Secretome Profiling Reveals Acute Changes in Oxidative Stress, Brain Homeostasis, and Coagulation Following Short-Duration Spaceflight

As more and more organizations set their sights on life in space, the realm of space travel will rapidly evolve and offer unprecedented accessibility to those eager to experience it. However, amidst this thrilling progress, there are a myriad of biomedical challenges facing spaceflight crews that need to be addressed to ensure astronaut well-being and the success and sustainability of human space exploration.

To truly advance aerospace health and medicine, large, detailed multi-omics astronaut profile databases are required to help researchers fully understand the physiological changes that occur to the human body in space.

Looking to gain new insights and build on learnings from prior missions, a Weill Cornell Medicine research team, led by Christopher Mason, Ph.D., took the incredible opportunity to analyze the all-civilian cohort of SpaceX’s 2021 Inspiration4 (I4) mission, using among its chosen technologies, Seer’s Proteograph™ technology.

With the help of the Proteograph’s unparalleled throughput, sensitivity, and scalability, they successfully revealed new spaceflight data, while comparing and extending findings from other missions compiled in the Space Omics and Medical Atlas (SOMA). The Proteograph provided novel, unbiased insights into proteomic changes, offering deeper understanding of the physiological responses that occur to astronauts and human biology and helping advance the discovery of novel biomarkers and the development of precision medicines across a range of research sectors.

Today, SOMA, the sample repository for clinical, cellular, and multi-omics profiles, is the first-of-its-kind, largest molecular roadmap for spaceflight impact on the human body and it now includes plasma proteomic data generated from Seer’s Proteograph workflow.

The Study Design

Using recently developed protocols, the I4 crew participated in a range of biospecimen collections before, during, and after their 590km-high, three-day orbital mission in a SpaceX Dragon capsule.

The 2,911 I4 biospecimen samples – spanning spatial transcriptomics data, long-read RNA profiles, microbiome data, exosome profiles, and immune diversity maps – were then profiled for spaceflight impact (e.g., microgravity and high radiation) on the crew’s physiology and health.

Using the Proteograph, the research team was able to analyze individual responses to spaceflight from proteomic, transcriptomic, and microbiome data. They conducted rigorous dataset annotations and comparisons with prior missions and spaceflight control datasets compiled in SOMA, helping examine the dynamics of gene, protein, and metabolites. (The other missions included Polaris Dawn, Axiom-2, the NASA Twin Study, and the Japanese Aerospace Exploration Agency (JAXA) Cell-Free Epigenome (CFE) project.)

The Results

The data and samples Weill Cornell Medicine generated using the Proteograph offered an unprecedented view of the multi-system ‘omics changes in astronauts during and after spaceflight. The workflow’s proteomic plasma profiling helped reveal the range of molecular variation across biological pathways, by crew member, providing novel insights into the changes that occur to the human body from spaceflight.

Now representing a >10-fold increase in total publicly available omics data and including data generated by Seer technology, SOMA serves not only as a resource for the life sciences and aerospace communities to study aerospace-associated physiological changes but also as an integrative ‘omics framework to guide future spaceflight studies and inform precision space health systems.

The Proteograph continues to demonstrate how its workflow offers scientists a deeper understanding of physiological responses and biology, helping advance the development of novel biomarkers and precision medicines across a wider range of research sectors.