DUAL-REGISTERED PROTOCOL // OSF PRE-REGISTERED (DOI: 10.17605/OSF.IO/VPS9D) · CLINICALTRIALS.GOV PRS IN PROGRESS · PROTOCOL ID: DS-CLIN-2026-RARE-RESOLVE · PLANNED N = 10,000
RARE-RESOLVE™ Registry.
Ending the diagnostic odyssey for orphan disease.
Over 350 million individuals worldwide live with a rare disease, facing an average 7-year diagnostic odyssey with over 8 misdiagnoses. RARE-RESOLVE™ is an observational DCT registry ($N=10,000$) applying Human Phenotype Ontology (HPO) deep graphs, whole-genome trio re-analysis, and DNA methylation epi-signatures under the DeepSensi Cognitive Engine. Participation in the clinical registry is 100% Free.
RESOLVE in the United States: in preparation (IRB submission in preparation, the first country to open).
Registry Strata
Three Core Orphan Disease Cohorts
Undiagnosed Multi-System Syndromes
Pediatric and young adult patients with severe multi-organ dysfunction who remain without a definitive diagnosis following negative or inconclusive standard WES/WGS. High-dimensional HPO phenome graph synthesis under DSS-001.
Ultra-Rare Mendelian & N=1 Mutations
Orphan monogenic diseases with fewer than 1,000 documented cases worldwide (OMIM/Orphanet/EURORDIS). Modeling non-coding regulatory mutations, deep intronic splice variants, and structural copy number variations (CNVs).
Episignature & Chromatin Remodeling Disorders
Imprinting defects, SWI/SNF complexopathies, and chromatin remodeling mutations. Genome-wide DNA methylation profiling (Epi-signatures) to classify variants of uncertain significance (VUS).
From routine care, ordered by each participant's own physicians, the registry also records urine organic acids.
Biomarkers & Outcomes
The T_rare Multi-Omic Tensor & Endpoints
Diagnostic Yield & VUS Reclassification
Proportion of previously unresolved cases achieving a definitive molecular diagnosis or pathogenic reclassification of Variants of Uncertain Significance (VUS) per ACMG guidelines.
Actionable Therapeutic Repurposing
Identification of targeted off-label small molecules, cofactor therapies, or metabolic bypass pathways under physician co-signature, turning intractable N=1 cases into treatable phenotypes.
Reduction in Diagnostic Burden
Quantifiable elimination of redundant invasive biopsies, exploratory surgeries, and uncoordinated subspecialty testing across the patient's care trajectory.
DeepSensi DCT
