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Transcriptomic and Proteomic Data Integration and Two-Dimensional Molecular Maps with Regulatory and Functional Linkages: Application to Cell Proliferation and Invasion Networks in Glioblastoma
journal contribution
posted on 2015-12-04, 00:00 authored by Manoj
Kumar Gupta, Savita Jayaram, Divijendra Natha Reddy, Ravindra
Varma Polisetty, Ravi SirdeshmukhGlioblastoma multiforme (GBM), the
most aggressive primary brain
tumor, is characterized by high rates of cell proliferation, migration,
and invasion. New therapeutic strategies and targets are being continuously
explored with the hope for better outcome. By overlaying transcriptomic
and proteomic data from GBM clinical tissues, we identified 317 differentially
expressed proteins to be concordant with the messenger RNAs (mRNAs).
We used these entities to generate integrated regulatory information
at the level of microRNAs (miRNAs) and their mRNA and protein targets
using prediction programs or experimentally verified miRNA target
mode in the miRWalk database. We observed 60% or even more of the
miRNA–target pairs to be consistent with experimentally observed
inverse expression of these molecules in GBM. The integrated view
of these regulatory cascades in the contexts of cell proliferation
and invasion networks revealed two-dimensional molecular interactions
with regulatory and functional linkages (miRNAs and their mRNA–protein
targets in one dimension; multiple miRNAs associated in a functional
network in the second dimension). A total of 28 of the 35 differentially
expressed concordant mRNA–protein entities represented in the
proliferation network, and 51 of the 59 such entities represented
in the invasion network, mapped to altered miRNAs from GBM and conformed
to an inverse relationship in their expression. We believe the two-dimensional
maps of gene expression changes enhance the strength of the discovery
datasets derived from omics-based studies for their applications in
GBM as well as tumors in general.