Title

Authors

Affiliation

¹Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan; ²Tohoku Medical Megabank Organization, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai Miyagi, 980-8573, Japan; ³Graduate School of Biomedical Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan

Email

takai@megabank.tohoku.ac.jp; *Corresponding author

Article Type

Hypothesis

Date

Received December 06, 2014; Revised January 14, 2015; Accepted January 15, 2015; Published April 30, 2015

Bipolar disorder (BD) is a psychiatric disease considered to polygenic with multiple factors in genetics, each of which is not dominant but collaborative during pathogenic progression. We describe a method that estimates the collaborative contribution to the disease between a certain well-studied pathway and the other candidate pathway using Gene Set Enrichment Analysis (GSEA). We describe a modified GSEA (improved derivation) to identify genes that are significantly and differentially expressed between disease and non-disease states and that are consistently co-expressed with a target pathway which is deeply related to disease etiology. The modified GSEA uses available gene expression data to identify molecular mechanism (ubiquitin-proteasome and inflammatory response) associated with the disease. We believe that this approach could reveal hidden relations between a certain well-studied pathway and the other candidate pathway known in literature.

Abbreviations

ATP5I, ATP synthase H+ transporting mitochondrial F0 complex subunit E; ATP5J, ATP synthase H+ transporting mitochondrial F0 complex subunit F6; BAD, Bcl-2-associated death promoter; BAX, Bcl-2-associated x protein; Bcl-2, B-cell lymphoma 2; BDNF, brain derived neurotrophic factor; COX5B, Cytochrome c oxidase subunit Vb; COX7A2, cytochrome c oxidase subunit VIIa polypeptide 2; DLK, dual leucine zipper-bearing kinase ; GABA, Gamma aminobutyric acid; IL-8, Interleukin 8; NDUFA1, NADH dehydrogenase 1 alpha subcomplex 1; NDUFB2, NADH dehydrogenase1 beta subcomplex 2; NDUFS4, NADH dehydrogenase Fe-S protein 4; NGF, nerve growth factor; PPP2R5C, protein phosphatase 2 regulatory subunit B gamma; PSMA3, proteasome subunit alpha type 3; PSMA7, proteasome subunit alpha type 7; PSMB1, proteasome subunit beta type 1; PSMB6, proteasome subunit beta type 6; PSMB7, proteasome subunit beta type 7; PSMC2, proteasome 26S subunit ATPase 2; PSMC5, proteasome 26S subunit ATPase 5; SLC6A4, solute carrier family 6 member 4; TNFa, tumor necrosis factor a; UBE2A, ubiquitin-conjugating enzyme E2A; UCRC, ubiquinol-cytochrome c reductase complex; UFC1, ubiquitin-fold modifier conjugating enzyme 1; UQCRQ, ubiquinol-cytochrome c reductase complex III subunit VII; USP14, ubiquitin specific protease 14.

Citation

Sawai et al. Bioinformation 11(4): 207-216 (2015)

Edited by

P Kangueane

ISSN

0973-2063

Publisher

Biomedical Informatics

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.