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

Butte AJ, Tamayo P, Slonim D, Golub TR, Kohane IS. Discovering functional relationships between RNA expression and chemotherapeutic susceptibility using relevance networks. Proc Natl Acad Sci U S A. 2000;97:12182–6.

NOTES

Butte, A JTamayo, PSlonim, DGolub, T RKohane, I SengT15 LM007092/LM/NLM NIH HHS/5T15 LM07092-07/LM/NLM NIH HHS/R01 LM06587-01/LM/NLM NIH HHS/Research Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.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.
Last updated on 02/17/2021