In Silico Comparative analysis of Cancer and Stem Cell Microarray data to demonstrate Molecular Transitions and the relative involvement of Glycolysis and Oxidative Phosphorylation cost-effective correlation of Bioenergetics and differentiation Processes -Applications In Drug Development

In the present study, we have validated the molecular switching between Glycolysis and Oxidative phosphorylation (OXPHOS) in certain cell types using open access in silico tools. Most of the cancers cells predominantly show higher rate of glycolysis (pyruvate formation) followed by lactic acid fermentation, in contrast with the predominant role of mitochondria in non- cancerous cells. This type of molecular switching is also noticed during the early stages of embryonic development, wherein the metabolic shift from OXPHOS to glycolysis occurs. Hence, it is necessary to study the switching between these pathways to most accurately replicate physiological conditions ex vivo/in vitro in differentiation/targeted differentiation-based studies. Further, an approach of this nature can help in further documenting the role of aberrations in cellular bioenergetics, contributing to neoplasia. A set of microarray datasets were selected from the NCBI GEO database, modelling three physiological conditions i.e., early development (stem cell), cancer, and Induced pluripotent cells (iPSCs). Data was analyzed using the 'R' software with packages imported from Bioconductor. Our results confirm the aforesaid switches/metabolic transitions in the selected data sets representing key cell types at various stages in the differentiation pathway. To the best of our knowledge, this is the first study of its kind wherein an in silico approach has been adopted to document/demonstrate the cellular, molecular transitions in two major metabolic pathways with ramifications in basic biology and drug development.

Author(s): Ayyappa Kumar S. K, Suresh P. K

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