[Gene expression profile analysis of T lymphocytes involved in pathogenesis of severe aplastic anemia by using bioinformatics method as a novel way of drug screening].
This study was aimed to explore the gene expression profile characteristics of T lymphocytes involved in pathogenesis of severe aplastic anemia (SAA) and to predict putative curative drugs for SAA by using biological principle of similarity contrast of gene expression profiles between drugs and diseases. SAA and T lymphocyte were used as key words to search gene expression datasets related to pathogenesis of SAA in public Gene Expression Omnibus (GEO) of NCBI. After significance test, gene expression profiling involved in pathogenesis of SAA were screened and applied to cluster analysis. And then SAA-related gene expression profiles were thrown into pharmacological gene expression datasets of 3000 candidate drugs for similarity analysis and significantly negative correlation was used as a screening criterion for selecting putative curative drugs of SAA. The results showed that only one gene expression dataset was found out, i.e. GSE3807. Computational bioanalysis identified a total of 515 candidate genes of T lymphocyte involved in pathogenesis of SAA, whose expression level exceeded more than 2-fold. Among them, 202 genes were upregulated and 313 genes were downregulated. Cluster analysis showed that those genes belonged to different pathways, including nucleic acid metabolic process, ubiquitin-dependent protein catabolic process, Golgi apparatus protein transport, protein phosphorylation and immunoglobin/major histocompatibility complex. Similarity analysis of gene expression profiles of SAA and drugs showed that hydroxycamptothecin and metformin might have a potential therapeutic efficacy on SAA. It is concluded that by means of novel bioinformatics method, gene expression profiling combined with similarity analysis between disease-related gene expression and pharmacological gene expression profiles may be a novel way of drug screening for SAA.
Lu
Xue-Chun
XC
Department of Geriatric Hematology, Chinese PLA General Hospital, Beijing 100853, China. luxuechun@126.com
Chi
Xiao-Hua
XH
Yang
Bo
B
Zhu
Hong-Li
HL
Liu
Li-Hong
LH
Zhang
Feng
F
Yan
Jiang-Wei
JW
D000741:Anemia, Aplastic / Q000235:genetics*; D019295:Computational Biology; D004353:Drug Evaluation, Preclinical; D020869:Gene Expression Profiling; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D013601:T-Lymphocytes / Q000378:metabolism*