The Space Omics and Medical Atlas (SOMA) and international astronaut biobank.

Spaceflight induces molecular, cellular and physiological shifts in astronauts and poses myriad biomedical challenges to the human body, which are becoming increasingly relevant as more humans venture into space1-6. Yet current frameworks for aerospace medicine are nascent and lag far behind advancements in precision medicine on Earth, underscoring the need for rapid development of space medicine databases, tools and protocols. Here we present the Space Omics and Medical Atlas (SOMA), an integrated data and sample repository for clinical, cellular and multi-omic research profiles from a diverse range of missions, including the NASA Twins Study7, JAXA CFE study8,9, SpaceX Inspiration4 crew10-12, Axiom and Polaris. The SOMA resource represents a more than tenfold increase in publicly available human space omics data, with matched samples available from the Cornell Aerospace Medicine Biobank. The Atlas includes extensive molecular and physiological profiles encompassing genomics, epigenomics, transcriptomics, proteomics, metabolomics and microbiome datasets, which reveal some consistent features across missions, including cytokine shifts, telomere elongation and gene expression changes, as well as mission-specific molecular responses and links to orthologous, tissue-specific mouse datasets. Leveraging the datasets, tools and resources in SOMA can help to accelerate precision aerospace medicine, bringing needed health monitoring, risk mitigation and countermeasure data for upcoming lunar, Mars and exploration-class missions.

AOC: Analysis of Orthologous Collections - an application for the characterization of natural selection in protein-coding sequences.

Motivation: Modern molecular sequence analysis increasingly relies on automated and robust software tools for interpretation, annotation, and biological insight. The Analysis of Orthologous Collections (AOC) application automates the identification of genomic sites and species/lineages influenced by natural selection in coding sequence analysis. AOC quantifies different types of selection: negative, diversifying or directional positive, or differential selection between groups of branches. We include all steps necessary to go from unaligned homologous sequences to complete results and interactive visualizations that are designed to aid in the useful interpretation and contextualization. Results: We are motivated by a desire to make evolutionary analyses as simple as possible, and to close the disparity in the literature between genes which draw a significant amount of interest and those that are largely overlooked and underexplored. We believe that such underappreciated and understudied genetic datasets can hold rich biological information and offer substantial insights into the diverse patterns and processes of evolution, especially if domain experts are able to perform the analyses themselves. Availability and implementation: A Snakemake [Mölder et al., 2021] application implementation is publicly available on GitHub at https://github.com/aglucaci/AnalysisOfOrthologousCollections and is accompanied by software documentation and a tutorial.

The evolution of mammalian Rem2: unraveling the impact of purifying selection and coevolution on protein function, and implications for human disorders.

Rad And Gem-Like GTP-Binding Protein 2 (Rem2), a member of the RGK family of Ras-like GTPases, is implicated in Huntington's disease and Long QT Syndrome and is highly expressed in the brain and endocrine cells. We examine the evolutionary history of Rem2 identified in various mammalian species, focusing on the role of purifying selection and coevolution in shaping its sequence and protein structural constraints. Our analysis of Rem2 sequences across 175 mammalian species found evidence for strong purifying selection in 70% of non-invariant codon sites which is characteristic of essential proteins that play critical roles in biological processes and is consistent with Rem2's role in the regulation of neuronal development and function. We inferred epistatic effects in 50 pairs of codon sites in Rem2, some of which are predicted to have deleterious effects on human health. Additionally, we reconstructed the ancestral evolutionary history of mammalian Rem2 using protein structure prediction of extinct and extant sequences which revealed the dynamics of how substitutions that change the gene sequence of Rem2 can impact protein structure in variable regions while maintaining core functional mechanisms. By understanding the selective pressures, protein- and gene - interactions that have shaped the sequence and structure of the Rem2 protein, we gain a stronger understanding of its biological and functional constraints.