Title:Systems Biology Approach for the Identification of Diagnostic and Therapeutic Targets in Medulloblastomas
VOLUME: 11 ISSUE: 2
Author(s):Aditi Kapoor, Vinayak Pachapur, Rekha Jain, Prateek Singh, Durairaj Renu, Jyoti Bajpai Dikshit and Sanjeeva Srivastava
Affiliation:Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai- 400 076, India.
Keywords:Cell lines, functional modules, medulloblastoma, molecular networks, personalized medicine, systems biology.
Abstract:Medulloblastomas are the most aggressive pediatric brain tumors originating from self-renewing common
progenitor cells and associated with high rate of invasion along with rapid spread. The hereditary origin of these tumors
can be studied to define it at genome level; however, to understand the molecular mechanism and pathogenesis, systems
level investigation is required. In this study we used systems level analysis to identify molecular targets, pathways,
molecular networks and functional modules associated with genes/proteins with altered expression in medulloblastoma.
Molecular functions, annotated functions, associated pathways, networks and functional modules were identified with
PANTHER, DAVID, Ingenuity Pathway Analysis, MetaCore and GeneSpring software analysis, respectively. P53
signaling, PI3K/AKT signaling, Notch signaling, Hedgehog signaling and HGF signaling were identified as significant
pathways, indicating the signature of molecules involved in medulloblastoma. Network analysis using IPA revealed new
set of molecules, HNRNPK, PDE4A, HES5, GSTP1, SLC16A2, and GADD45A, which also appeared as significant
functional modules in GeneSpring analysis. The systems biology approach used in this study provides a comprehensive
understanding of complex molecular alterations involved in medulloblastoma and reveals potential novel targets, which
could be used for future targeted or personalized therapeutic interventions.
