josip Juraj Strossmayer University of Osijek23, Academy of Sciences of Uzbekistan24, Kuban State Medical University25, L.N.Gumilyov Eurasian National University26, Nazarbayev University27, North-Eastern Federal University28, Academy of Medical Sciences, United Kingdom29, Anthony Nolan30, University College London31, University of St Andrews32, University of Kharkiv33, International Burch University34, National Academy of Sciences of Belarus35, Radboud University Nijmegen36, King Abdullah University of Science and Technology37, Stanford University38, University of Arizona39, Stony Brook University40, University Hospital of North Norway41, Estonian Academy of Sciences42
TL;DR: A study of 456 geographically diverse high-coverage Y chromosome sequences, including 299 newly reported samples, infer a second strong bottleneck in Y-chromosome lineages dating to the last 10 ky, and hypothesize that this bottleneck is caused by cultural changes affecting variance of reproductive success among males.
Abstract: It is commonly thought that human genetic diversity in non-African populations was shaped primarily by an out-of-Africa dispersal 50-100 thousand yr ago (kya). Here, we present a study of 456 geographically diverse high-coverage Y chromosome sequences, including 299 newly reported samples. Applying ancient DNA calibration, we date the Y-chromosomal most recent common ancestor (MRCA) in Africa at 254 (95% CI 192-307) kya and detect a cluster of major non-African founder haplogroups in a narrow time interval at 47-52 kya, consistent with a rapid initial colonization model of Eurasia and Oceania after the out-of-Africa bottleneck. In contrast to demographic reconstructions based on mtDNA, we infer a second strong bottleneck in Y-chromosome lineages dating to the last 10 ky. We hypothesize that this bottleneck is caused by cultural changes affecting variance of reproductive success among males.
325 citations
Authors
Showing all 4058 results
Name | H-index | Papers | Citations |
---|---|---|---|
Nicholas J. Wareham | 212 | 1657 | 204896 |
Gonçalo R. Abecasis | 179 | 595 | 230323 |
Panos Deloukas | 162 | 410 | 154018 |
Michael R. Stratton | 161 | 443 | 142586 |
David W. Johnson | 160 | 2714 | 140778 |
Michael John Owen | 160 | 1110 | 135795 |
Naveed Sattar | 155 | 1326 | 116368 |
Robert E. W. Hancock | 152 | 775 | 88481 |
Julian Parkhill | 149 | 759 | 104736 |
Nilesh J. Samani | 149 | 779 | 113545 |
Michael Conlon O'Donovan | 142 | 736 | 118857 |
Jian Yang | 142 | 1818 | 111166 |
Christof Koch | 141 | 712 | 105221 |
Andrew G. Clark | 140 | 823 | 123333 |
Stylianos E. Antonarakis | 138 | 746 | 93605 |