NASA EPSCoR R3: Causal Multivariate Network Analysis of Multi-Omics Datasets for Therapeutic Treatment of Muscle Atrophy in Mice, and Homosapiens in Microgravity

The goal of this proposal is to perform multi-study omics data integration of mice NASA GenLab datasets from the International Space Station (ISS), and predict muscle atrophy in microgravity, beneficial for diagnosis and therapeutic intervention for humans (Homosapiens) in spaceflight. Muscle atrophy is the wastage of muscle tissue that occurs due to aging, genetics, degenerative diseases and injuries. This condition is common among astronauts due to exposure to microgravity. Understanding the effects of novel therapies to treat muscle atrophy in mice is essential to provide similar treatments to human astronauts, as well as patients affected by this condition on Earth. Our study will focus on the analysis of Gene Regulatory Networks (GRNs) of mouse in space flight, and on Earth. Our current study has shown to be successful with the plant Arabidopsis Thaliana gene expression GLDS7, and GLDS120 datasets. Using graph based GRNs we will identify key gene players from these datasets, and identify gene signaling pathways that are associated with muscle and tissue degradation, ultimately leading us to GRN based therapeutics in spaceflight. Muscle atrophy and its treatments and drug-designs have been well studied on Earth, using GRNs, hence we will find correlates between the networks constructed on ground, with those on spaceflight. We will determine causal relations between the effects of therapy on ground, and on spaceflight using multivariate analysis.

The objectives for NASA Rapid Response Project are: 1) Analysis from flight and ground: Determine gene regulatory pathways, and common pathways in these networks using Fisher’s analysis. 2) Construct causal relational networks for muscle atrophy and its treatment, and implement probabilistic deep learning networks to predict the best therapies for muscle atrophy in spaceflight.

The Genelab datasets (GLDS-250, 249 246 245 247 248 243 244) and ground based GEO datasets (https://www.ncbi.nlm.nih.gov/gds) on muscle atrophy, and the effects of therapy, will be used to identify top most common pathways. A causal relational network analysis will be performed to predict the best treatment, and countermeasures for muscle atrophy in microgravity.

The causal networks, and the results of analysis generated by this project will be made available to the space biology research community. Dr. Nataniel Szewczyk, Professor of Nottingham Biomedical Research Centre, and Dr. Jonathan Galazka, Scientist from NASA Space Biosciences Research Branch will be collaborating in this project. They will be providing feedback, and insights in to the progress of this research activity. Their backgrounds in medicine, and biology will be indispensable for this project. This project will be conducted at the University of Puerto Rico (UPR), Mayaguez Campus and Rio Piedras Campus. The project team is interdisciplinary bringing together the PI, Dr. Manian a faculty in Electrical & Computer Engineering, and Bioengineering, and Co-PI, Dr. Janwa a faculty in Mathematics. This project is conducted in a Hispanic minority serving institution with 99% Hispanic students who will gain knowledge in the fields of space biology, mathematics, bioinformatics, and software tool development in Python, R, SageMath, and Cython (with resulting packages freely available for other scientists). This project will directly support two graduate students in Space Biology research, and involve many undergraduate students through course work and workshops. They will be exposed to NASA space related research. This project will also enable Hispanic minority students to take up internships with NASA Labs, and add to the workforce development for future NASA missions.

This is a mature technology (TRL 7+) — the realistic path in is usually NASA's Technology Transfer Program: licensing an existing NASA patent, or a Space Act Agreement to use NASA facilities/expertise directly. NASA also runs a startup licensing program with no upfront fee for companies formed to commercialize a specific NASA technology.

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