Simultaneous estimation of genotype error and uncalled deletion rates in whole genome sequence data.

Genotype data include errors that may influence conclusions reached by downstream statistical analyses. Previous studies have estimated genotype error rates from discrepancies in human pedigree data, such as Mendelian inconsistent genotypes or apparent phase violations. However, uncalled deletions, which generally have not been accounted for in these studies, can lead to biased error rate estimates. In this study, we propose a genotype error model that considers both genotype errors and uncalled deletions when calculating the likelihood of the observed genotypes in parent-offspring trios. Using simulations, we show that when there are uncalled deletions, our model produces genotype error rate estimates that are less biased than estimates from a model that does not account for these deletions. We applied our model to SNVs in 77 sequenced White British parent-offspring trios in the UK Biobank. We use the Akaike information criterion to show that our model fits the data better than a model that does not account for uncalled deletions. We estimate the genotype error rate at SNVs with minor allele frequency > 0.001 in these data to be [Formula: see text]. We estimate that 77% of the genotype errors at these markers are attributable to uncalled deletions [Formula: see text].

Multicenter Validation of Abbreviated MRI for Detecting Early-Stage Hepatocellular Carcinoma.

Background Abbreviated MRI is a proposed paradigm shift for hepatocellular carcinoma (HCC) surveillance, but data on its performance are lacking for histopathologically confirmed early-stage HCC. Purpose To evaluate the sensitivity and specificity of dynamic contrast-enhanced abbreviated MRI for early-stage HCC detection, using surgical pathologic findings as the reference standard. Materials and Methods This retrospective study was conducted at three U.S. liver transplant centers in patients with cirrhosis who underwent liver resection or transplant between January 2009 and December 2019 and standard "full" liver MRI with and without contrast enhancement within 3 months before surgery. Patients who had HCC-directed treatment before surgery were excluded. Dynamic abbreviated MRI examinations were simulated from the presurgical full MRI by selecting the coronal T2-weighted and axial three-dimensional fat-suppressed T1-weighted dynamic contrast-enhanced sequences at precontrast, late arterial, portal venous, and delayed phases. Two abdominal radiologists at each center independently interpreted the simulated abbreviated examinations with use of the Liver Imaging Reporting and Data System version 2018. Patients with any high-risk liver observations (>LR-3) were classified as positive; otherwise, they were classified as negative. With liver pathologic findings as the reference standard for the presence versus absence of early-stage HCC, the sensitivity, specificity, and their 95% CIs were calculated. Logistic regression was used to identify factors associated with correct classification. Results A total of 161 patients with early-stage HCC (median age, 62 years [IQR, 58-67 years]; 123 men) and 138 patients without HCC (median age, 55 years [IQR, 47-63 years]; 85 men) were confirmed with surgical pathologic findings. The sensitivity and specificity of abbreviated MRI were 88.2% (142 of 161 patients) (95% CI: 83.5, 92.5) and 89.1% (123 of 138 patients) (95% CI: 84.4, 93.8), respectively. Sensitivity was lower for Child-Pugh class B or C versus Child-Pugh class A cirrhosis (64.1% vs 94.2%; P < .001). Conclusion With surgical pathologic findings as the reference standard, dynamic abbreviated MRI had high sensitivity and specificity for early-stage hepatocellular carcinoma detection in patients with compensated cirrhosis but lower sensitivity in those with decompensated cirrhosis. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Kim in this issue.