The meta-analytical paradigm in an in silico hybrid: Pathways and networks perturbed during exposure to varying degrees of hypobaric hypoxia.

PURPOSE: Computational biology has opened a gateway to omics data analysis and shifted the focus from molecules to systemic molecular networks in the domain of hypobaric hypoxia (HH). Yet there are no meta-analytical investigations circumventing constraints such as organism (rat/human), HH exposure conditions (acute/chronic), and the tissues that can be investigated simultaneously in the realm of wet lab experiments.

EXPERIMENTAL DESIGN: We analyzed 154 differentially expressed proteins upon HH exposure using Ingenuity Pathway Analysis (IPA) tool, without the constraint of using a single organism or tissue type, to determine the most significant pathways and networks that are perturbed across a range of HH conditions.

RESULTS: We found acute phase response signaling, farsenoid X receptor/retinoid X receptor activation, liver X receptor/retinoid X receptor activation, clathrin-mediated endocytosis signaling, mitochondrial dysfunction, production of nitric oxide and ROS in macrophages, and integrin signaling to be the most significant universally perturbed pathways. Unique protein-function relationships have also been highlighted.

CONCLUSION AND CLINICAL RELEVANCE: This meta-analysis provides a list of specific pathways and networks across two model organisms that are perturbed due to HH exposure irrespective of its duration/intensity. Thus, it will be a map of important pathways and proteins to look at when exploring effects of HH exposure irrespective of tissue/organism chosen, particularly in the context of prophylactic/therapeutic targets.