T lymphocyte activation gene identification by coregulated expression on DNA microarrays.
High-capacity methods for assessing gene function have become increasingly important because of the increasing number of newly identified genes emerging from large-scale genome sequencing and cDNA cloning efforts. We investigated the use of DNA microarrays to identify uncharacterized genes specifically involved in human T cell activation. Activation of human peripheral blood T lymphocytes induced significant changes in hundreds of transcripts, but most of these were not unique to T cell activation. Variation of experimental parameters and analysis techniques allowed better enrichment for gene expression changes unique to T cell activation. Best results were achieved by identification of genes that were most highly coregulated with the T-cell-specific transcript interleukin 2 (IL2) in a "compendium" of experiments involving both T cells and other cell types. Among the genes most highly coregulated with IL2 were many genes known to function during T cell activation, together with ESTs of unknown function. Four of these ESTs were extended to novel full-length clones encoding T-cell-regulated proteins with predicted functions in GTP metabolism, cell organization, and signal transduction.
Mao
Mao
M
Rosetta Inpharmatics LLC, Merck Research Laboratories, 401 Terry Avenue N, Seattle, WA 98109, USA.
Biery
Matt C
MC
Kobayashi
Sumire V
SV
Ward
Terry
T
Schimmack
Greg
G
Burchard
Julja
J
Schelter
Janell M
JM
Dai
Hongyue
H
He
Yudong D
YD
Linsley
Peter S
PS
D001483:Base Sequence; D020224:Expressed Sequence Tags; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics*; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction / Q000235:genetics; D013601:T-Lymphocytes / Q000378:metabolism*
D007376:Interleukin-2; D006160:Guanosine Triphosphate