Integrated network analyses for functional genomic studies in cancer
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Wilson-2013-Integrated network a.pdf
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Author(s)
Fraenkel, Ernest
Wilson, Jennifer Lynn
Hemann, Michael
Lauffenburger, Douglas A
Date Issued
August 2013
Journal
Seminars in Cancer Biology
Publisher
Elsevier
Citation
Wilson, Jennifer L., Michael T. Hemann, Ernest Fraenkel, and Douglas A. Lauffenburger. “Integrated Network Analyses for Functional Genomic Studies in Cancer.” Seminars in Cancer Biology 23, no. 4 (August 2013): 213–218.
Version
Final published version
Abstract
RNA-interference (RNAi) studies hold great promise for functional investigation of the significance of genetic variations and mutations, as well as potential synthetic lethalities, for understanding and treatment of cancer, yet technical and conceptual issues currently diminish the potential power of this approach. While numerous research groups are usefully employing this kind of functional genomic methodology to identify molecular mediators of disease severity, response, and resistance to treatment, findings are generally confounded by “off-target” effects. These effects arise from a variety of issues beyond non-specific reagent behavior, such as biological cross-talk and feedback processes so thus can occur even with specific perturbation. Interpreting RNAi results in a network framework instead of merely as individual “hits” or “targets” leverages contributions from all hit/target contributions to pathways via their relationships with other network nodes. This interpretation can ameliorate dependence upon individual reagent performance and increase confidence in biological validation. Here we provide background on RNAi studies in cancer applications, review key challenges with functional genomics, and motivate the use of network models grounded in pathway analyses.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution
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DOI of Published Version
https://doi.org/10.1016/j.semcancer.2013.06.004
