  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 \emph{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.
