Unsupervised analysis of transcriptomics in bacterial sepsis across multiple datasets reveals three robust clusters
Timothy E. Sweeney,Tej D. Azad,Michele Donato,Winston A. Haynes,Thanneer M. Perumal,Ricardo Henao,Jesus F. Bermejo-Martin,Raquel Almansa,Eduardo Tamayo,Judith A. Howrylak,Augustine M.K. Choi,Grant P Parnell,Benjamin Tang,Marshall Nichols,Christopher W. Woods,Christopher W. Woods,Geoffrey S. Ginsburg,Stephen F. Kingsmore,Larsson Omberg,Lara M. Mangravite,Hector R. Wong,Ephraim L. Tsalik,Ephraim L. Tsalik,Raymond J. Langley,Purvesh Khatri +24 more
TLDR
A unified clustering analysis across 14 discovery datasets revealed three sepsis subtypes, which, based on functional analysis, were termed “Inflammopathic, Adaptive, and Coagulopathic,” which may represent a unifying framework for understanding the molecular heterogeneity of the sepsi syndrome.Abstract:
Objectives:To find and validate generalizable sepsis subtypes using data-driven clustering.Design:We used advanced informatics techniques to pool data from 14 bacterial sepsis transcriptomic datasets from eight different countries (n = 700).Setting:Retrospective analysis.Subjects:Persons admitted toread more
Citations
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Journal ArticleDOI
Derivation, Validation, and Potential Treatment Implications of Novel Clinical Phenotypes for Sepsis.
Christopher W. Seymour,Jason Kennedy,Shu Wang,Chung-Chou H. Chang,Corrine F. Elliott,Zhongying Xu,Scott M. Berry,Gilles Clermont,Gregory F. Cooper,Hernando Gomez,David T. Huang,John A. Kellum,Qi Mi,Steven M. Opal,Victor B. Talisa,Tom van der Poll,Shyam Visweswaran,Yoram Vodovotz,Jeremy C. Weiss,Donald M. Yealy,Sachin Yende,Sachin Yende,Derek C. Angus +22 more
TL;DR: In this retrospective analysis of data sets from patients with sepsis, 4 clinical phenotypes were identified that correlated with host-response patterns and clinical outcomes, and simulations suggested these phenotypes may help in understanding heterogeneity of treatment effects.
Journal ArticleDOI
An immune-cell signature of bacterial sepsis
Miguel Reyes,Miguel Reyes,Michael R. Filbin,Michael R. Filbin,Roby P. Bhattacharyya,Roby P. Bhattacharyya,Kianna Billman,Thomas Eisenhaure,Deborah T. Hung,Deborah T. Hung,Bruce D. Levy,Rebecca M. Baron,Paul C. Blainey,Paul C. Blainey,Marcia B. Goldberg,Marcia B. Goldberg,Nir Hacohen,Nir Hacohen +17 more
TL;DR: The utility of single-cell genomics in discovering disease-associated cytologic signatures is demonstrated and insight into the cellular basis of immune dysregulation in bacterial sepsis is provided.
Journal ArticleDOI
Latent class analysis of ARDS subphenotypes: a secondary analysis of the statins for acutely injured lungs from sepsis (SAILS) study
Pratik Sinha,Kevin L. Delucchi,B. Taylor Thompson,Daniel F. McAuley,Daniel F. McAuley,Michael A. Matthay,Carolyn S. Calfee +6 more
TL;DR: LCA using a two-subphenotype model best described the SAILS population and validated the presence of two subphenotypes and demonstrate their utility for patient stratification in ARDS.
Journal ArticleDOI
Current gaps in sepsis immunology: new opportunities for translational research.
Ignacio Rubio,Marcin F. Osuchowski,Manu Shankar-Hari,Manu Shankar-Hari,Tomasz Skirecki,Martin Sebastian Winkler,Gunnar Lachmann,Paul La Rosée,Guillaume Monneret,Fabienne Venet,Michael Bauer,Frank M. Brunkhorst,Matthijs Kox,Jean-Marc Cavaillon,Florian Uhle,Markus A. Weigand,Stefanie B. Flohé,W. Joost Wiersinga,Marta Martín-Fernández,Raquel Almansa,Raquel Almansa,Ignacio Martin-Loeches,Antoni Torres,Antoni Torres,Evangelos J. Giamarellos-Bourboulis,Massimo Girardis,Andrea Cossarizza,Mihai G. Netea,Mihai G. Netea,Mihai G. Netea,Tom van der Poll,André Scherag,Christian Meisel,Joerg C. Schefold,Jesus F. Bermejo-Martin,Jesus F. Bermejo-Martin +35 more
TL;DR: The role of key immune cells, the cause of lymphopenia, organ-specific immunology, the dynamics of sepsis-associated immunological alterations, the role of the microbiome, the standardisation of immunological tests, the development of better animal models, and the opportunities offered by immunotherapy are discussed.
