overlake.bio

I built Spacefarer Phenome, a genetics-first computational drug-discovery pipeline for spaceflight physiological stress, anchored on bone mineral density (eBMD). A nine-stage funnel (phenotype, GWAS, druggable-genome, Mendelian randomization, PheWAS safety, druggability, structure, docking, MD) spends cheap CPU on the causal and safety stages before any GPU. The headline is an honest negative: the drug-target MR scan validated no target in the pre-registered set of 33 — an instrument-limited result, since key pQTL/eQTL panels were unreachable at run time, not a biological null; the positive control passed strongly (IVW p=1.85e-44). Cathepsin K, a pre-specified exemplar (not discovered here), was carried end-to-end to exercise the structural arm, re-ranking 24 known ChEMBL inhibitors with a conditional MD result. What matters is the rigor: pre-registered thresholds frozen in git, JSON-schema contracts between stages, per-artifact provenance, and an openly licensed, auditable record. Total GPU cost: $41.06.