Network rewiring in cancer: Applications to melanoma cell lines and the cancer genome atlas patients

Kuan Fu Ding, Darren Finlay, Hongwei Yin, William P.D. Hendricks, Chris Sereduk, Jeffrey Kiefer, Aleksandar D Sekulic, Patricia M. LoRusso, Kristiina Vuori, Jeffrey M. Trent, Nicholas J. Schork

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Genes do not work in isolation, but rather as part of networks that have many feedback and redundancy mechanisms. Studying the properties of genetic networks and how individual genes contribute to overall network functions can provide insight into genetically-mediated disease processes. Most analytical techniques assume a network topology based on normal state networks. However, gene perturbations often lead to the rewiring of relevant networks and impact relationships among other genes. We apply a suite of analysis methodologies to assess the degree of transcriptional network rewiring observed in different sets of melanoma cell lines using whole genome gene expression microarray profiles. We assess evidence for network rewiring in melanoma patient tumor samples using RNA-sequence data available from The Cancer Genome Atlas. We make a distinction between "unsupervised" and "supervised" network-based methods and contrast their use in identifying consistent differences in networks between subsets of cell lines and tumor samples. We find that different genes play more central roles within subsets of genes within a broader network and hence are likely to be better drug targets in a disease state. Ultimately, we argue that our results have important implications for understanding the molecular pathology of melanoma as well as the choice of treatments to combat that pathology.

Original languageEnglish (US)
Article number228
JournalFrontiers in Genetics
Volume9
Issue numberJUL
DOIs
StatePublished - Jul 10 2018
Externally publishedYes

Fingerprint

Atlases
Melanoma
Genome
Cell Line
Gene Regulatory Networks
Genes
Neoplasms
Molecular Pathology
Tumor Cell Line
Transcriptome
Pathology
Pharmaceutical Preparations

Keywords

  • Bioinformatics and computational biology
  • Data science
  • Drug interactions
  • Machine learning
  • Melanoma
  • Network rewiring
  • Pathway analysis
  • Simulation models

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Genetics(clinical)

Cite this

Ding, K. F., Finlay, D., Yin, H., Hendricks, W. P. D., Sereduk, C., Kiefer, J., ... Schork, N. J. (2018). Network rewiring in cancer: Applications to melanoma cell lines and the cancer genome atlas patients. Frontiers in Genetics, 9(JUL), [228]. https://doi.org/10.3389/fgene.2018.00228

Network rewiring in cancer : Applications to melanoma cell lines and the cancer genome atlas patients. / Ding, Kuan Fu; Finlay, Darren; Yin, Hongwei; Hendricks, William P.D.; Sereduk, Chris; Kiefer, Jeffrey; Sekulic, Aleksandar D; LoRusso, Patricia M.; Vuori, Kristiina; Trent, Jeffrey M.; Schork, Nicholas J.

In: Frontiers in Genetics, Vol. 9, No. JUL, 228, 10.07.2018.

Research output: Contribution to journalArticle

Ding, KF, Finlay, D, Yin, H, Hendricks, WPD, Sereduk, C, Kiefer, J, Sekulic, AD, LoRusso, PM, Vuori, K, Trent, JM & Schork, NJ 2018, 'Network rewiring in cancer: Applications to melanoma cell lines and the cancer genome atlas patients', Frontiers in Genetics, vol. 9, no. JUL, 228. https://doi.org/10.3389/fgene.2018.00228
Ding, Kuan Fu ; Finlay, Darren ; Yin, Hongwei ; Hendricks, William P.D. ; Sereduk, Chris ; Kiefer, Jeffrey ; Sekulic, Aleksandar D ; LoRusso, Patricia M. ; Vuori, Kristiina ; Trent, Jeffrey M. ; Schork, Nicholas J. / Network rewiring in cancer : Applications to melanoma cell lines and the cancer genome atlas patients. In: Frontiers in Genetics. 2018 ; Vol. 9, No. JUL.
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