Integration of multi-omics data and deep phenotyping enables prediction of cytokine responses

被引：89

作者：

Bakker, Olivier B. ^{[1
]}

Aguirre-Gamboa, Raul ^{[1
]}

Sanna, Serena ^{[1
]}

Oosting, Marije ^{[2
,3
]}

Smeekens, Sanne P. ^{[2
,3
]}

Jaeger, Martin ^{[2
,3
]}

Zorro, Maria ^{[1
]}

Vosa, Urmo ^{[1
]}

Withoff, Sebo ^{[1
]}

Netea-Maier, Romana T. ^{[4
]}

Koenen, Hans J. P. M. ^{[5
]}

Joosten, Irma ^{[5
]}

Xavier, Ramnik J. ^{[6
,7
]}

Franke, Lude ^{[1
]}

Joosten, Leo A. B. ^{[2
,3
]}

Kumar, Vinod ^{[1
,2
,3
]}

Wijmenga, Cisca ^{[1
,8
]}

Netea, Mihai G. ^{[2
,3
,9
]}

Li, Yang ^{[1
]}

机构：

[1] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands

[2] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, Nijmegen, Netherlands

[3] Radboud Univ Nijmegen, Radboud Ctr Infect Dis, Med Ctr, Nijmegen, Netherlands

[4] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, Div Endocrinol, Nijmegen, Netherlands

[5] Radboud Univ Nijmegen, Med Ctr, Dept Lab Med, Lab Med Immunol, Nijmegen, Netherlands

[6] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA

[7] Broad Inst MIT & Harvard Univ, Cambridge, MA USA

[8] Univ Oslo, Oslo Univ Hosp, Rikshosp, Dept Immunol, Oslo, Norway

[9] Univ Bonn, Life & Med Sci Inst LIMES, Dept Genom & Immunoregulat, Bonn, Germany

来源：

NATURE IMMUNOLOGY | 2018年 / 19卷 / 07期

基金：

美国国家卫生研究院; 欧洲研究理事会;

关键词：

GENOME-WIDE ASSOCIATION; RECENT POSITIVE SELECTION; CHAIN FATTY-ACIDS; SUSCEPTIBILITY LOCI; GENETIC RISK; DISEASE; LEPTIN; INFLAMMATION; TESTOSTERONE; GLUTAMINE;

D O I：

10.1038/s41590-018-0121-3

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The immune response to pathogens varies substantially among people. Whereas both genetic and nongenetic factors contribute to interperson variation, their relative contributions and potential predictive power have remained largely unknown. By systematically correlating host factors in 534 healthy volunteers, including baseline immunological parameters and molecular profiles (genome, metabolome and gut microbiome), with cytokine production after stimulation with 20 pathogens, we identified distinct patterns of co-regulation. Among the 91 different cytokine-stimulus pairs, 11 categories of host factors together explained up to 67% of interindividual variation in cytokine production induced by stimulation. A computational model based on genetic data predicted the genetic component of stimulus-induced cytokine production (correlation 0.28-0.89), and nongenetic factors influenced cytokine production as well.

引用

页码：776 / +

页数：13

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