Discovering functional relationships between RNA expression and chemotherapeutic susceptibility using relevance networks

Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):12182-6. doi: 10.1073/pnas.220392197.

Abstract

In an effort to find gene regulatory networks and clusters of genes that affect cancer susceptibility to anticancer agents, we joined a database with baseline expression levels of 7,245 genes measured by using microarrays in 60 cancer cell lines, to a database with the amounts of 5,084 anticancer agents needed to inhibit growth of those same cell lines. Comprehensive pair-wise correlations were calculated between gene expression and measures of agent susceptibility. Associations weaker than a threshold strength were removed, leaving networks of highly correlated genes and agents called relevance networks. Hypotheses for potential single-gene determinants of anticancer agent susceptibility were constructed. The effect of random chance in the large number of calculations performed was empirically determined by repeated random permutation testing; only associations stronger than those seen in multiply permuted data were used in clustering. We discuss the advantages of this methodology over alternative approaches, such as phylogenetic-type tree clustering and self-organizing maps.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Drug Screening Assays, Antitumor*
  • Gene Expression Profiling
  • Humans
  • Multigene Family
  • RNA, Neoplasm / genetics*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • RNA, Neoplasm