COMPASS: A Web-Based COMPosite Activity Scoring System to Navigate Health and Disease Through Deterministic Digital Biomarkers

Quantifying pathway activation in absolute, reproducible terms is central to systems biology and precision medicine. COMPASS (COMPosite Activity Scoring System) provides a deterministic, ontology-free framework that extracts gene-specific activation thresholds from expression data, standardizes deviation from these boundaries, and aggregates direction-encoded genes into per-sample composite activity scores. Implemented as an intuitive web application, COMPASS enables non-coding users to upload expression matrices, define custom gene sets, and instantly generate activity plots and ROC- AUC statistics for biological or clinical comparisons. Across diverse datasets, COMPASS yields stable, interpretable, and transferable digital biomarkers that benchmark the "humanness" of model systems, quantify differentiation or immune states, and track therapeutic response trajectories. By directly linking expression, threshold, deviation, and directionality, COMPASS replaces permutation-based enrichment with closed-form logic, delivering a transparent, mechanistic, and reproducible quantification system for pathway activity. Impact statementCOMPASS provides reproducible composite pathway activity scores from transcriptomic data, enabling standardized benchmarking across cohorts and model systems and accelerating translational biomarker evaluation.