Predicting Abdominal Aortic Aneurysm Target Genes by Level-2 Protein-Protein Interaction.
Abdominal aortic aneurysm (AAA) is frequently lethal and has no effective pharmaceutical treatment, posing a great threat to human health. Previous bioinformatics studies of the mechanisms underlying AAA relied largely on the detection of direct protein-protein interactions (level-1 PPI) between the products of reported AAA-related genes. Thus, some proteins not suspected to be directly linked to previously reported genes of pivotal importance to AAA might have been missed. In this study, we constructed an indirect protein-protein interaction (level-2 PPI) network based on common interacting proteins encoded by known AAA-related genes and successfully predicted previously unreported AAA-related genes using this network. We used four methods to test and verify the performance of this level-2 PPI network: cross validation, human AAA mRNA chip array comparison, literature mining, and verification in a mouse CaPO4 AAA model. We confirmed that the new level-2 PPI network is superior to the original level-1 PPI network and proved that the top 100 candidate genes predicted by the level-2 PPI network shared similar GO functions and KEGG pathways compared with positive genes.
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, P. R. China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, P. R. China.
Kexin
K
Zhang
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, P. R. China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, P. R. China.
Tuoyi
T
Li
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, P. R. China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, P. R. China.
Yi
Y
Fu
Department of Bioinformatics, School of Basic Medical Sciences, Peking University, Beijing, P. R. China.
Qinghua
Q
Cui
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, P. R. China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, P. R. China.
Wei
W
Kong
D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism* / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002130:Calcium Phosphates; D019295:Computational Biology; D057225:Data Mining; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D025941:Protein Interaction Mapping; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
D002130:Calcium Phosphates; D012333:RNA, Messenger; C020243:calcium phosphate