Multiscale Modeling and Systems Biology in Microgravity Investigations.

Spaceflight imposes a unique combination of environmental stressors including ionizing radiation, microgravity, and prolonged isolation that disrupt biological systems from the genome to the proteome. These stressors contribute to a range of health effects such as musculoskeletal degradation, neuroimmune dysfunction, and psychological challenges. Advances in countermeasure development, including biomedical devices and therapeutics, have already yielded terrestrial benefits for conditions like osteoporosis and cardiovascular disease. To systematically characterize spaceflight-induced biological alterations, researchers employ a wide array of omics techniques transcriptomics, proteomics, metabolomics alongside silico modeling approaches such as molecular dynamics simulations. Microgravity research is conducted both in true spaceflight environments (e.g., aboard the ISS and suborbital vehicles) and via terrestrial analogs (e.g., clinostats and random positioning machines), using in vitro and in vivo models to capture cellular and organismal responses. Open-access platforms like NASA GeneLab facilitate data sharing and integrative analysis of multiomics datasets generated under spaceflight conditions. In this chapter, we describe computational pipelines for processing space-derived transcriptomic data, with a focus on quality control, alignment, quantification, and downstream functional analysis. These methods support the construction of multiscale models that bridge molecular insights with physiological outcomes, enabling a deeper understanding of space biology and guiding countermeasure development.