Systematic Functional Annotation and Visualization of Biological Networks

Cell Syst. 2016 Jun 22;2(6):412-21. doi: 10.1016/j.cels.2016.04.014. Epub 2016 May 26.


Large-scale biological networks represent relationships between genes, but our understanding of how networks are functionally organized is limited. Here, I describe spatial analysis of functional enrichment (SAFE), a systematic method for annotating biological networks and examining their functional organization. SAFE visualizes the network in 2D space and measures the continuous distribution of functional enrichment across local neighborhoods, producing a list of the associated functions and a map of their relative positioning. I applied SAFE to annotate the Saccharomyces cerevisiae genetic interaction similarity network and protein-protein interaction network with gene ontology terms. SAFE annotations of the genetic network matched manually derived annotations, while taking less than 1% of the time, and proved robust to noise and sensitive to biological signal. Integration of genetic interaction and chemical genomics data using SAFE revealed a link between vesicle-mediate transport and resistance to the anti-cancer drug bortezomib. These results demonstrate the utility of SAFE for examining biological networks and understanding their functional organization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Databases, Genetic
  • Gene Ontology
  • Gene Regulatory Networks
  • Models, Biological*
  • Molecular Sequence Annotation
  • Protein Interaction Mapping
  • Protein Interaction Maps
  • Saccharomyces cerevisiae