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Using Functional Signature Ontology (FUSION) to Identify Mechanisms of Action for Natural Products

Authors
 Malia B. Potts  ;  Hyun Seok Kim  ;  Kurt W. Fisher  ;  Youcai Hu  ;  Yazmin P. Carrasco  ;  Gamze Betul Bulut  ;  Yi-Hung Ou  ;  Mireya L. Herrera-Herrera  ;  Federico Cubillos  ;  Saurabh Mendiratta  ;  Guanghua Xiao  ;  Matan Hofree  ;  Trey Ideker  ;  Yang Xie  ;  Lily Jun-shen Huang  ;  Robert E. Lewis  ;  John B. MacMillan  ;  Michael A. White 
Citation
 SCIENCE SIGNALING, Vol.6(297) : 90, 2013 
Journal Title
 SCIENCE SIGNALING 
ISSN
 1937-9145 
Issue Date
2013
MeSH
Animals ; Autophagy/drug effects ; Autophagy/genetics ; Bacteria/chemistry ; Bacteria/classification ; Biological Products/chemistry ; Biological Products/isolation & purification ; Biological Products/pharmacology* ; Cell Line, Tumor ; Cells, Cultured ; Cluster Analysis ; Computational Biology/methods ; Drug Evaluation, Preclinical/methods ; Gene Expression Regulation, Neoplastic/drug effects* ; Gene Ontology* ; Gene Regulatory Networks/drug effects ; Gene Regulatory Networks/genetics ; HCT116 Cells ; Humans ; Invertebrates/chemistry ; MCF-7 Cells ; Marine Biology ; Mice ; Mice, Inbred BALB C ; MicroRNAs/genetics ; Molecular Structure ; Oligonucleotide Array Sequence Analysis ; RNA Interference ; Transcriptome/drug effects*
Keywords
Animals ; Autophagy/drug effects ; Autophagy/genetics ; Bacteria/chemistry ; Bacteria/classification ; Biological Products/chemistry ; Biological Products/isolation & purification ; Biological Products/pharmacology* ; Cell Line, Tumor ; Cells, Cultured ; Cluster Analysis ; Computational Biology/methods ; Drug Evaluation, Preclinical/methods ; Gene Expression Regulation, Neoplastic/drug effects* ; Gene Ontology* ; Gene Regulatory Networks/drug effects ; Gene Regulatory Networks/genetics ; HCT116 Cells ; Humans ; Invertebrates/chemistry ; MCF-7 Cells ; Marine Biology ; Mice ; Mice, Inbred BALB C ; MicroRNAs/genetics ; Molecular Structure ; Oligonucleotide Array Sequence Analysis ; RNA Interference ; Transcriptome/drug effects*
Abstract
A challenge for biomedical research is the development of pharmaceuticals that appropriately target disease mechanisms. Natural products can be a rich source of bioactive chemicals for medicinal applications but can act through unknown mechanisms and can be difficult to produce or obtain. To address these challenges, we developed a new marine-derived, renewable natural products resource and a method for linking bioactive derivatives of this library to the proteins and biological processes that they target in cells. We used cell-based screening and computational analysis to match gene expression signatures produced by natural products to those produced by small interfering RNA (siRNA) and synthetic microRNA (miRNA) libraries. With this strategy, we matched proteins and miRNAs with diverse biological processes and also identified putative protein targets and mechanisms of action for several previously undescribed marine-derived natural products. We confirmed mechanistic relationships for selected siRNAs, miRNAs, and compounds with functional roles in autophagy, chemotaxis mediated by discoidin domain receptor 2, or activation of the kinase AKT. Thus, this approach may be an effective method for screening new drugs while simultaneously identifying their targets.
Full Text
http://stke.sciencemag.org/content/6/297/ra90.long
DOI
10.1126/scisignal.2004657
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Kim, Hyun Seok(김현석) ORCID logo https://orcid.org/0000-0003-4498-8690
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/89207
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