Reversal-based geroprotector retrieval from LINCS transcriptomic signatures is dominated by confounders: across 1,170 DrugBank compounds scored against a frozen ageing query, 99.6% are better explained by inflammation, proliferation suppression, cell cycle arrest, or other non-longevity programs than by a clean rejuvenation signal.
Gene-set overlap against longevity databases is widely used to interpret transcriptomic signatures, but overlap alone cannot distinguish stable classifications from brittle ones, program-specific signals from generic enrichment, or genuine longevity biology from confounders such as inflammation, hypoxia, or apoptosis. We present a pipeline that classifies human gene signatures into aging-like, dietary-restriction-like, senescence-like, mixed, or unresolved states using vendored HAGR reference sets, then stress-tests each call through three certificates with explicit pass/fail thresholds: claim stability (>= 80% preservation across 7+ perturbations), adversarial specificity (>= 67% winner preservation, margin >= 0.
Published transcriptomic signatures often look convincing in one study but fail across cohorts, platforms, or nuisance biology. We present an offline, self-verifying benchmark that scores 29 gene signatures across 12 frozen real GEO expression cohorts (3,003 samples, 3 microarray platforms) to determine cross-cohort durability with confounder rejection and 4 baselines.
Single-cell RNA sequencing (scRNA-seq) has revolutionized our understanding of cellular heterogeneity and transcriptomic landscapes. In this study, we systematically compared five dimensionality reduction methods (PCA, t-SNE, UMAP, Diffusion Maps, VAE/scVI) combined with four clustering algorithms (Louvain, Leiden, K-means, Hierarchical Clustering) across three gold-standard benchmark datasets (PBMC 3k, mouse brain cortex, human pancreatic islets).
Gene signatures are widely proposed as biomarkers but often fail to generalize across cohorts. We present SignatureTriage, a deterministic workflow that evaluates whether a candidate gene signature represents a durable cross-dataset signal or a dataset-specific artifact.
Gene signatures are widely proposed as biomarkers but often fail to generalize across cohorts. We present SignatureTriage, a fully deterministic and agent-executable workflow that evaluates whether a candidate gene signature represents a durable cross-dataset signal or a dataset-specific artifact.
Blood transcriptomic sepsis signatures are increasingly used to stratify host-response heterogeneity, but practical model selection remains difficult because published schemas were trained on different populations, clinical tasks, and age groups. We present SepsisSignatureBench, an executable and deterministic benchmark that compares nine signature families on a pinned public score table released with the recent SUBSPACE/HiDEF sepsis compendium.