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2017 ; 12
(11
): e0187091
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DiffSLC: A graph centrality method to detect essential proteins of a
protein-protein interaction network
#MMPMID29121073
Mistry D
; Wise RP
; Dickerson JA
PLoS One
2017[]; 12
(11
): e0187091
PMID29121073
show ga
Identification of central genes and proteins in biomolecular networks provides
credible candidates for pathway analysis, functional analysis, and essentiality
prediction. The DiffSLC centrality measure predicts central and essential genes
and proteins using a protein-protein interaction network. Network centrality
measures prioritize nodes and edges based on their importance to the network
topology. These measures helped identify critical genes and proteins in
biomolecular networks. The proposed centrality measure, DiffSLC, combines the
number of interactions of a protein and the gene coexpression values of genes
from which those proteins were translated, as a weighting factor to bias the
identification of essential proteins in a protein interaction network.
Potentially essential proteins with low node degree are promoted through
eigenvector centrality. Thus, the gene coexpression values are used in
conjunction with the eigenvector of the network's adjacency matrix and edge
clustering coefficient to improve essentiality prediction. The outcome of this
prediction is shown using three variations: (1) inclusion or exclusion of gene
co-expression data, (2) impact of different coexpression measures, and (3) impact
of different gene expression data sets. For a total of seven networks, DiffSLC is
compared to other centrality measures using Saccharomyces cerevisiae protein
interaction networks and gene expression data. Comparisons are also performed for
the top ranked proteins against the known essential genes from the Saccharomyces
Gene Deletion Project, which show that DiffSLC detects more essential proteins
and has a higher area under the ROC curve than other compared methods. This makes
DiffSLC a stronger alternative to other centrality methods for detecting
essential genes using a protein-protein interaction network that obeys
centrality-lethality principle. DiffSLC is implemented using the igraph package
in R, and networkx package in Python. The python package can be obtained from
git.io/diffslcpy. The R implementation and code to reproduce the analysis is
available via git.io/diffslc.