title: The reverse-direction method links mass experimental data to human diseases.
abstract: Genome-wide analyses such as DNA microarray, RNA sequencing and RNA interference-based high-throughput screening are prevalent to decipher a biological process of interest, and provide a large quantity of data to be processed. An ultimate goal for researchers must be extrapolation of their data to human diseases. We have conducted functional genome-wide screenings to elucidate molecular mechanisms of the inflammation amplifier, a NFκB/STAT3-dependent machinery that potently drives recruitment of immune cells to promote inflammation. Using a public database of genome-wide association studies (GWAS), we recently reported the reverse-direction method by which our mass screening data were successfully linked to many human diseases. As an example, the epiregulin-epidermal growth factor receptor pathway was identified as a regulator of the inflammation amplifier, and associated with human diseases by GWAS. In fact, serum epiregulin levels were higher in patients with chronic inflammatory disorders. The reverse-direction method can be a useful tool to narrow mass data down to focus on human disease-related genes.
authors.affiliation: Laboratory of Developmental Immunology JST-CREST, Graduate School of Frontier Biosciences, Graduate School of Medicine, and WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Ogura
authors.forename: Toru
authors.initials: T
authors.lastname: Atsumi
authors.forename: Hidenori
authors.initials: H
authors.lastname: Bando
authors.forename: Lavannya
authors.initials: L
authors.lastname: Sabharwal
authors.forename: Moe
authors.initials: M
authors.lastname: Yamada
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Jiang
authors.forename: Akihiro
authors.initials: A
authors.lastname: Nakamura
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Arima
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kamimura
authors.forename: Masaaki
authors.initials: M
authors.lastname: Murakami
mesh_terms: D000818:Animals; D002465:Cell Movement; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism; D066260:Epiregulin; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D055106:Genome-Wide Association Study; D057166:High-Throughput Screening Assays; D006801:Humans; D007154:Immune System Diseases / Q000175:diagnosis* / Q000276:immunology*; D018836:Inflammation Mediators / Q000378:metabolism; D008403:Mass Screening / Q000379:methods* / Q000639:trends; D016328:NF-kappa B / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D057170:Translational Research, Biomedical
chemical_list: C587880:EREG protein, human; D066260:Epiregulin; D018836:Inflammation Mediators; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; D004815:Epidermal Growth Factor; C512478:EGFR protein, human; D066246:ErbB Receptors