title: PATHOME: an algorithm for accurately detecting differentially expressed subpathways.
abstract: The translation of high-throughput gene expression data into biologically meaningful information remains a bottleneck. We developed a novel computational algorithm, PATHOME, for detecting differentially expressed biological pathways. This algorithm employs straightforward statistical tests to evaluate the significance of differential expression patterns along subpathways. Applying it to gene expression data sets of gastric cancer (GC), we compared its performance with those of other leading programs. Based on a literature-driven reference set, PATHOME showed greater consistency in identifying known cancer-related pathways. For the WNT pathway uniquely identified by PATHOME, we validated its involvement in gastric carcinogenesis through experimental perturbation of both cell lines and animal models. We identified HNF4α-WNT5A regulation in the cross-talk between the AMPK metabolic pathway and the WNT signaling pathway, and further identified WNT5A as a potential therapeutic target for GC. We have demonstrated PATHOME to be a powerful tool, with improved sensitivity for identifying disease-related dysregulated pathways.
authors.affiliation: Cancer Genomics Branch, National Cancer Center of Korea, Goyang-si Gyeonggi-do, Republic of Korea.
authors.forename: S
authors.initials: S
authors.lastname: Nam
authors.affiliation: New Experimental Therapeutics Branch, National Cancer Center of Korea, Goyang-si Gyeonggi-do, Republic of Korea.
authors.forename: H R
authors.initials: HR
authors.lastname: Chang
authors.affiliation: Molecular Epidemiology Branch, National Cancer Center of Korea, Goyang-si Gyeonggi-do, Republic of Korea.
authors.forename: K-T
authors.initials: KT
authors.lastname: Kim
authors.affiliation: Department of Pathology, National Cancer Center of Korea, Goyang-si Gyeonggi-do, Republic of Korea.
authors.forename: M-C
authors.initials: MC
authors.lastname: Kook
authors.affiliation: Cancer Genomics Branch, National Cancer Center of Korea, Goyang-si Gyeonggi-do, Republic of Korea.
authors.forename: D
authors.initials: D
authors.lastname: Hong
authors.affiliation: Cancer Genomics Branch, National Cancer Center of Korea, Goyang-si Gyeonggi-do, Republic of Korea.
authors.forename: C H
authors.initials: CH
authors.lastname: Kwon
authors.affiliation: New Experimental Therapeutics Branch, National Cancer Center of Korea, Goyang-si Gyeonggi-do, Republic of Korea.
authors.forename: H R
authors.initials: HR
authors.lastname: Jung
authors.affiliation: New Experimental Therapeutics Branch, National Cancer Center of Korea, Goyang-si Gyeonggi-do, Republic of Korea.
authors.forename: H S
authors.initials: HS
authors.lastname: Park
authors.affiliation: Cancer Center, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA.
authors.forename: G
authors.initials: G
authors.lastname: Powis
authors.affiliation: Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: H
authors.identifier: 000000017633286X
authors.initials: H
authors.lastname: Liang
authors.affiliation: Department of Statistics, Seoul National University, Kwanak-gu Seoul, Republic of Korea.
authors.forename: T
authors.initials: T
authors.lastname: Park
authors.affiliation: New Experimental Therapeutics Branch, National Cancer Center of Korea, Goyang-si Gyeonggi-do, Republic of Korea.
authors.forename: Y H
authors.initials: YH
authors.lastname: Kim
mesh_terms: D000465:Algorithms; D000818:Animals; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D006801:Humans; D009374:Neoplasms, Experimental; D015203:Reproducibility of Results; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D059467:Transcriptome; D060449:Wnt Signaling Pathway