Institution
Broad Institute
Nonprofit•Cambridge, Massachusetts, United States•
About: Broad Institute is a nonprofit organization based out in Cambridge, Massachusetts, United States. It is known for research contribution in the topics: Population & Genome-wide association study. The organization has 6584 authors who have published 11618 publications receiving 1522743 citations. The organization is also known as: Eli and Edythe L. Broad Institute of MIT and Harvard.
Papers published on a yearly basis
Papers
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TL;DR: In vitro evolution experiments found that in all cases, tolerance preceded resistance, and a mathematical population-genetics model showed how tolerance boosts the chances for resistance mutations to spread in the population.
Abstract: Controlled experimental evolution during antibiotic treatment can help to explain the processes leading to antibiotic resistance in bacteria. Recently, intermittent antibiotic exposures have been shown to lead rapidly to the evolution of tolerance—that is, the ability to survive under treatment without developing resistance. However, whether tolerance delays or promotes the eventual emergence of resistance is unclear. Here we used in vitro evolution experiments to explore this question. We found that in all cases, tolerance preceded resistance. A mathematical population-genetics model showed how tolerance boosts the chances for resistance mutations to spread in the population. Thus, tolerance mutations pave the way for the rapid subsequent evolution of resistance. Preventing the evolution of tolerance may offer a new strategy for delaying the emergence of resistance.
835 citations
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Broad Institute1, University of Oxford2, University of Bern3, Swiss Federal Institute of Aquatic Science and Technology4, Wellcome Trust Sanger Institute5, Wellcome Trust/Cancer Research UK Gurdon Institute6, University of Konstanz7, Agency for Science, Technology and Research8, Reed College9, Stanford University10, California Institute of Technology11, Benaroya Research Institute12, University of Rennes13, Georgia Institute of Technology14, University of Maryland, College Park15, University of Basel16, University of Texas at Austin17, Tokyo Institute of Technology18, National Museum of Natural History19, University of Stirling20, Carnegie Institution for Science21, National Cheng Kung University22, Science for Life Laboratory23, Norwich University24
TL;DR: This article found an excess of gene duplications in the East African lineage compared to Nile tilapia and other teleosts, an abundance of non-coding element divergence, accelerated coding sequence evolution, expression divergence associated with transposable element insertions, and regulation by novel microRNAs.
Abstract: Cichlid fishes are famous for large, diverse and replicated adaptive radiations in the Great Lakes of East Africa. To understand the molecular mechanisms underlying cichlid phenotypic diversity, we sequenced the genomes and transcriptomes of five lineages of African cichlids: the Nile tilapia (Oreochromis niloticus), an ancestral lineage with low diversity; and four members of the East African lineage: Neolamprologus brichardi/pulcher (older radiation, Lake Tanganyika), Metriaclima zebra (recent radiation, Lake Malawi), Pundamilia nyererei (very recent radiation, Lake Victoria), and Astatotilapia burtoni (riverine species around Lake Tanganyika). We found an excess of gene duplications in the East African lineage compared to tilapia and other teleosts, an abundance of non-coding element divergence, accelerated coding sequence evolution, expression divergence associated with transposable element insertions, and regulation by novel microRNAs. In addition, we analysed sequence data from sixty individuals representing six closely related species from Lake Victoria, and show genome-wide diversifying selection on coding and regulatory variants, some of which were recruited from ancient polymorphisms. We conclude that a number of molecular mechanisms shaped East African cichlid genomes, and that amassing of standing variation during periods of relaxed purifying selection may have been important in facilitating subsequent evolutionary diversification.
832 citations
01 Apr 2015
TL;DR: Seurat is a computational strategy to infer cellular localization by integrating single-cell RNA-seq data with in situ RNA patterns, and it correctly localizes rare subpopulations, accurately mapping both spatially restricted and scattered groups.
Abstract: Spatial localization is a key determinant of cellular fate and behavior, but methods for spatially resolved, transcriptome-wide gene expression profiling across complex tissues are lacking. RNA staining methods assay only a small number of transcripts, whereas single-cell RNA-seq, which measures global gene expression, separates cells from their native spatial context. Here we present Seurat, a computational strategy to infer cellular localization by integrating single-cell RNA-seq data with in situ RNA patterns. We applied Seurat to spatially map 851 single cells from dissociated zebrafish (Danio rerio) embryos and generated a transcriptome-wide map of spatial patterning. We confirmed Seurat's accuracy using several experimental approaches, then used the strategy to identify a set of archetypal expression patterns and spatial markers. Seurat correctly localizes rare subpopulations, accurately mapping both spatially restricted and scattered groups. Seurat will be applicable to mapping cellular localization within complex patterned tissues in diverse systems.
829 citations
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TL;DR: This article performed massively parallel sequencing of paired tumor/normal samples from 203 multiple myeloma (MM) patients and identified significantly mutated genes and copy number alterations and discovered putative tumor suppressor genes by determining homozygous deletions and loss of heterozygosity.
827 citations
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Massachusetts Institute of Technology1, Purdue University2, Michigan State University3, Cornell University4, University of Córdoba (Spain)5, Broad Institute6, Pacific Northwest National Laboratory7, University of Amsterdam8, University of Natural Resources and Life Sciences, Vienna9, Rothamsted Research10, University of Minnesota11, University of Ottawa12, United States Department of Agriculture13, Saint Louis University14, University of Arizona15, University of Tennessee Health Science Center16, National Center for Agricultural Utilization Research17, National Academy of Sciences of Ukraine18, Wageningen University and Research Centre19
TL;DR: The genome of the filamentous fungus Fusarium graminearum, a major pathogen of cultivated cereals, was sequenced and annotated and many highly polymorphic regions contained sets of genes implicated in plant-fungus interactions and were unusually divergent, with higher rates of recombination.
Abstract: We sequenced and annotated the genome of the filamentous fungus Fusarium graminearum, a major pathogen of cultivated cereals. Very few repetitive sequences were detected, and the process of repeat-induced point mutation, in which duplicated sequences are subject to extensive mutation, may partially account for the reduced repeat content and apparent low number of paralogous (ancestrally duplicated) genes. A second strain of F. graminearum contained more than 10,000 single-nucleotide polymorphisms, which were frequently located near telomeres and within other discrete chromosomal segments. Many highly polymorphic regions contained sets of genes implicated in plant-fungus interactions and were unusually divergent, with higher rates of recombination. These regions of genome innovation may result from selection due to interactions of F. graminearum with its plant hosts.
822 citations
Authors
Showing all 7146 results
Name | H-index | Papers | Citations |
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Eric S. Lander | 301 | 826 | 525976 |
Albert Hofman | 267 | 2530 | 321405 |
Frank B. Hu | 250 | 1675 | 253464 |
David J. Hunter | 213 | 1836 | 207050 |
Kari Stefansson | 206 | 794 | 174819 |
Mark J. Daly | 204 | 763 | 304452 |
Lewis C. Cantley | 196 | 748 | 169037 |
Matthew Meyerson | 194 | 553 | 243726 |
Gad Getz | 189 | 520 | 247560 |
Stacey Gabriel | 187 | 383 | 294284 |
Stuart H. Orkin | 186 | 715 | 112182 |
Ralph Weissleder | 184 | 1160 | 142508 |
Chris Sander | 178 | 713 | 233287 |
Michael I. Jordan | 176 | 1016 | 216204 |
Richard A. Young | 173 | 520 | 126642 |