Cancer Institute A national cancer institute
designated cancer center

Atul Butte

Publication Details

  • Discovering functional relationships between RNA expression and chemotherapeutic susceptibility using relevance networks PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Butte, A. J., Tamayo, P., Slonim, D., Golub, T. R., Kohane, I. S. 2000; 97 (22): 12182-12186


    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.

    View details for Web of Science ID 000090071000086

    View details for PubMedID 11027309

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