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Wellcome Trust Sanger Institute

NonprofitCambridge, 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.


Papers
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Journal ArticleDOI
TL;DR: Genes underlying prominent features of trypanosome biology are highlighted, including the constitutive emphasis on post-transcriptional gene expression control, the importance of flagellar motility and glycolysis in the bloodstream, and of carboxylic acid metabolism and phosphorylation during differentiation from the bloodstream to the insect stage.
Abstract: African trypanosomes are major pathogens of humans and livestock and represent a model for studies of unusual protozoal biology. We describe a high-throughput phenotyping approach termed RNA interference (RNAi) target sequencing, or RIT-seq that, using Illumina sequencing, maps fitness-costs associated with RNAi. We scored the abundance of >90,000 integrated RNAi targets recovered from trypanosome libraries before and after induction of RNAi. Data are presented for 7435 protein coding sequences, >99% of a non-redundant set in the Trypanosoma brucei genome. Analysis of bloodstream and insect life-cycle stages and differentiated libraries revealed genome-scale knockdown profiles of growth and development, linking thousands of previously uncharacterized and "hypothetical" genes to essential functions. Genes underlying prominent features of trypanosome biology are highlighted, including the constitutive emphasis on post-transcriptional gene expression control, the importance of flagellar motility and glycolysis in the bloodstream, and of carboxylic acid metabolism and phosphorylation during differentiation from the bloodstream to the insect stage. The current data set also provides much needed genetic validation to identify new drug targets. RIT-seq represents a versatile new tool for genome-scale functional analyses and for the exploitation of genome sequence data.

428 citations

Journal ArticleDOI
TL;DR: A thorough understanding of DDR pathway complexities must be combined with strategies and lessons learned from the successful registration of PARP inhibitors in order to fully exploit the potential of DDR inhibitors and to ensure their long-term clinical success.
Abstract: J.S. Brown, B. O'Carrigan, and T.A. Yap acknowledge support from the Experimental Cancer Medicine Centre (to The Institute of Cancer Research) and the National Institute for Health Research Biomedical Research Centre (jointly to the Royal Marsden NHS Foundation Trust and The Institute of Cancer Research). Research in The Jackson laboratory is funded by Cancer Research UK (CRUK) program grant number C6/A18796. Core funding is provided by CRUK (C6946/A14492) and the Wellcome Trust (WT092096). S.P. Jackson receives his salary from the University of Cambridge, UK, supplemented by CRUK.

427 citations

Journal ArticleDOI
TL;DR: The recent sequencing of seven strains of S. aureus provides unprecedented information about its genome diversity, and dramatic differences in the carriage and spread of accessory genes, including those involved in virulence and resistance, contribute to the emergence of new strains with healthcare implications.

426 citations

Journal ArticleDOI
TL;DR: ABACAS is intended as a tool to rapidly contiguate (align, order, orientate), visualize and design primers to close gaps on shotgun assembled contigs based on a reference sequence.
Abstract: Summary: Due to the availability of new sequencing technologies, we are now increasingly interested in sequencing closely related strains of existing finished genomes. Recently a number of de novo and mapping-based assemblers have been developed to produce high quality draft genomes from new sequencing technology reads. New tools are necessary to take contigs from a draft assembly through to a fully contiguated genome sequence. ABACAS is intended as a tool to rapidly contiguate (align, order, orientate), visualize and design primers to close gaps on shotgun assembled contigs based on a reference sequence. The input to ABACAS is a set of contigs which will be aligned to the reference genome, ordered and orientated, visualized in the ACT comparative browser, and optimal primer sequences are automatically generated. Availability and Implementation: ABACAS is implemented in Perl and is freely available for download from http://abacas.sourceforge.net Contact: ku.ca.regnas@4as

426 citations

Journal ArticleDOI
Christian Gieger, Aparna Radhakrishnan1, Ana Cvejic1, Weihong Tang2  +159 moreInstitutions (46)
08 Dec 2011-Nature
TL;DR: A high-powered meta-analysis of genome-wide association studies (GWAS) in up to 66,867 individuals of European ancestry is carried out, identifying 68 genomic loci reliably associated with platelet count and volume mapping to established and putative novel regulators of megakaryopoiesis and platelet formation.
Abstract: Platelets are the second most abundant cell type in blood and are essential for maintaining haemostasis. Their count and volume are tightly controlled within narrow physiological ranges, but there is only limited understanding of the molecular processes controlling both traits. Here we carried out a high-powered meta-analysis of genome-wide association studies (GWAS) in up to 66,867 individuals of European ancestry, followed by extensive biological and functional assessment. We identified 68 genomic loci reliably associated with platelet count and volume mapping to established and putative novel regulators of megakaryopoiesis and platelet formation. These genes show megakaryocyte-specific gene expression patterns and extensive network connectivity. Using gene silencing in Danio rerio and Drosophila melanogaster, we identified 11 of the genes as novel regulators of blood cell formation. Taken together, our findings advance understanding of novel gene functions controlling fate-determining events during megakaryopoiesis and platelet formation, providing a new example of successful translation of GWAS to function.

424 citations


Authors

Showing all 4058 results

NameH-indexPapersCitations
Nicholas J. Wareham2121657204896
Gonçalo R. Abecasis179595230323
Panos Deloukas162410154018
Michael R. Stratton161443142586
David W. Johnson1602714140778
Michael John Owen1601110135795
Naveed Sattar1551326116368
Robert E. W. Hancock15277588481
Julian Parkhill149759104736
Nilesh J. Samani149779113545
Michael Conlon O'Donovan142736118857
Jian Yang1421818111166
Christof Koch141712105221
Andrew G. Clark140823123333
Stylianos E. Antonarakis13874693605
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202317
202270
2021836
2020810
2019854
2018764