IW-Scoring: an Integrative Weighted Scoring framework for annotating and prioritizing genetic variations in the noncoding genome

IW-Scoring represents a new Integrative Weighted Scoring model to annotate and prioritise functionally relevant noncoding variations. The pipeline integrates 11 popular algorithms and outperforms individual methods in three independent data sets, including variants in ClinVar database and GWAS studies, and cancer mutations. Using IW-Scoring, we located 11 recurrently mutated noncoding regions enriched for at least three functional mutations in 14 follicular lymphoma genomes, and validated 9 clusters (82%) in the International Cancer Genome Consortium cohort (n=36), including promoter and enhancer regions of PAX5. IW-Scoring offers greater versatility to identify trait and disease associated noncoding variants.