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Institution

Institute for Systems Biology

Nonprofit•Seattle, Washington, United States•
About: Institute for Systems Biology is a nonprofit organization based out in Seattle, Washington, United States. It is known for research contribution in the topics: Population & Proteomics. The organization has 1277 authors who have published 2777 publications receiving 353165 citations.
Topics: Population, Proteomics, Proteome, Systems biology, Gene


Papers
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Journal Article•DOI•
26 Apr 2001-Nature
TL;DR: It is reported that mammalian TLR5 recognizes bacterial flagellin from both Gram-positive and Gram-negative bacteria, and that activation of the receptor mobilizes the nuclear factor NF-κB and stimulates tumour necrosis factor-α production, and the data suggest thatTLR5, a member of the evolutionarily conserved Toll-like receptor family, has evolved to permit mammals specifically to detect flageLLated bacterial pathogens.
Abstract: The innate immune system recognizes pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents, but not on the host. Toll-like receptors (TLRs) recognize PAMPs and mediate the production of cytokines necessary for the development of effective immunity. Flagellin, a principal component of bacterial flagella, is a virulence factor that is recognized by the innate immune system in organisms as diverse as flies, plants and mammals. Here we report that mammalian TLR5 recognizes bacterial flagellin from both Gram-positive and Gram-negative bacteria, and that activation of the receptor mobilizes the nuclear factor NF-kappaB and stimulates tumour necrosis factor-alpha production. TLR5-stimulating activity was purified from Listeria monocytogenes culture supernatants and identified as flagellin by tandem mass spectrometry. Expression of L. monocytogenes flagellin in non-flagellated Escherichia coli conferred on the bacterium the ability to activate TLR5, whereas deletion of the flagellin genes from Salmonella typhimurium abrogated TLR5-stimulating activity. All known TLRs signal through the adaptor protein MyD88. Mice challenged with bacterial flagellin rapidly produced systemic interleukin-6, whereas MyD88-null mice did not respond to flagellin. Our data suggest that TLR5, a member of the evolutionarily conserved Toll-like receptor family, has evolved to permit mammals specifically to detect flagellated bacterial pathogens.

3,575 citations

Journal Article•DOI•
17 Apr 2018-Immunity
TL;DR: An extensive immunogenomic analysis of more than 10,000 tumors comprising 33 diverse cancer types by utilizing data compiled by TCGA identifies six immune subtypes that encompass multiple cancer types and are hypothesized to define immune response patterns impacting prognosis.

3,246 citations

Journal Article•DOI•
LaDeana W. Hillier1, Webb Miller2, Ewan Birney, Wesley C. Warren1  +171 more•Institutions (39)
09 Dec 2004-Nature
TL;DR: A draft genome sequence of the red jungle fowl, Gallus gallus, provides a new perspective on vertebrate genome evolution, while also improving the annotation of mammalian genomes.
Abstract: We present here a draft genome sequence of the red jungle fowl, Gallus gallus. Because the chicken is a modern descendant of the dinosaurs and the first non-mammalian amniote to have its genome sequenced, the draft sequence of its genome--composed of approximately one billion base pairs of sequence and an estimated 20,000-23,000 genes--provides a new perspective on vertebrate genome evolution, while also improving the annotation of mammalian genomes. For example, the evolutionary distance between chicken and human provides high specificity in detecting functional elements, both non-coding and coding. Notably, many conserved non-coding sequences are far from genes and cannot be assigned to defined functional classes. In coding regions the evolutionary dynamics of protein domains and orthologous groups illustrate processes that distinguish the lineages leading to birds and mammals. The distinctive properties of avian microchromosomes, together with the inferred patterns of conserved synteny, provide additional insights into vertebrate chromosome architecture.

2,579 citations

Journal Article•DOI•
Chad J. Creighton1, Margaret Morgan1, Preethi H. Gunaratne2, Preethi H. Gunaratne1  +288 more•Institutions (27)
28 Aug 2013-Nature
TL;DR: Remodelling cellular metabolism constitutes a recurrent pattern in ccRCC that correlates with tumour stage and severity and offers new views on the opportunities for disease treatment.
Abstract: Genetic changes underlying clear cell renal cell carcinoma (ccRCC) include alterations in genes controlling cellular oxygen sensing (for example, VHL) and the maintenance of chromatin states (for example, PBRM1). We surveyed more than 400 tumours using different genomic platforms and identified 19 significantly mutated genes. The PI(3)K/AKT pathway was recurrently mutated, suggesting this pathway as a potential therapeutic target. Widespread DNA hypomethylation was associated with mutation of the H3K36 methyltransferase SETD2, and integrative analysis suggested that mutations involving the SWI/SNF chromatin remodelling complex (PBRM1, ARID1A, SMARCA4) could have far-reaching effects on other pathways. Aggressive cancers demonstrated evidence of a metabolic shift, involving downregulation of genes involved in the TCA cycle, decreased AMPK and PTEN protein levels, upregulation of the pentose phosphate pathway and the glutamine transporter genes, increased acetyl-CoA carboxylase protein, and altered promoter methylation of miR-21 (also known as MIR21) and GRB10. Remodelling cellular metabolism thus constitutes a recurrent pattern in ccRCC that correlates with tumour stage and severity and offers new views on the opportunities for disease treatment.

2,548 citations

Journal Article•DOI•
TL;DR: The ProteoWizard Toolkit is developed, a robust set of open-source, software libraries and applications designed to facilitate proteomics research that implements the first-ever, non-commercial, unified data access interface for proteomics, bridging field-standard open formats and all common vendor formats.
Abstract: Mass-spectrometry-based proteomics has become an important component of biological research. Numerous proteomics methods have been developed to identify and quantify the proteins in biological and clinical samples1, identify pathways affected by endogenous and exogenous perturbations2, and characterize protein complexes3. Despite successes, the interpretation of vast proteomics datasets remains a challenge. There have been several calls for improvements and standardization of proteomics data analysis frameworks, as well as for an application-programming interface for proteomics data access4,5. In response, we have developed the ProteoWizard Toolkit, a robust set of open-source, software libraries and applications designed to facilitate proteomics research. The libraries implement the first-ever, non-commercial, unified data access interface for proteomics, bridging field-standard open formats and all common vendor formats. In addition, diverse software classes enable rapid development of vendor-agnostic proteomics software. Additionally, ProteoWizard projects and applications, building upon the core libraries, are becoming standard tools for enabling significant proteomics inquiries.

2,480 citations


Authors

Showing all 1292 results

NameH-indexPapersCitations
Younan Xia216943175757
Ruedi Aebersold182879141881
David Haussler172488224960
Steven P. Gygi172704129173
Nahum Sonenberg167647104053
Leroy Hood158853128452
Mark H. Ellisman11763755289
Wei Zhang112118993641
John Ralph10944239238
Eric H. Davidson10645447058
James R. Heath10342558548
Alan Aderem9924646682
Anne-Claude Gingras9733640714
Trey Ideker9730672276
Michael H. Gelb9450634714
Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
20233
202260
2021216
2020204
2019188
2018168