IAC-09.A1.7.11. Computational Meta-Analysis of Differential Gene Expression in Spaceflight and Simulated Microgravity Conditions

摘要

To understand the essential features of biological regulatory pathways acting under the conditions of space flight and simulated microgravity, we designed and implemented computational framework for systematic meta-analysis of microarray datasets pooled from a number of related studies. Analysis was performed across multiple organisms and tissues including human, mouse, and yeast. Previously, the power of meta-analysis profiling using cDNA or DNA microarrays has been demonstrated by several group in the literature for a number of biological conditions including diseases and aging. To improve understanding of differentially expressed and co-expressed genes in microgravity (space flight) and space flight analog conditions, we developed computational method, comparative meta-profiling relying on cross-correlating over-represented functional categories of down- and up- regulated genes. We collected and analyzed 5 published microgravity and microgravity-analog data sets, comprising skeletal muscle and bone tissues of a mouse and T cells of a human, in addition to whole genome profiling of yeast. From this diverse collection of microarray data sets, we characterized common transcriptional profiles that are universally activated in multiple biological organisms and/or tissue samples in microgravity. Our results revealed common apoptosis and other cell-regulatory pathways. Biological regulatory pathways affected by microgravity include metabolic genes, immune system genes, cell cycle (cell cycle arrest) and mitotic (growth) divisions, DNA damage and repair, apoptosis pathways, stress responses, common signalling pathways.