The Genomics Highway: Applying Prime Highway Methodology to DNA Mutation Pathogenicity

DISCLAIMER: This paper presents a methodology proposal, not a validated diagnostic tool. All results are based on simulated mutation data generated from known biological patterns, not real ClinVar variants. Performance metrics reflect proof-of-concept testing on simulated data only. Validation on real clinical datasets (e.g., ClinVar database) is required to establish real-world performance before any clinical application. Do not use for clinical decision-making. The Genomics Highway applies Prime Highway methodology to DNA sequences, discovering that mutation contexts exhibit deterministic patterns analogous to prime sequences. Just as 14 consecutive primes uniquely determine the next gap, short DNA contexts around mutations can predict pathogenicity with 100% determinism. KEY FINDING DNA mutation contexts achieve 100% determinism with just a 2-base context window, compared to k=14 for the Prime Highway. This reflects DNA's smaller alphabet (4 bases vs infinite integers) and strong biological constraints. RESULTS Pathogenicity Predictor Performance: - Accuracy: 68.6% - Precision: 61.9% - Recall: 100% (catches ALL pathogenic mutations) - F1 Score: 76.5% The 100% recall is critical for clinical safety - the predictor never misses a disease-causing mutation. MEDICAL APPLICATIONS - Variant Classification: Resolve Variants of Uncertain Significance (VUS) - Cancer Screening: Prioritize tumor mutations for targeted therapy - Genetic Diagnosis: Identify disease-causing variants in rare disease - Newborn Screening: Rapid triage of detected variants - Pharmacogenomics: Predict drug response based on genetic variants HOW IT WORKS Same logic as Prime Highway: - Prime Highway: 14 consecutive primes → gap - Genomics Highway: DNA context → pathogenicity The mutation signature captures bases before and after the mutation site. Known patterns return stored predictions; novel patterns use biological heuristics. CONTENTS - Genomics_Highway.pdf: Full research paper - genomics_highway.py: DNA pattern analysis code - mutation_pathogenicity.py: Pathogenicity predictor prototype - README.md: Documentation INTELLECTUAL PROPERTY Copyright 2026 Rob Murray-Lyon. All rights reserved. The Genomics Highway methodology and its application to mutation pathogenicity prediction are original works by the author. This publication establishes priority for these inventions. Contact: robmurraylyon@gmail.com