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.
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01 Apr 2012TL;DR: This unit outlines procedures for extracting nitrogenous metabolites, lipids, and intermediary metabolites (including TCA cycle oxoacids) from blood plasma using targeted metabolomics experiments based on liquid chromatography−mass spectrometry.
Abstract: The metabolome is the terminal downstream product of the genome and consists of the total complement of all the low-molecular-weight molecules (metabolites) in a cell, tissue, or organism. Metabolomics aims to measure a wide breadth of small molecules in the context of physiological stimuli or disease states. Metabolomics methodologies fall into two distinct groups: untargeted metabolomics, an intended comprehensive analysis of all the measurable analytes in a sample including chemical unknowns, and targeted metabolomics, the measurement of defined groups of chemically characterized and biochemically annotated metabolites. The methodologies considered in this unit focus on the processes of conducting targeted metabolomics experiments, and the advantages of this general approach are highlighted herein. This unit outlines procedures for extracting nitrogenous metabolites (including amino acids), lipids, and intermediary metabolites (including TCA cycle oxoacids) from blood plasma. Specifically, protocols are described for analyzing these metabolites using targeted metabolomics experiments based on liquid chromatography−mass spectrometry. Curr. Protoc. Mol. Biol. 98:30.2.1-30.2.24. © 2012 by John Wiley & Sons, Inc.
Keywords:
targeted metabolomics;
liquid chromatography−mass spectrometry;
multiple reaction monitoring
431 citations
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Emory University1, Cincinnati Children's Hospital Medical Center2, University of Toronto3, Georgia Institute of Technology4, Broad Institute5, Harvard University6, Medical College of Wisconsin7, Ohio State University8, Boston Children's Hospital9, Cedars-Sinai Medical Center10, University of Utah11, Children's Hospital of Eastern Ontario12, Baylor College of Medicine13, University of North Carolina at Chapel Hill14, Indiana University15, Vanderbilt University16, Johns Hopkins University School of Medicine17, University of California, San Francisco18, Dalhousie University19, University at Buffalo20, Nemours Foundation21, University of Chicago22, University of Texas Southwestern Medical Center23, University of California, Los Angeles24, Mayo Clinic25, University of Pennsylvania26, Mount Sinai Hospital27, Massachusetts Institute of Technology28
TL;DR: The findings support the usefulness of risk stratification of paediatric patients with Crohn's disease at diagnosis, and selection of anti-TNFα therapy.
431 citations
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TL;DR: It is demonstrated that TIGIT can inhibit T cell responses directly independent of APCs by generating an agonistic anti-TIGIT Ab, and can act directly on T cells by attenuating TCR-driven activation signals.
Abstract: Costimulatory molecules regulate the functional outcome of T cell activation, and disturbance of the balance between activating and inhibitory signals results in increased susceptibility to infection or the induction of autoimmunity. Similar to the well-characterized CD28/CTLA-4 costimulatory pathway, a newly emerging pathway consisting of CD226 and T cell Ig and ITIM domain (TIGIT) has been associated with susceptibility to multiple autoimmune diseases. In this study, we examined the role of the putative coinhibitory molecule TIGIT and show that loss of TIGIT in mice results in hyperproliferative T cell responses and increased susceptibility to autoimmunity. TIGIT is thought to indirectly inhibit T cell responses by the induction of tolerogenic dendritic cells. By generating an agonistic anti-TIGIT Ab, we demonstrate that TIGIT can inhibit T cell responses directly independent of APCs. Microarray analysis of T cells stimulated with agonistic anti-TIGIT Ab revealed that TIGIT can act directly on T cells by attenuating TCR-driven activation signals.
431 citations
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TL;DR: The accumulation of somatic mutations with age shows age-related, region- related, and disease-related molecular signatures and may be important in other human age-associated conditions.
Abstract: It has long been hypothesized that aging and neurodegeneration are associated with somatic mutation in neurons; however, methodological hurdles have prevented testing this hypothesis directly. We used single-cell whole-genome sequencing to perform genome-wide somatic single-nucleotide variant (sSNV) identification on DNA from 161 single neurons from the prefrontal cortex and hippocampus of fifteen normal individuals (aged 4 months to 82 years) as well as nine individuals affected by early-onset neurodegeneration due to genetic disorders of DNA repair (Cockayne syndrome and Xeroderma pigmentosum). sSNVs increased approximately linearly with age in both areas (with a higher rate in hippocampus) and were more abundant in neurodegenerative disease. The accumulation of somatic mutations with age—which we term genosenium—shows age-related, region-related, and disease-related molecular signatures, and may be important in other human age-associated conditions.
430 citations
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Broad Institute1, Brigham and Women's Hospital2, University of Michigan3, The Feinstein Institute for Medical Research4, University of North Carolina at Chapel Hill5, University of California, San Francisco6, Medical University of South Carolina7, Texas Tech University Health Sciences Center at El Paso8, New York University9, Johns Hopkins University10, Albert Einstein College of Medicine11, University of California, San Diego12, University of Cincinnati Academic Health Center13, University of Cincinnati14, Cincinnati Children's Hospital Medical Center15, University of Rochester Medical Center16
TL;DR: Analysis of kidney samples from patients with lupus nephritis and healthy control subjects revealed 21 subsets of leukocytes active in disease, including multiple populations of myeloid cells, T cells, natural killer cells and B cells that demonstrated both pro-inflammatory responses and inflammation-resolving responses.
Abstract: Lupus nephritis is a potentially fatal autoimmune disease for which the current treatment is ineffective and often toxic. To develop mechanistic hypotheses of disease, we analyzed kidney samples from patients with lupus nephritis and from healthy control subjects using single-cell RNA sequencing. Our analysis revealed 21 subsets of leukocytes active in disease, including multiple populations of myeloid cells, T cells, natural killer cells and B cells that demonstrated both pro-inflammatory responses and inflammation-resolving responses. We found evidence of local activation of B cells correlated with an age-associated B-cell signature and evidence of progressive stages of monocyte differentiation within the kidney. A clear interferon response was observed in most cells. Two chemokine receptors, CXCR4 and CX3CR1, were broadly expressed, implying a potentially central role in cell trafficking. Gene expression of immune cells in urine and kidney was highly correlated, which would suggest that urine might serve as a surrogate for kidney biopsies.
430 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 |