Data-Driven Asthma Endotypes Defined from Blood Biomarker and Gene Expression Data

被引：21

作者：

George, Barbara Jane ^{[1
]}

Reif, David M. ^{[2
]}

Gallagher, Jane E. ^{[3
]}

Williams-DeVane, ClarLynda R. ^{[4
]}

Heidenfelder, Brooke L. ^{[3
]}

Hudgens, Edward E. ^{[3
]}

Jones, Wendell ^{[5
]}

Neas, Lucas ^{[3
]}

Hubal, Elaine A. Cohen ^{[6
]}

Edwards, Stephen W. ^{[4
]}

机构：

[1] US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA

[2] US EPA, Natl Ctr Computat Toxicol, Res Triangle Pk, NC 27711 USA

[3] US EPA, Natl Hlth & Environm Effects Res Lab, Environm Publ Hlth Div, Res Triangle Pk, NC 27711 USA

[4] US EPA, Natl Hlth & Environm Effects Res Lab, Integrated Syst Toxicol Div, Res Triangle Pk, NC 27711 USA

[5] Quintiles Co, Dept Bioinformat, Express Anal, Durham, NC USA

[6] US EPA, Off Res & Dev, Res Triangle Pk, NC 27711 USA

来源：

PLOS ONE | 2015年 / 10卷 / 02期

关键词：

EXHALED NITRIC-OXIDE; OBESE INDIVIDUALS; PHENOTYPES; ASSOCIATION; IDENTIFICATION; ADIPONECTIN; CHILDREN; DISEASE;

D O I：

10.1371/journal.pone.0117445

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：19

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