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Institution

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
19 Mar 2009-Nature
TL;DR: Rather than one or two domestication events leading to the extant baker’s yeasts, the population structure of S. cerevisiae consists of a few well-defined, geographically isolated lineages and many different mosaics of these lineages, supporting the idea that human influence provided the opportunity for cross-breeding and production of new combinations of pre-existing variations.
Abstract: Since the completion of the genome sequence of Saccharomyces cerevisiae in 1996 (refs 1, 2), there has been a large increase in complete genome sequences, accompanied by great advances in our understanding of genome evolution. Although little is known about the natural and life histories of yeasts in the wild, there are an increasing number of studies looking at ecological and geographic distributions, population structure and sexual versus asexual reproduction. Less well understood at the whole genome level are the evolutionary processes acting within populations and species that lead to adaptation to different environments, phenotypic differences and reproductive isolation. Here we present one- to fourfold or more coverage of the genome sequences of over seventy isolates of the baker's yeast S. cerevisiae and its closest relative, Saccharomyces paradoxus. We examine variation in gene content, single nucleotide polymorphisms, nucleotide insertions and deletions, copy numbers and transposable elements. We find that phenotypic variation broadly correlates with global genome-wide phylogenetic relationships. S. paradoxus populations are well delineated along geographic boundaries, whereas the variation among worldwide S. cerevisiae isolates shows less differentiation and is comparable to a single S. paradoxus population. Rather than one or two domestication events leading to the extant baker's yeasts, the population structure of S. cerevisiae consists of a few well-defined, geographically isolated lineages and many different mosaics of these lineages, supporting the idea that human influence provided the opportunity for cross-breeding and production of new combinations of pre-existing variations.

1,425 citations

Journal ArticleDOI
TL;DR: This work presents a strategy for batch correction based on the detection of mutual nearest neighbors (MNNs) in the high-dimensional expression space and demonstrates the superiority of this approach compared with existing methods by using both simulated and real scRNA-seq data sets.
Abstract: Large-scale single-cell RNA sequencing (scRNA-seq) data sets that are produced in different laboratories and at different times contain batch effects that may compromise the integration and interpretation of the data. Existing scRNA-seq analysis methods incorrectly assume that the composition of cell populations is either known or identical across batches. We present a strategy for batch correction based on the detection of mutual nearest neighbors (MNNs) in the high-dimensional expression space. Our approach does not rely on predefined or equal population compositions across batches; instead, it requires only that a subset of the population be shared between batches. We demonstrate the superiority of our approach compared with existing methods by using both simulated and real scRNA-seq data sets. Using multiple droplet-based scRNA-seq data sets, we demonstrate that our MNN batch-effect-correction method can be scaled to large numbers of cells.

1,423 citations

Journal ArticleDOI
28 Jul 2016-Cell
TL;DR: It is reported how cancer-driven alterations identified in 11,289 tumors from 29 tissues can be mapped onto 1,001 molecularly annotated human cancer cell lines and correlated with sensitivity to 265 drugs.

1,414 citations

Journal ArticleDOI
TL;DR: The structure and content of CellPhoneDB is outlined, procedures for inferring cell–cell communication networks from single-cell RNA sequencing data are provided and a practical step-by-step guide to help implement the protocol is presented.
Abstract: Cell–cell communication mediated by ligand–receptor complexes is critical to coordinating diverse biological processes, such as development, differentiation and inflammation. To investigate how the context-dependent crosstalk of different cell types enables physiological processes to proceed, we developed CellPhoneDB, a novel repository of ligands, receptors and their interactions. In contrast to other repositories, our database takes into account the subunit architecture of both ligands and receptors, representing heteromeric complexes accurately. We integrated our resource with a statistical framework that predicts enriched cellular interactions between two cell types from single-cell transcriptomics data. Here, we outline the structure and content of our repository, provide procedures for inferring cell–cell communication networks from single-cell RNA sequencing data and present a practical step-by-step guide to help implement the protocol. CellPhoneDB v.2.0 is an updated version of our resource that incorporates additional functionalities to enable users to introduce new interacting molecules and reduces the time and resources needed to interrogate large datasets. CellPhoneDB v.2.0 is publicly available, both as code and as a user-friendly web interface; it can be used by both experts and researchers with little experience in computational genomics. In our protocol, we demonstrate how to evaluate meaningful biological interactions with CellPhoneDB v.2.0 using published datasets. This protocol typically takes ~2 h to complete, from installation to statistical analysis and visualization, for a dataset of ~10 GB, 10,000 cells and 19 cell types, and using five threads. CellPhoneDB combines an interactive database and a statistical framework for the exploration of ligand–receptor interactions inferred from single-cell transcriptomics measurements.

