Integrated Assembly: Physical, Genetic, and Functional Networks

Physical interactions represent direct binding events between molecules, such as binding between proteins and other proteins, proteins and DNA, proteins and drugs, and so on. In contrast, genetic interactions represent functional relationships between genes, in which the phenotypic output of one gene is modified by another. Both physical and genetic interaction mapping projects are progressing at a rapid pace using a variety of technologies. Although each technique provides a different slice of interaction data, all of these are reflections of the same biological process or disease. Both a major challenge and opportunity for Network Biology is to integrate these complementary large-scale views of biological function.

We are working on several approaches in this area:

  1. Methods to assemble and reconcile physical and genetic interactions within contiguous models.[Bandyopadhyay et al. Nature Methods doi:10.1038/nmeth.1506 2010; Hannum et al. PLoS Genetics 5(12):e1000782 2009; Bandyopadhyay et al. PLoS Compu Biol. 4(4):e1000065 2008; Kelley and Ideker Nature Biotechnology23(5):561-566 2005; Yeang et al. Genome Biology6(7): R62 2005]
  2. Integration of physical networks with gene expression data to reveal functional or “active modules” [Ideker et al. Bioinformatics18: S233. 2002].
  3. Using physical networks as a guide to identify genetic interactions within of genome-wide association studies [Hannum et al. PLoS Genetics 5(12):e1000782 2009].
  4. Increasing the coverage of each type of network. [Schwartz et al. Nature Methods 6(1):55-61 2009; Suthram et al. BMC Bioinformatics. 7(1):360 2006]

These efforts are funded by grants from the National Institute for General Medical Sciences and Microsoft.