A systems biology pipeline identifies new immune and disease related molecular signatures and networks in human cells during microgravity exposure.

Sayak Mukhopadhyay,Arijit Pal,Kathakali Sarkar,Sangram Bagh,Rohini Saha,Anupriya Biswas,Anbarasi Palanisamy,Saheli Roy,Madhurima Ghosh

doi:10.1038/srep25975

Sayak Mukhopadhyay, Arijit Pal + Show 7 more

Open Access

https://doi.org/10.1038/srep25975

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Abstract

Microgravity is a prominent health hazard for astronauts, yet we understand little about its effect at the molecular systems level. In this study, we have integrated a set of systems-biology tools and databases and have analysed more than 8000 molecular pathways on published global gene expression datasets of human cells in microgravity. Hundreds of new pathways have been identified with statistical confidence for each dataset and despite the difference in cell types and experiments, around 100 of the new pathways are appeared common across the datasets. They are related to reduced inflammation, autoimmunity, diabetes and asthma. We have identified downregulation of NfκB pathway via Notch1 signalling as new pathway for reduced immunity in microgravity. Induction of few cancer types including liver cancer and leukaemia and increased drug response to cancer in microgravity are also found. Increase in olfactory signal transduction is also identified. Genes, based on their expression pattern, are clustered and mathematically stable clusters are identified. The network mapping of genes within a cluster indicates the plausible functional connections in microgravity. This pipeline gives a new systems level picture of human cells under microgravity, generates testable hypothesis and may help estimating risk and developing medicine for space missions.

Highlights

Microgravity is a prominent health hazard for astronauts, yet we understand little about its effect at the molecular systems level
Using Gene Set Enrichment Analysis (GSEA) we have identified total 45 altered KEGG pathways (26 upregulated and 19 downregulated ) with p < 0.05 and high normalized enrichment score (NES) value
Enough human level data may not be available in near future as the number of astronauts flown to space is low

Summary

Introduction

Microgravity is a prominent health hazard for astronauts, yet we understand little about its effect at the molecular systems level. The network mapping of genes within a cluster indicates the plausible functional connections in microgravity This pipeline gives a new systems level picture of human cells under microgravity, generates testable hypothesis and may help estimating risk and developing medicine for space missions. This gene centric method cannot identify the downregulation of oxidative phosphorylation pathway in diabetes, where the mean decrease in member genes’ expression is about 1.2 folds[21,22] This is critical for the situation like microgravity, which results an overall low fold change in the global gene expression compare to other perturbation like cancers[23,24]. Pathways were assigned even when the fraction of mapped genes were as low as 2% of the whole pathway[14,20]

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