SANTA: quantifying the functional content of molecular networks

PLoS Comput Biol. 2014 Sep 11;10(9):e1003808. doi: 10.1371/journal.pcbi.1003808. eCollection 2014 Sep.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Gene Regulatory Networks* / genetics
  • Gene Regulatory Networks* / physiology
  • Humans
  • Models, Biological*
  • Models, Molecular*
  • RNA Interference / physiology
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / physiology
  • Signal Transduction* / genetics
  • Signal Transduction* / physiology
  • Systems Biology / methods*