title: Schizophrenia interactome with 504 novel protein-protein interactions.
abstract: Genome-wide association studies of schizophrenia (GWAS) have revealed the role of rare and common genetic variants, but the functional effects of the risk variants remain to be understood. Protein interactome-based studies can facilitate the study of molecular mechanisms by which the risk genes relate to schizophrenia (SZ) genesis, but protein-protein interactions (PPIs) are unknown for many of the liability genes. We developed a computational model to discover PPIs, which is found to be highly accurate according to computational evaluations and experimental validations of selected PPIs. We present here, 365 novel PPIs of liability genes identified by the SZ Working Group of the Psychiatric Genomics Consortium (PGC). Seventeen genes that had no previously known interactions have 57 novel interactions by our method. Among the new interactors are 19 drug targets that are targeted by 130 drugs. In addition, we computed 147 novel PPIs of 25 candidate genes investigated in the pre-GWAS era. While there is little overlap between the GWAS genes and the pre-GWAS genes, the interactomes reveal that they largely belong to the same pathways, thus reconciling the apparent disparities between the GWAS and prior gene association studies. The interactome including 504 novel PPIs overall, could motivate other systems biology studies and trials with repurposed drugs. The PPIs are made available on a webserver, called Schizo-Pi at http://severus.dbmi.pitt.edu/schizo-pi with advanced search capabilities.
authors.affiliation: Department of Biomedical Informatics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Intelligent Systems Program, School of Arts and Sciences, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Madhavi K
authors.initials: MK
authors.lastname: Ganapathiraju
authors.affiliation: Department of Biomedical Informatics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Intelligent Systems Program, School of Arts and Sciences, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Thahir
authors.affiliation: Department of Biomedical Informatics, School of Medicine, University of Pittsburgh , Pittsburgh, PA, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Handen
authors.affiliation: Department of Microbiology and Molecular Genetics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Cancer Virology Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
authors.forename: Saumendra N
authors.identifier: 0000-0002-2850-6121
authors.initials: SN
authors.lastname: Sarkar
authors.affiliation: Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Department of Neurology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Robert A
authors.identifier: 0000-0001-9154-9709
authors.initials: RA
authors.lastname: Sweet
authors.affiliation: Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Vishwajit L
authors.initials: VL
authors.lastname: Nimgaonkar
authors.affiliation: Immunomodulation Research Group, School of Biotechnology, Dublin City University , Dublin, Ireland.
authors.forename: Christine E
authors.initials: CE
authors.lastname: Loscher
authors.affiliation: Department of Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Bauer
authors.affiliation: Department of Biomedical Informatics, School of Medicine, University of Pittsburgh , Pittsburgh, PA, USA.
authors.forename: Srilakshmi
authors.initials: S
authors.lastname: Chaparala