[Recent progress in bioinformatics for microarray analysis].
Following the completion of the Human Genome Project in 2003, we were able to clarify the comprehensive profile of the whole human genome on DNA microarray. KeyMolnet is a bioinformatics tool for analyzing molecular interactions on the curated knowledge database. It promotes genome-based drug discovery research aimed at mining the most relevant molecular target to personalized medicine. Multiple sclerosis (MS) is an inflammatory demyelinating disease with a relapsing-remitting clinical course, affecting exclusively the human central nervous system white matter. By DNA microarray, we identified a set of differentially expressed genes in T lymphocytes between MS and healthy subjects, and between acute relapse and complete remission. Hierarchical clustering of discriminator genes established the molecular classification of MS subgroups, associated with the therapeutic response to interferon-beta. The molecular network of the genes involved in development of MS and induction of acute relapse of MS was related to NF-kappaB-regulated gene expression. Prion diseases are an intractable neurodegenerative disease, mediated by an abnormal prion protein PrPSc. The protein conformational conversion from the cellular prion protein PrPC to PrPSc requires an as yet unidentified species-specific chaperone named "Protein X". By protein microarray, we identified a set of novel PrPC interactors, serving as the candidate for X. The molecular network of PrPC and interactors was closely associated with signaling pathways essential for cell survival, differentiation, proliferation and apoptosis. Thus, the molecular network analysis is highly valuable to extract biological implications from a huge amount of microarray data.
Satoh
Jun-ichi
J
Department of Bioinformatics, Faculty of Pharmaceutical Sciences, Meiji Pharmaceutical University, Kiyose City, Tokyo, Japan. satoj@my-pharm.ac.jp
D000818:Animals; D019295:Computational Biology / Q000379:methods / Q000639:trends*; D030541:Databases, Genetic; D055808:Drug Discovery; D005786:Gene Expression Regulation; D006801:Humans; D016899:Interferon-beta; D046228:Microarray Analysis; D009103:Multiple Sclerosis / Q000145:classification / Q000235:genetics / Q000628:therapy; D016328:NF-kappa B / Q000235:genetics; D010597:Pharmacogenetics; D018621:PrPC Proteins / Q000235:genetics; D017096:Prion Diseases / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
D016328:NF-kappa B; D018621:PrPC Proteins; D016899:Interferon-beta