Fig. 2 | Nature Communications

Fig. 2

From: Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP

Fig. 2

Diagnostically discriminative VEP-G2P disease-specific output. VEP-G2P analysis of three independent WES cohorts; DDD (n = 7357), CRC (n = 517) and GS (n = 315). a Odds ratios for samples carrying at least one valid G2P variant (passing the G2P criteria and on a canonical transcript) in 454 unique G2PDD monoallelic genes: DDD vs GS (red) and CRC vs GS (black); two-tail Fisher’s Exact Test: *p-value ≤ 5 × 10-2, **p-value ≤ 5 × 10-3, ***p-value ≤ 5 × 10-6, n.s not significant; considering only missense variants where SIFT and PolyPhen agree deleterious/damaging. b Odds ratios for samples carrying at least one valid G2P variant in 950 different G2PDD biallelic genes. No stop_lost and inframe_insertion variants were found in the GS cohort and few in DDD or CRC (p-value > 5 × 10−2). Error bars = 95% confidence intervals (CI) in a and b. c Proportion of individuals in the three cohorts (y-axis) carrying a particular number of LOF and missense (regardless of their SIFT/PolyPhen status and CADD score) variants reported by VEP-G2PDD (x-axis). The proportion of DDD individuals for which no VEP-G2PDD hit is found is significantly lower compared to CRC and GS cohorts, both for monoallelic (p-values for two-tail Fisher’s Exact Test comparing number of individuals for which no variants is found to those for which at least one variant is found: DDD vs GS = 7.9e-09, DDD vs CRC = 2.3e-12, CRC vs GS = 0.93) and biallelic genes (DDD vs GS = 1.5e-10, DDD vs CRC = 1.5e-11, CRC vs GS = 0.39). DDD (n = 7357 individuals), CRC (n = 517), GS (n = 315). d DDD cohort is significantly enriched for unique missense variants with CADD > 30 in G2PDD genes (top) compared to GS (p-value two-tail Fisher’s Exact Test = 0.005); with no significant difference between DDD and CRC (p-value = 0.17) and CRC and GS (p-value = 0.16). There is no significant difference for the proportion of unique missense variants with CADD > 30 in the CRC and GS cohorts in G2PCancer genes (bottom, p-value = 1.0)

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