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2014 ; 30
(12
): i219-27
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New directions for diffusion-based network prediction of protein function:
incorporating pathways with confidence
#MMPMID24931987
Cao M
; Pietras CM
; Feng X
; Doroschak KJ
; Schaffner T
; Park J
; Zhang H
; Cowen LJ
; Hescott BJ
Bioinformatics
2014[Jun]; 30
(12
): i219-27
PMID24931987
show ga
MOTIVATION: It has long been hypothesized that incorporating models of network
noise as well as edge directions and known pathway information into the
representation of protein-protein interaction (PPI) networks might improve their
utility for functional inference. However, a simple way to do this has not been
obvious. We find that diffusion state distance (DSD), our recent diffusion-based
metric for measuring dissimilarity in PPI networks, has natural extensions that
incorporate confidence, directions and can even express coherent pathways by
calculating DSD on an augmented graph. RESULTS: We define three incremental
versions of DSD which we term cDSD, caDSD and capDSD, where the capDSD matrix
incorporates confidence, known directed edges, and pathways into the measure of
how similar each pair of nodes is according to the structure of the PPI network.
We test four popular function prediction methods (majority vote, weighted
majority vote, multi-way cut and functional flow) using these different matrices
on the Baker's yeast PPI network in cross-validation. The best performing method
is weighted majority vote using capDSD. We then test the performance of our
augmented DSD methods on an integrated heterogeneous set of protein association
edges from the STRING database. The superior performance of capDSD in this
context confirms that treating the pathways as probabilistic units is more
powerful than simply incorporating pathway edges independently into the network.
AVAILABILITY: All source code for calculating the confidences, for extracting
pathway information from KEGG XML files, and for calculating the cDSD, caDSD and
capDSD matrices are available from http://dsd.cs.tufts.edu/capdsd