Spaceflight transcriptomic signatures & vegan nutritional countermeasures

A reproducible pipeline that builds consensus transcriptomic signatures from NASA OSDR rodent ISS RNA-seq studies, screens the LINCS L1000 perturbation compendium for compounds that reverse them ("opposite forcings"), validates hits with functional enrichment, and translates the results into a curated vegan nutrition layer organized by mission phase.

MIT (code)NASA OSDR LINCS L1000DESeq2 + metafor GSEA / ORAFooDB
Read the report (PDF) → Figures Pipeline code Code & data (GitHub)

Headline: across 15 meta-analyzed NASA OSDR rodent spaceflight studies (160 screened), consensus liver/immune (525 genes) and brain (505 genes) signatures were screened against LINCS L1000; the top brain reverser was vemurafenib (z = −9.68) and the top liver/immune reverser was imatinib. Ten bioactive nutrients were mapped to 12 vegan recipes across pre-/in-/post-flight mission phases.

Abstract

Spaceflight induces coordinated transcriptomic stress responses across tissues. This pipeline (1) enumerates and screens 160 NASA OSDR rodent ISS RNA-seq studies, meta-analyzing the 15 with usable differential-expression signal via DESeq2 per study and a random-effects (metafor) consensus across studies; (2) derives a 525-gene liver/immune signature (283 up, 242 down, 25 core) and a 505-gene brain signature (208 up, 297 down, 13 core); (3) screens the LINCS L1000 connectivity compendium — 219 liver/immune and 221 brain candidate compounds — for transcriptomic "opposite forcing" of each signature, annotated with DrugBank 5.1.8, the Broad Drug Repurposing Hub, and ChEMBL; (4) validates biological plausibility with GSEA/ORA (Hallmark, Reactome, GO BP) and JensenLab DISEASES enrichment; and (5) maps therapeutic hits onto FooDB + NutriChem 2.0 to surface 10 bioactive vegan nutrients, translated into 12 curated recipes organized by mission phase (pre-/in-/post-flight).

Highlights

Consensus signatures

525 liver/immune genes (283↑/242↓, 25 core) and 505 brain genes (208↑/297↓, 13 core) meta-analyzed across 15 of 160 screened OSDR studies.

Opposite-forcing screen

219 liver/immune and 221 brain LINCS L1000 candidate reversers; top hits imatinib (liver/immune) and vemurafenib (brain, z = −9.68).

Nutritional translation

10 bioactive vegan nutrients (incl. sulforaphane, quercetin, ascorbic acid) mapped from reversing compounds via FooDB.

Mission-phased recipes

12 curated vegan recipes; top nutrient coverage: Broccoli Sulforaphane Power Bowl (score 143).

Selected figures

Overview of the consensus liver/immune and brain signatures.
Fig 1 — Consensus signature overview (liver/immune vs. brain, up/down/core genes).
Top LINCS L1000 reversing compounds per tissue.
Fig 2 — Top LINCS L1000 reversing compounds per tissue signature.
GSEA Hallmark enrichment of the consensus signatures.
Fig 3 — GSEA Hallmark pathway enrichment.
Vegan nutrient coverage of the reversing compound set.
Fig 4 — Vegan nutrient coverage of the LINCS reverser set.
Nutrient coverage scores of the 12 curated vegan recipes.
Fig 5 — Recipe nutrient-coverage scores across mission phases.

Neurological companion analysis

A brain-focused reanalysis of the same rodent ISS transcriptomic data (OSD-525, OSD-564, OSD-612, OSD-613), pairing LINCS L1000 connectivity mapping with nutrient pharmacokinetic profiling to propose a phased, diet-based neuroprotection strategy.

Dominant pathology: mitochondrial dysfunction, protein-homeostasis failure and DNA-repair suppression, offset by upregulated synaptic/neuronal signaling. Top nutrient reversers by PK + LINCS evidence: sulforaphane (Nrf2 activator), ascorbic acid (BBB transport), quercetin (BBB integrity) — see figure legends for the full mechanistic detail, including the caveat that curcumin's oral bioavailability is ~1000× below its therapeutic target (Kroon et al. 2025).

Four-tier spaceflight brain injury mechanism cascade.
Spaceflight brain-injury mechanism cascade (stressors → cellular stress → molecular consequences → outcomes).
Nutrient-pathway-gene intervention network.
Nutrient–pathway–gene intervention network: 7 nutrients targeting 5 damaged pathways.
Diet-based neuroprotection strategy by mission phase.
Diet-neuroprotection strategy by mission phase (pre-/in-/post-flight).
Neurological report (PDF) → Neurological manuscript (LaTeX) Full neuro data/scripts bundle (.zip)

Data & code

Code is MIT-licensed; source data (NASA OSDR, LINCS L1000, DrugBank, ChEMBL, FooDB, JensenLab DISEASES) remain subject to their own licenses — see the Data Sources table in the README. Independent research; not affiliated with or endorsed by NASA.