Inference of Protein Complex Activities from Chemical-Genetic Profile and Its Applications: Predicting Drug-Target Pathways
Figure 2
Procedures for inferring the hidden activities of a collection of protein complexes in a cell.
(A) A bipartite network illustrating the first-order relationships between protein complexes (PCs) and strains they are associated with. The definitions of “protein complex”, “strains”, and “association” in the study are as follows: the first yeast comprehensive protein complexes reported by Gavin et al. [8] are used as a collection of “protein complexes” in a cell. The “strains” are defined as a collection of pooled deletion mutants released from Saccharomyces Genome Deletion Project [1]. The “association” is defined as the existence of physical or genetic interactions between at least one of components in PCs and knockout gene product of a strain. In bipartite network, we assume that the relative growth fitness of strains under different chemicals (called drugs or bioactive compounds in the text) is mainly caused by the deleterious associations of PCs and strains (Figure 1). (B) The bipartite PC-strain network reconstructed by applying PC-based Bayesian factor analysis (PCBA). The bar charts within dotted circles in the top of panel show the relative activities of PCs depending on chemicals inferred from our analysis. The bar charts within each strain in the bottom represent the relative growth fitness under different chemicals, which are used as observed data for our analysis. The thicknesses of arrows in the middle denote the association strength between PCs and strains inferred from our analysis. The colors of red and blue indicate “positive” and “negative” association, respectively. (C) It shows two types of input data for PCBA, one of which is a prior knowledge data of genetic and physical interactions in the left. It is represented in the form of matrix containing binary associations of each strain (row) to PCs (column) (called Z matrix in the text). If there was the association between the knockout gene of a strain i and at least one of components in a protein complex j, we set zij = 1. Otherwise we set zij = 0. The other is the chemical-genetic profiles representing relative growth fitness of pooled deletion strains under various chemicals. As the observed data for PCBA, it is shown in the right (called E matrix in the text).