A Graph-Theoretic Study of Hepatitis C Infection Pathways in Humans using Protein-

Protein Interaction Networks

Anirban Mukhopadhyay
Department of Computer Science & Engineering
University of Kalyani
Kalyani-741235, West Bengal, India
Email: anirban@klyuniv.ac.in

Abstract

Hepatitis C, an infectious disease in humans, is caused by Hepatitis C virus (HCV)

which usually affects the liver. A number of studies indicate that the interactions
between HCV proteins and the human proteins play important role during this infection
and viral pathogenesis. System-level computational studies of viral pathogenesis using
protein-protein interaction (PPI) networks have been gaining popularity among the
computational biologists in recent time. In this talk, I shall discuss a recent study, where
we attempt to investigate the possible pathways of HCV infection using a network-
based study. We collect the PPI information between HCV and human proteins from a
public database called HCVpro to construct the HCV-Human PPI network. This
interaction network is represented as a bipartite graph, where two sets of vertices
denote HCV proteins and human proteins, respectively. The interactions are
represented as the edges of the graph. The bipartite HCV-Human PPI network is mined
to extract strong interaction modules or quasi-bicliques. Subsequently the human PPI
network is built using SRTING database and the same is clustered to find strong dense
modules or quasi-cliques which overlap with the quasi-bicliques identified in the
previous step. The human proteins involved in these quasi-cliques are considered as
the infection gateways. Biological relevance tests show that these gateway proteins are
biologically coherent and have high degrees in human PPI network compared to the
other virus-targeted proteins. Furthermore, the bipartite network representing the
association of human genes with various disease types is mined to extract the quasi-
bicliques which overlap with the gateway human proteins discovered in the preceding
stage. Thus we globally explore three networks, namely, HCV-human interaction
network, human protein interaction network, and human gene-disease association
network using graph-theoretic algorithms to discover the potential infection pathways
of HCV that lead to various diseases including different types of cancers. These
analyses help identify some key genes/proteins which play vital role during HCV
infection. These proteins can be considered as possible drug targets for more effective
anti-Hepatitis C therapeutics.