A modular analysis framework for blood genomics studies: application to systemic lupus erythematosus.
The analysis of patient blood transcriptional profiles offers a means to investigate the immunological mechanisms relevant to human diseases on a genome-wide scale. In addition, such studies provide a basis for the discovery of clinically relevant biomarker signatures. We designed a strategy for microarray analysis that is based on the identification of transcriptional modules formed by genes coordinately expressed in multiple disease data sets. Mapping changes in gene expression at the module level generated disease-specific transcriptional fingerprints that provide a stable framework for the visualization and functional interpretation of microarray data. These transcriptional modules were used as a basis for the selection of biomarkers and the development of a multivariate transcriptional indicator of disease progression in patients with systemic lupus erythematosus. Thus, this work describes the implementation and application of a methodology designed to support systems-scale analysis of the human immune system in translational research settings.
Chaussabel
Damien
D
Baylor NIAID Cooperative Center for Translational Research on Human Immunology and Biodefense, Baylor Institute for Immunology Research and Baylor Research Institute, Dallas, TX 75204, USA. damienc@baylorhealth.edu
Quinn
Charles
C
Shen
Jing
J
Patel
Pinakeen
P
Glaser
Casey
C
Baldwin
Nicole
N
Stichweh
Dorothee
D
Blankenship
Derek
D
Li
Lei
L
Munagala
Indira
I
Bennett
Lynda
L
Allantaz
Florence
F
Mejias
Asuncion
A
Ardura
Monica
M
Kaizer
Ellen
E
Monnet
Laurence
L
Allman
Windy
W
Randall
Henry
H
Johnson
Diane
D
Lanier
Aimee
A
Punaro
Marilynn
M
Wittkowski
Knut M
KM
White
Perrin
P
Fay
Joseph
J
Klintmalm
Goran
G
Ramilo
Octavio
O
Palucka
A Karolina
AK
Banchereau
Jacques
J
Pascual
Virginia
V
D000293:Adolescent; D002648:Child; D019295:Computational Biology / Q000379:methods; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D023281:Genomics / Q000379:methods*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000235:genetics*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*