Muscle-Atrophy-Multi-Omics-OSDR

Muscle Atrophy Countermeasures (Multi-Omics & Nutrition)

Multi-omics meta-analysis of spaceflight-induced muscle atrophy integrated with connectivity mapping (LINCS L1000), molecular docking, and a plant-based nutritional countermeasure optimization framework.

Overview

This repository hosts the data and analysis pipeline for re-deriving a consensus cross-species catabolic signature of spaceflight-induced muscle atrophy and translating these findings into evidence-based countermeasures. We integrate rodent and human spaceflight datasets from the NASA Open Science Data Repository (OSDR), perform connectivity mapping to identify counter-catabolic compounds, validate candidate nutraceuticals via molecular docking, and design optimized plant-based meal plans to meet muscle protein synthesis (MPS) thresholds.

Key Results

• Consensus Spaceflight Atrophy Signature: Re-derived a robust 141-gene cross-species catabolic signature (77 up-regulated, 64 down-regulated) across 10 OSDR studies (rodent spaceflight, human astronaut cfRNA, Inspiration4 crew blood, and bed rest analogs).
• Mitochondrial Dysfunction: The spaceflight signature is heavily dominated by the up-regulation of mitochondrial electron transport chain (ETC) genes (e.g., MT-ND1 through MT-ND6, MT-CO2, MT-CYB) and down-regulation of the master regulator PPARGC1A/PGC-1α.
• Connectivity Mapping (LINCS L1000): Screened 559 compounds and identified HMB, CoQ10, creatine, vitamin D3, and resveratrol as top candidates for reversing the spaceflight catabolic transcriptional program.
• Molecular Docking: Validated binding affinities of candidate compounds against key protein targets (e.g., resveratrol against SIRT1 and FOXO3; HMB against mTOR).
• Vegan Protein Benchmarking: Benchmarked 41 plant-based protein sources, identifying pea protein isolate (leucine 6.50g/100g, MPS score 2.25) and soy protein isolate (leucine 6.60g/100g, MPS score 2.11) as optimal sources for meeting the 2.5g leucine-per-meal threshold for MPS activation.

Repository Structure

Muscle-Atrophy-Multi-Omics-OSDR/
├── CITATION.cff          # Citation metadata
├── LICENSE               # MIT license
├── README.md             # This overview
├── Original_PLAN.md      # Project implementation plan
├── docs/                 # GitHub Pages landing page code
├── figures/              # SVG and PNG figures generated by the analysis
├── tables/               # Processed data, consensus signatures, and meal plans (CSV/JSON)
├── manuscript/           # Research article drafts and final report
│   ├── manuscript_npj_microgravity.md
│   └── report_muscle_atrophy_countermeasures.pdf
└── validation/           # Wet-lab protocol and Boltz molecular docking files
    ├── in_vitro_validation_protocol.md
    └── boltz_results_*/  # Sub-folders containing structural docking predictions

Datasets

The meta-analysis incorporates 10 datasets from NASA OSDR and GEO:

• Rodent Spaceflight: OSD-21, OSD-111, OSD-135, OSD-401, GSE213808
• Human Spaceflight: OSD-684 (tissue chip), OSD-530 (astronaut cfRNA), OSD-569 (Inspiration4 blood transcriptomics), OSD-571 (Inspiration4 plasma proteomics)
• Terrestrial Analog: OSD-370 (9-day bed rest)

Usage

All processed tables are available in the tables/ directory. Figures can be viewed in the figures/ folder. The raw data can be downloaded using the accessions listed in manuscript/manuscript_npj_microgravity.md.

License

• Code: MIT
• Manuscript, Figures, and Data: CC-BY-4.0

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