title: Pathway bridge based multiobjective optimization approach for lurking pathway prediction.
abstract: Ovarian carcinoma immunoreactive antigen-like protein 2 (OCIAD2) is a protein with unknown function. Frequently methylated or downregulated, OCIAD2 has been observed in kinds of tumors, and TGFβ signaling has been proved to induce the expression of OCIAD2. However, current pathway analysis tools do not cover the genes without reported interactions like OCIAD2 and also miss some significant genes with relatively lower expression. To investigate potential biological milieu of OCIAD2, especially in cancer microenvironment, a nova approach pbMOO was created to find the potential pathways from TGFβ to OCIAD2 by searching on the pathway bridge, which consisted of cancer enriched looping patterns from the complicated entire protein interactions network. The pbMOO approach was further applied to study the modulator of ligand TGFβ1, receptor TGFβR1, intermediate transfer proteins, transcription factor, and signature OCIAD2. Verified by literature and public database, the pathway TGFβ1-TGFβR1-SMAD2/3-SMAD4/AR-OCIAD2 was detected, which concealed the androgen receptor (AR) which was the possible transcription factor of OCIAD2 in TGFβsignal, and it well explained the mechanism of TGFβ induced OCIAD2 expression in cancer microenvironment, therefore providing an important clue for the future functional analysis of OCIAD2 in tumor pathogenesis.
authors.affiliation: Electrical and Computer Engineering Department, Texas A&M University, College Station, TX 77840, USA.
authors.forename: Rengjing
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Radiology Comprehensive Cancer Center Cancer Biology, Wake Forest University, Winston-Salem, NC 27103, USA.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Electrical and Computer Engineering Department, Texas A&M University, College Station, TX 77840, USA.
authors.forename: Zixiang
authors.initials: Z
authors.lastname: Xiong
authors.affiliation: Radiology Comprehensive Cancer Center Cancer Biology, Wake Forest University, Winston-Salem, NC 27103, USA.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Zhou
mesh_terms: D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics*; D059016:Tumor Microenvironment
chemical_list: D009363:Neoplasm Proteins; C576226:OCIAD2 protein, human; D016212:Transforming Growth Factor beta