Research Papers:

Functional/activity network (FAN) analysis of gene-phenotype connectivity liaised by grape polyphenol resveratrol

Tze-chen Hsieh _, Sheng-Tang Wu, Dylan John Bennett, Barbara B. Doonan, Erxi Wu and Joseph M. Wu

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Oncotarget. 2016; 7:38670-38680. https://doi.org/10.18632/oncotarget.9578

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Tze-chen Hsieh1, Sheng-Tang Wu2, Dylan John Bennett1, Barbara B. Doonan1, Erxi Wu3,4,5, Joseph M. Wu1

1Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York 10595, U.S.A.

2Division of Urology, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC

3Department of Neurosurgery, Baylor Scott and White Health, Temple, Texas, 76508, U.S.A.

4Department of Surgery, Texas A&M College of Medicine, Temple, Texas 76504, U.S.A.

5Department of Pharmaceutical Sciences, Texas A&M Health Science Center, College Station, Texas 77843, U.S.A.

Correspondence to:

Tze-chen Hsieh, email: [email protected]

Keywords: resveratrol, functional/activity network analysis, connectivity, cancer

Received: December 23, 2015    Accepted: May 08, 2016    Published: May 24, 2016


Resveratrol is a polyphenol that has witnessed an unprecedented yearly growth in PubMed citations since the late 1990s. Based on the diversity of cellular processes and diseases resveratrol reportedly affects and benefits, it is likely that the interest in resveratrol will continue, although uncertainty regarding its mechanism in different biological systems remains.

We hypothesize that insights on disease-modulatory activities of resveratrol might be gleaned by systematically dissecting the publicly available published data on chemicals and drugs. In this study, we tested our hypothesis by querying DTome (Drug-Target Interactome), a web-based tool containing data compiled from open-source databases including DrugBank, PharmGSK, and Protein Interaction Network Analysis (PINA). Four direct protein targets (DPT) and 219 DPT-associated genes were identified for resveratrol. The DPT-associated genes were scrutinized by WebGestalt (WEB-based Gene SeT Analysis Toolkit). This enrichment analysis resulted in 10 identified KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways. Refined analysis of KEGG pathways showed that 2 — one linked to p53 and a second to prostate cancer — have functional connectivity to resveratrol and its four direct protein targets. These results suggest that a functional activity network (FAN) approach may be considered as a new paradigm for guiding future studies of resveratrol. FAN analysis resembles a BioGPS, with capability for mapping a Web-based scientific track that can productively and cost effectively connect resveratrol to its primary and secondary target proteins and to its biological functions.

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