title: A systems biology pipeline identifies new immune and disease related molecular signatures and networks in human cells during microgravity exposure.
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.
authors.affiliation: Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, Kolkata, 700064, India.
authors.forename: Sayak
authors.initials: S
authors.lastname: Mukhopadhyay
authors.affiliation: Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, Kolkata, 700064, India.
authors.forename: Rohini
authors.initials: R
authors.lastname: Saha
authors.affiliation: Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, Kolkata, 700064, India.
authors.forename: Anbarasi
authors.initials: A
authors.lastname: Palanisamy
authors.affiliation: Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, Kolkata, 700064, India.
authors.forename: Madhurima
authors.initials: M
authors.lastname: Ghosh
authors.affiliation: Department of Biological Sciences, Presidency University, Kolkata, 700073, India.
authors.forename: Anupriya
authors.initials: A
authors.lastname: Biswas
authors.affiliation: Department of Biological Sciences, Presidency University, Kolkata, 700073, India.
authors.forename: Saheli
authors.initials: S
authors.lastname: Roy
authors.affiliation: Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, Kolkata, 700064, India.
authors.forename: Arijit
authors.initials: A
authors.lastname: Pal
authors.affiliation: Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, Kolkata, 700064, India.
authors.forename: Kathakali
authors.initials: K
authors.lastname: Sarkar
authors.affiliation: Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, Kolkata, 700064, India.
authors.forename: Sangram
authors.initials: S
authors.lastname: Bagh
mesh_terms: D001249:Asthma / Q000235:genetics; D015551:Autoimmunity; D030541:Databases, Genetic; D003920:Diabetes Mellitus / Q000235:genetics; D015870:Gene Expression; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D007249:Inflammation / Q000235:genetics; D016328:NF-kappa B / Q000235:genetics; D009369:Neoplasms / Q000235:genetics; D051881:Receptor, Notch1 / Q000235:genetics; D015398:Signal Transduction; D049490:Systems Biology / Q000379:methods*; D014893:Weightlessness
chemical_list: D016328:NF-kappa B; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1