CAVaLRi: An Algorithm for Rapid Identification of Diagnostic Germline Variation

Figure 4

CAVaLRi demonstrates marked gains in diagnostic accuracy compared to existing methods in multiple patient cohorts. CAVaLRi was benchmarked against four leading diagnostic variant prioritization algorithms with clinician-curated phenotype sets (comparators include the hiPHIVE and PhenIX Exomiser prioritization, LIRICAL, and XRare). In the test partition for the clinical ES cohort, CAVaLRi displayed the highest accuracy as demonstrated by (a) higher PR AUC and (b) lower average diagnostic rank compared to all other algorithms. Similar relative performance was observed in the validation cohort (DDD) in terms of both (c) PR AUC and (d) average diagnostic rank.