title: Data-driven asthma endotypes defined from blood biomarker and gene expression data.
abstract: The diagnosis and treatment of childhood asthma is complicated by its mechanistically distinct subtypes (endotypes) driven by genetic susceptibility and modulating environmental factors. Clinical biomarkers and blood gene expression were collected from a stratified, cross-sectional study of asthmatic and non-asthmatic children from Detroit, MI. This study describes four distinct asthma endotypes identified via a purely data-driven method. Our method was specifically designed to integrate blood gene expression and clinical biomarkers in a way that provides new mechanistic insights regarding the different asthma endotypes. For example, we describe metabolic syndrome-induced systemic inflammation as an associated factor in three of the four asthma endotypes. Context provided by the clinical biomarker data was essential in interpreting gene expression patterns and identifying putative endotypes, which emphasizes the importance of integrated approaches when studying complex disease etiologies. These synthesized patterns of gene expression and clinical markers from our research may lead to development of novel serum-based biomarker panels.
authors: National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, United States of America.
authors: Barbara Jane
authors: BJ
authors: George
authors: National Center for Computational Toxicology, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, United States of America.
authors: David M
authors: DM
authors: Reif
authors: National Health and Environmental Effects Research Laboratory-Environmental Public Health Division, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, United States of America.
authors: Jane E
authors: JE
authors: Gallagher
authors: National Health and Environmental Effects Research Laboratory-Integrated Systems Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, United States of America.
authors: ClarLynda R
authors: CR
authors: Williams-DeVane
authors: National Health and Environmental Effects Research Laboratory-Environmental Public Health Division, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, United States of America.
authors: Brooke L
authors: BL
authors: Heidenfelder
authors: National Health and Environmental Effects Research Laboratory-Environmental Public Health Division, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, United States of America.
authors: Edward E
authors: EE
authors: Hudgens
authors: Department of Bioinformatics, Expression Analysis, a Quintiles company, Durham, North Carolina, United States of America.
authors: Wendell
authors: W
authors: Jones
authors: National Health and Environmental Effects Research Laboratory-Environmental Public Health Division, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, United States of America.
authors: Lucas
authors: L
authors: Neas
authors: Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, United States of America.
authors: Elaine A Cohen
authors: EA
authors: Hubal
authors: National Health and Environmental Effects Research Laboratory-Integrated Systems Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, United States of America.
authors: Stephen W
authors: SW
authors: Edwards
mesh_terms: D056704:Adaptive Immunity; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use; D001249:Asthma / Q000097:blood* / Q000145:classification* / Q000235:genetics / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D003663:Decision Trees; D004802:Eosinophilia / Q000150:complications; D006801:Humans; D007113:Immunity, Innate; D008490:Medical Informatics / Q000379:methods*; D024821:Metabolic Syndrome / Q000150:complications; D059467:Transcriptome
chemical_list: D018927:Anti-Asthmatic Agents; D015415:Biomarkers
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