Confirming an integrated pathology of diabetes and its complications by molecular biomarker-target network analysis

Zhao,Zide; Zhang,Yingying; Gai,Fengchun; Wang,Ying

doi:10.3892/mmr.2016.5478

Confirming an integrated pathology of diabetes and its complications by molecular biomarker-target network analysis

Authors:
- Zide Zhao
- Yingying Zhang
- Fengchun Gai
- Ying Wang
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Affiliations: Department of Neuro‑Ophthalmology, Eye Hospital, China Academy of Chinese Medical Sciences, Beijing 100040, P.R. China, Laboratory of Pharmacology, Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, P.R. China, Department of Infection Control, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin 130021, P.R. China
Published online on: July 7, 2016 https://doi.org/10.3892/mmr.2016.5478
Pages: 2213-2221

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Abstract

Despite ongoing research into diabetes and its complications, the underlying molecular associations remain to be elucidated. The systematic identification of molecular interactions in associated diseases may be approached using a network analysis strategy. The biomarker-target interrelated molecules associated with diabetes and its complications were identified via the Comparative Toxicogenomics Database (CTD); the Search Tool for Recurring Instances of Neighboring Genes was utilized for network construction. Functional enrichment analysis was performed with Database for Annotation, Visualization and Integrated Discovery software to investigate connections between diabetes and its complications. A total of 142 (including 122 biomarkers, 10 therapeutic targets and 10 overlapping molecules) biomarker-target interrelated molecules associated with diabetes and its complications were identified via the CTD database, and analysis of the network yielded 1,087 biological processes and fifteen Kyoto Encyclopedia of Genes and Genomes pathways with significant P‑values. Various critical aspects of the networks were examined in the present study: a) Intermolecular horizontal and vertical combinations in biomarkers and therapeutic targets associated with diabetes and its complicationb) network topology properties associated with molecular pathological responsec) contribution of key molecules to integrated regulation; and d) crosstalk between multiple pathways. Based on a multi-dimensional analysis, it was concluded that the integrated molecular pathological development of diabetes and its complications does not proceed randomly, which suggests a requirement for integrated, multi-target intervention.

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