wguesdon

Which pair of cell-surface proteins marks prostate cancer cells while sparing every healthy human cell type? Antigen-directed therapies are limited by on-target off-tumor toxicity; few antigens are absent from all normal tissue. We scored combinatorial surface-marker pairs, AND gates and NOT gates, per patient across a 24-patient localised prostate cancer atlas, against an assay-matched, donor-robust Tabula Sapiens reference and a matched benign-prostate control from the same tumors. The method recovers the preclinically validated PSMA-PSCA pair as a positive control: each antigen alone engages duodenum or bladder, and requiring both collapses the worst extra-prostatic co-detection roughly sixfold. It nominates one clean surface pair, PSMA × STEAP1 (both antigens have clinical binders; the pair is already a phase-1 dual ADC), and finds no usable NOT gate. An independent 369,000-cell cohort (HuPSA) confirms tumor-specificity but shows the pair covers AR-driven adenocarcinoma and is lost in metastatic and neuroendocrine disease. Claude Code drove the pipeline (datasets, containerised doublet removal and cohort conversion, uncertainty and label-leakage controls, a multi-agent report review); Claude Science added the literature survey and a GTEx and Protein Atlas protein-level safety cross-check. This is a reproducible, hypothesis-generating finding with a truth value, not a validated target. Links - Live site: https://base-by-base.com - Interactive explorer: https://base-by-base.com/explore - access code: 5OjDWJdAHq73BEqf5Y-xJQ - Demo video (3 min): https://www.youtube.com/watch?v=ejc4G0Y-WgE - Code (open-source, MIT): - Analysis + report: https://github.com/wguesdon/dual-marker-discovery - Website: https://github.com/wguesdon/dual-marker-discovery-site - Explorer app: https://github.com/wguesdon/dual-marker-discovery-app

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