title: Discovering functional relationships between RNA expression and chemotherapeutic susceptibility using relevance networks.
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.
authors.affiliation: Children's Hospital Informatics Program and Division of Endocrinology, Department of Medicine, Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA. atul_butte@harvard.edu
authors.forename: A J
authors.initials: AJ
authors.lastname: Butte
authors.forename: P
authors.initials: P
authors.lastname: Tamayo
authors.forename: D
authors.initials: D
authors.lastname: Slonim
authors.forename: T R
authors.initials: TR
authors.lastname: Golub
authors.forename: I S
authors.initials: IS
authors.lastname: Kohane
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D020869:Gene Expression Profiling; D006801:Humans; D005810:Multigene Family; D012334:RNA, Neoplasm / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D012334:RNA, Neoplasm