title: High-resolution network biology: connecting sequence with function.
abstract: Proteins are not monolithic entities; rather, they can contain multiple domains that mediate distinct interactions, and their functionality can be regulated through post-translational modifications at multiple distinct sites. Traditionally, network biology has ignored such properties of proteins and has instead examined either the physical interactions of whole proteins or the consequences of removing entire genes. In this Review, we discuss experimental and computational methods to increase the resolution of protein-protein, genetic and drug-gene interaction studies to the domain and residue levels. Such work will be crucial for using interaction networks to connect sequence and structural information, and to understand the biological consequences of disease-associated mutations, which will hopefully lead to more effective therapeutic strategies.
authors.affiliation: 1] School of Medicine and Medical Science, University College Dublin, Dublin 4, Ireland. [2] Complex and Adaptive Systems Laboratory, University College Dublin, Dublin 4, Ireland.
authors.forename: Colm J
authors.initials: CJ
authors.lastname: Ryan
authors.forename: Peter
authors.initials: P
authors.lastname: Cimermančič
authors.forename: Zachary A
authors.initials: ZA
authors.lastname: Szpiech
authors.forename: Andrej
authors.initials: A
authors.lastname: Sali
authors.forename: Ryan D
authors.initials: RD
authors.lastname: Hernandez
authors.forename: Nevan J
authors.initials: NJ
authors.lastname: Krogan
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D019295:Computational Biology; D005786:Gene Expression Regulation / Q000187:drug effects*; D053263:Gene Regulatory Networks; D059647:Gene-Environment Interaction; D006801:Humans; D008957:Models, Genetic; D054730:Protein Interaction Domains and Motifs; D060066:Protein Interaction Maps; D017422:Sequence Analysis, DNA