Predicting Abdominal Aortic Aneurysm Target Genes by Level-2 Protein-Protein Interaction

Kexin Zhang; Tuoyi Li; Yi Fu; Qinghua Cui; Wei Kong

doi:10.1371/journal.pone.0140888

Predicting Abdominal Aortic Aneurysm Target Genes by Level-2 Protein-Protein Interaction

PLoS One. 2015 Oct 23;10(10):e0140888. doi: 10.1371/journal.pone.0140888. eCollection 2015.

Authors

Kexin Zhang¹, Tuoyi Li¹, Yi Fu¹, Qinghua Cui², Wei Kong¹

Affiliations

¹ 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.
² Department of Bioinformatics, School of Basic Medical Sciences, Peking University, Beijing, P. R. China.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Aorta, Abdominal / metabolism*
Aorta, Abdominal / pathology
Aortic Aneurysm, Abdominal / chemically induced
Aortic Aneurysm, Abdominal / genetics*
Aortic Aneurysm, Abdominal / metabolism
Aortic Aneurysm, Abdominal / pathology
Calcium Phosphates
Computational Biology
Data Mining
Disease Models, Animal
Gene Expression Profiling
Humans
Mice
Mice, Inbred C57BL
Oligonucleotide Array Sequence Analysis
Protein Interaction Mapping
RNA, Messenger / genetics*
RNA, Messenger / metabolism
Transcription, Genetic*

Substances

Calcium Phosphates
RNA, Messenger
calcium phosphate

Grants and funding

This work was supported by funding from the National Program on Key Basic Research Projects (973 Program) (2010CB912504, 2012CB518002); the National Natural Science Foundation of the P. R. China (81121061, 91339000); National Science Fund for distinguished Young Scholars (81225002); International Cooperation and Exchanges NSFC (81220108004); and the “111” Project of Chinese Ministry of Education (No. B07001). All the fundings were received by WK. http://www.most.gov.cn/, http://www.moe.gov.cn/, http://www.nsfc.gov.cn/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.