1,392 citations

Journal ArticleDOI
Aviv Regev1, Aviv Regev2, Aviv Regev3, Sarah A. Teichmann4, Sarah A. Teichmann5, Sarah A. Teichmann6, Eric S. Lander2, Eric S. Lander7, Eric S. Lander3, Ido Amit8, Christophe Benoist7, Ewan Birney5, Bernd Bodenmiller5, Bernd Bodenmiller9, Peter J. Campbell4, Peter J. Campbell6, Piero Carninci4, Menna R. Clatworthy10, Hans Clevers11, Bart Deplancke12, Ian Dunham5, James Eberwine13, Roland Eils14, Roland Eils15, Wolfgang Enard16, Andrew Farmer, Lars Fugger17, Berthold Göttgens4, Nir Hacohen3, Nir Hacohen7, Muzlifah Haniffa18, Martin Hemberg6, Seung K. Kim19, Paul Klenerman17, Paul Klenerman20, Arnold R. Kriegstein21, Ed S. Lein22, Sten Linnarsson23, Emma Lundberg24, Emma Lundberg19, Joakim Lundeberg24, Partha P. Majumder, John C. Marioni6, John C. Marioni4, John C. Marioni5, Miriam Merad25, Musa M. Mhlanga26, Martijn C. Nawijn27, Mihai G. Netea28, Garry P. Nolan19, Dana Pe'er29, Anthony Phillipakis3, Chris P. Ponting30, Stephen R. Quake19, Wolf Reik4, Wolf Reik31, Wolf Reik6, Orit Rozenblatt-Rosen3, Joshua R. Sanes7, Rahul Satija32, Ton N. Schumacher33, Alex K. Shalek3, Alex K. Shalek34, Alex K. Shalek2, Ehud Shapiro8, Padmanee Sharma35, Jay W. Shin, Oliver Stegle5, Michael R. Stratton6, Michael J. T. Stubbington6, Fabian J. Theis36, Matthias Uhlen37, Matthias Uhlen24, Alexander van Oudenaarden11, Allon Wagner38, Fiona M. Watt39, Jonathan S. Weissman, Barbara J. Wold40, Ramnik J. Xavier, Nir Yosef38, Nir Yosef34, Human Cell Atlas Meeting Participants 
05 Dec 2017-eLife
TL;DR: An open comprehensive reference map of the molecular state of cells in healthy human tissues would propel the systematic study of physiological states, developmental trajectories, regulatory circuitry and interactions of cells, and also provide a framework for understanding cellular dysregulation in human disease.
Abstract: The recent advent of methods for high-throughput single-cell molecular profiling has catalyzed a growing sense in the scientific community that the time is ripe to complete the 150-year-old effort to identify all cell types in the human body. The Human Cell Atlas Project is an international collaborative effort that aims to define all human cell types in terms of distinctive molecular profiles (such as gene expression profiles) and to connect this information with classical cellular descriptions (such as location and morphology). An open comprehensive reference map of the molecular state of cells in healthy human tissues would propel the systematic study of physiological states, developmental trajectories, regulatory circuitry and interactions of cells, and also provide a framework for understanding cellular dysregulation in human disease. Here we describe the idea, its potential utility, early proofs-of-concept, and some design considerations for the Human Cell Atlas, including a commitment to open data, code, and community.

1,391 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