HPV integration associated genome-wide disruption - A functional and network analysis

Amit Kumar Gupta, Manoj Kumar*

Bioinformatics Centre, CSIR-Institute of Microbial Technology, Sector 39A, Chandigarh-160036, India
Email: amitg@imtech.res.in, manojk@imtech.res.in
About

Results

Human papillomaviruses (HPVs) are the small circular double-stranded DNA

onco-viruses known to play a crucial role in the progression and etiology of
cervical cancer, head and neck squamous cell carcinomas (HNSCCs), and
many more.
Viral integration is a key incident in hpv-mediated carcinogenesis, which leads
to the disruption of various key cellular genes. Thus, contributes in aberrant
proliferation, genomic instability i.e. structural alterations, translocations, large
deletions etc., cellular immortalization and enhance malignant progression.
In this study, we have performed a systematic meta-analysis of 463 disrupted
genes due to integration events that might be expedient to support cancer
biomarker discovery.
Our integrative functional and biological network analysis identify distinct
pattern or modules associated with various biological processes, protein
classes, pathways, molecular functions in the context of gene ontology, coexpression, co-localization, protein-protein interactions etc.
Integrative network in grid layout representing functional association and interaction of HPVs mediated disrupted genes.
Each node represent a gene, Color of each node is based on score range, Edges are shown in distinct colors based on
association type

Materials and Methods

Distinct molecular functions and number of genes

Distribution of genes in different cellular

components

xyz
Overrepresented
Hypergeometric test
FDR correction
Significance level - 0.05

Gene ontology (GO) based clustering of genes visualizing overrepresented GO categories

after Benjamini & Hochberg false discovery rate (FDR) correction

Bar diagram illustrating distribution of biological processes

Conclusions
Overall, 463 disrupted genes (unique) due to integration events were analyzed to provide
global insights of their system level properties.

Acknowledgement
Council of Scientific and Industrial Research (CSIR), India (BSC0121) and Department of
Biotechnology (DBT), Government of India (GAP0001).

Most of the genes are interrelated with tumor development and various regulatory processes
mainly binding, cell differentiation, DNA repair mechanisms, apoptosis, signaling and so on,
that could jointly become involved in viral induced oncogenesis.
These findings may be helpful to accelarate clinical biomarker discovery for HPV mediated
carcinomas.

Categorization of disrupted genes in different protein classes along with IDs

Bar diagram representing pathway distribution

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