Global view of a drug-sensitivity gene network
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Haixiu Yang1,*, Yunpeng Zhang1,*, Jiasheng Wang1, Tan Wu1, Siyao Liu1, Yanjun Xu1 and Desi Shang1
1College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China
*These authors contributed equally to this work
Desi Shang, email: [email protected]
Yanjun Xu, email: [email protected]
Keywords: drug; sensitivity gene; network; enrichment analysis; network analysis
Received: August 30, 2017 Accepted: November 16, 2017 Published: December 14, 2017
An important challenge in drug development is to gain insight into the mechanism of drug sensitivity. Looking for insights into the global relationships between drugs and their sensitivity genes would be expected to reveal mechanism of drug sensitivity. Here we constructed a drug-sensitivity gene network (DSGN) based on the relationships between drugs and their sensitivity genes, using drug screened genomic data from the NCI-60 cell line panel, including 181 drugs and 1057 sensitivity genes, and 1646 associations between them. Through network analysis, we found that two drugs that share the same sensitivity genes tend to share the same Anatomical Therapeutic Chemical classification and side effects. We then found that the sensitivity genes of same drugs tend to cluster together in the human interactome and participate in the same biological function modules (pathways). Finally, we noticed that the sensitivity genes and target genes of the same drug have a significant dense distance in the human interactome network and they were functionally related. For example, target genes such as epidermal growth factor receptor gene can activate downstream sensitivity genes of the same drug in the PI3K/Akt pathway. Thus, the DSGN would provide great insights into the mechanism of drug sensitivity.
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