title: SANTA: quantifying the functional content of molecular networks.
abstract: Linking networks of molecular interactions to cellular functions and phenotypes is a key goal in systems biology. Here, we adapt concepts of spatial statistics to assess the functional content of molecular networks. Based on the guilt-by-association principle, our approach (called SANTA) quantifies the strength of association between a gene set and a network, and functionally annotates molecular networks like other enrichment methods annotate lists of genes. As a general association measure, SANTA can (i) functionally annotate experimentally derived networks using a collection of curated gene sets and (ii) annotate experimentally derived gene sets using a collection of curated networks, as well as (iii) prioritize genes for follow-up analyses. We exemplify the efficacy of SANTA in several case studies using the S. cerevisiae genetic interaction network and genome-wide RNAi screens in cancer cell lines. Our theory, simulations, and applications show that SANTA provides a principled statistical way to quantify the association between molecular networks and cellular functions and phenotypes. SANTA is available from http://bioconductor.org/packages/release/bioc/html/SANTA.html.
authors.affiliation: Department of Life Sciences, Imperial College London, London, United Kingdom.
authors.forename: Alex J
authors.initials: AJ
authors.lastname: Cornish
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, Cambridgeshire, United Kingdom.
authors.forename: Florian
authors.initials: F
authors.lastname: Markowetz
mesh_terms: D045744:Cell Line, Tumor; D053263:Gene Regulatory Networks / Q000235:genetics / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D034622:RNA Interference / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D049490:Systems Biology / Q000379:methods*