We describe IW-Scoring, a new integrative weighted scoring framework to annotate and prioritize noncoding variations.
IW-Scoring consists of four top-level modules, including gene annotation, regulatory annotation, functional scoring, and score integration and significance inference.
IW-Scoring contains separate workflows for scoring known and novel variants.
For known variants, we provide two IW-scores with the associated p-values: one that aggregates scores from 11
functional scoring systems including fitCons, and the other excluding fitCons. This approach is useful for ranking and narrowing down variants
indicated in GWAS and QTL studies, as well as rare known variants in hereditary diseases. As GWAVA only scores known variants, the workflow for novel variants
excludes GWAVA scores from the aggregate calculation and provides two integrative scores: one that aggregates scores from the other eight scoring systems, and
the other further excluding CADD and DeepSEA scores. This workflow is preferred for variants identified in cancer and other somatic diseases. In situations where
users do not know which options to choose, they can use both workflows to generate IW-scores. The percentage of queried variants that are scored by GWAVA can further
guide users in interpreting which IW-scores would be more reliable.