Journal ArticleDOI
Biomarkers for Acute Respiratory Distress syndrome and prospects for personalised medicine
Savino Spadaro,Mirae Park,Cecilia Turrini,Tanushree Tunstall,Ryan S Thwaites,Tommaso Mauri,Riccardo Ragazzi,Paolo Ruggeri,Trevor T. Hansel,Gaetano Caramori,Carlo Alberto Volta +10 more
TL;DR: By understanding the role of biomarkers in the pathophysiology of ARDS and lung injury, it is hoped that this will provide rational therapeutic targets and ultimately improve clinical care.
References
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Journal ArticleDOI
The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)
Mervyn Singer,Clifford S. Deutschman,Christopher W. Seymour,Manu Shankar-Hari,Djillali Annane,Michael Bauer,Rinaldo Bellomo,Gordon R. Bernard,Jean-Daniel Chiche,Craig M. Coopersmith,Richard S. Hotchkiss,Mitchell M. Levy,John C. Marshall,Greg S. Martin,Steven M. Opal,Gordon D. Rubenfeld,Gordon D. Rubenfeld,Tom van der Poll,Jean Louis Vincent,Derek C. Angus +19 more
TL;DR: The task force concluded the term severe sepsis was redundant and updated definitions and clinical criteria should replace previous definitions, offer greater consistency for epidemiologic studies and clinical trials, and facilitate earlier recognition and more timely management of patients with sepsi or at risk of developing sepsic shock.
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Molecular classification of cancer: class discovery and class prediction by gene expression monitoring.
Todd R. Golub,Todd R. Golub,Donna K. Slonim,Pablo Tamayo,Christine Huard,Michelle Gaasenbeek,Jill P. Mesirov,Hilary A. Coller,Mignon L. Loh,James R. Downing,Michael A. Caligiuri,Clara D. Bloomfield,Eric S. Lander +12 more
TL;DR: A generic approach to cancer classification based on gene expression monitoring by DNA microarrays is described and applied to human acute leukemias as a test case and suggests a general strategy for discovering and predicting cancer classes for other types of cancer, independent of previous biological knowledge.
Journal ArticleDOI
Significance analysis of microarrays applied to the ionizing radiation response
TL;DR: A method that assigns a score to each gene on the basis of change in gene expression relative to the standard deviation of repeated measurements is described, suggesting that this repair pathway for UV-damaged DNA might play a previously unrecognized role in repairing DNA damaged by ionizing radiation.
Journal ArticleDOI
Gene expression profiling predicts clinical outcome of breast cancer
Laura J. van't Veer,Hongyue Dai,Marc J. van de Vijver,Yudong D. He,Augustinus A. M. Hart,Mao Mao,Hans Peterse,Karin van der Kooy,Matthew J. Marton,Anke T. Witteveen,George J. Schreiber,Ron M. Kerkhoven,Christopher J. Roberts,Peter S. Linsley,René Bernards,Stephen H. Friend +15 more
TL;DR: DNA microarray analysis on primary breast tumours of 117 young patients is used and supervised classification is applied to identify a gene expression signature strongly predictive of a short interval to distant metastases (‘poor prognosis’ signature) in patients without tumour cells in local lymph nodes at diagnosis, providing a strategy to select patients who would benefit from adjuvant therapy.
Journal ArticleDOI
Efficacy and safety of recombinant human activated protein C for severe sepsis.
G Ordon R. B Ernard,J Ean L Ouis V Incent,L Aterre,S Teven P. L A R Osa,J Ean,A Ngel L Opez,J Ay S. S Teingrub,G Ary E. G Arber,J Effrey,D. H Elterbrand,E. W Esley E Ly,C Harles J. F Isher,S Evere S Epsis,S Tudy G Roup +13 more
TL;DR: This phase 3 trial assessed whether treatment with drotrecogin alfa activated reduced the rate of death from any cause among patients with severe sepsis.
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