Cleavr tests candidate TNBC biomarkers against public sequencing data, subtype by subtype, with every claim independently re-derived and checked against the literature before it's published.
Triple-negative breast cancer (TNBC) is not one disease. Lehmann's 2011 classification split TNBC into distinct molecular subtypes: basal-like, mesenchymal, luminal androgen receptor, and others, each with different biology and different drug sensitivities. Despite that, candidate biomarker and targeting studies are still mostly done one gene, one paper, one lab at a time, without systematically checking whether a target behaves consistently across subtypes before it gets built into a therapeutic strategy.
Cleavr tests candidate TNBC biomarkers against public, patient-level sequencing data, starting with TCGA, broken out by molecular subtype, and cross-checks every claim against the primary literature before it's published. Every number is independently re-derived from raw source files in a second pass, not computed once and trusted. Null results get reported exactly as directly as positive ones.
Each entry below is independently re-derived from raw source data and cross-checked against the literature before publishing. Null results are reported as directly as positive ones.
Does the LHRH/GnRH receptor (GNRHR), the target of an active TNBC nanoparticle-targeting strategy, express differently across TNBC's molecular subtypes? If it does, that would matter for how consistently a receptor-targeted therapy could work across the disease's biological variants.
Result: no statistically significant difference across subtypes, and no relationship to survival in this cohort (TCGA), a real, well-caveated null result.
A gene-agnostic follow-up to Case Study 01: instead of testing one hand-picked gene, 15 candidates were sourced systematically from Open Targets' TNBC-associated target scores, then tested for subtype- and survival-association with Benjamini–Hochberg FDR correction applied across all 15 together, then scored on druggability (ChEMBL) and TNBC-specific literature coverage (PubMed).
The 8 FDR-significant genes were re-tested against METABRIC, a second, independent cohort (320 TNBC patients, nearly 3x the TCGA cohort) profiled on a different expression platform. 7 of 8 replicated on both. RRM2 did not (TCGA-significant, but p = 0.23 in METABRIC) and is reported as a miss, not dropped.
Status: computational only. Nothing here has been validated at the protein level yet, that's the next step, now underway with wet-lab flow cytometry.
Full methodology, data, and code for every case study are public.