Transcriptome alterations of mitochondrial and coagulation function in schizophrenia by cortical sequencing analysis

BMC Genomics

Research

Theresa Tsun-Hui Tsao¹  Sheng-An Lee²  Kuo-Chuan Huang³  Han Lin⁴  Ko-Chun Yang⁴ 

[1] Department of Biochemical Science and Technology, National Taiwan University, Taipei, Taiwan;Department of Information Management, Kainan University, Taoyuan, Taiwan;Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, Taipei, Taiwan;Department of Nursing, Ching Kuo Institute of Management and Health, Keelung, Taiwan;Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan;

关键词: Schizophrenia;    Candidate Gene;    Schizophrenic Patient;    Paliperidone;    Hedgehog Signaling Pathway;   

DOI  :  10.1186/1471-2164-15-S9-S6

来源: Springer

【 摘 要 】

BackgroundTranscriptome sequencing of brain samples provides detailed enrichment analysis of differential expression and genetic interactions for evaluation of mitochondrial and coagulation function of schizophrenia. It is implicated that schizophrenia genetic and protein interactions may give rise to biological dysfunction of energy metabolism and hemostasis. These findings may explain the biological mechanisms responsible for negative and withdraw symptoms of schizophrenia and antipsychotic-induced venous thromboembolism.We conducted a comparison of schizophrenic candidate genes from literature reviews and constructed the schizophrenia-mediator network (SCZMN) which consists of schizophrenic candidate genes and associated mediator genes by applying differential expression analysis to BA22 RNA-Seq brain data. The network was searched against pathway databases such as PID, Reactome, HumanCyc, and Cell-Map. The candidate complexes were identified by MCL clustering using CORUM for potential pathogenesis of schizophrenia.ResultsPublished BA22 RNA-Seq brain data of 9 schizophrenic patients and 9 controls samples were analyzed. The differentially expressed genes in the BA22 brain samples of schizophrenia are proposed as schizophrenia candidate marker genes (SCZCGs). The genetic interactions between mitochondrial genes and many under-expressed SCZCGs indicate the genetic predisposition of mitochondria dysfunction in schizophrenia. The biological functions of SCZCGs, as listed in the Pathway Interaction Database (PID), indicate that these genes have roles in DNA binding transcription factor, signal and cancer-related pathways, coagulation and cell cycle regulation and differentiation pathways.In the query-query protein-protein interaction (QQPPI) network of SCZCGs, TP53, PRKACA, STAT3 and SP1 were identified as the central "hub" genes. Mitochondrial function was modulated by dopamine inhibition of respiratory complex I activity. The genetic interaction between mitochondria function and schizophrenia may be revealed by DRD2 linked to NDUFS7 through protein-protein interactions of FLNA and ARRB2.The biological mechanism of signaling pathway of coagulation cascade was illustrated by the PPI network of the SCZCGs and the coagulation-associated genes. The relationship between antipsychotic target genes (DRD2/3 and HTR2A) and coagulation factor genes (F3, F7 and F10) appeared to cascade the following hemostatic process implicating the bottleneck of coagulation genetic network by the bridging of actin-binding protein (FLNA).ConclusionsIt is implicated that the energy metabolism and hemostatic process have important roles in the pathogenesis for schizophrenia. The cross-talk of genetic interaction by these co-expressed genes and reached candidate genes may address the key network in disease pathology. The accuracy of candidate genes evaluated from different quantification tools could be improved by crosstalk analysis of overlapping genes in genetic networks.

【 授权许可】

Unknown   
© Huang et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.