基因分型
校准
概率逻辑
软件
计算生物学
计算机科学
统计
生物
人工智能
遗传学
数学
基因型
基因
程序设计语言
作者
Moya McCarthy-Allen,Øyvind Bleka,Rolf J. F. Ypma,Peter Gill,Corina C.G. Benschop
标识
DOI:10.1101/2024.06.06.597689
摘要
Abstract The validity of a probabilistic genotyping (PG) system is typically demonstrated by following international guidelines for the developmental and internal validation of PG software. These guidelines mainly focus on discriminatory power. Very few studies have reported with metrics that depend on calibration of likelihood ratio (LR) systems. In this study, discriminatory power as well as various calibration metrics, such as Empirical Cross-Entropy (ECE) plots, pool adjacent violator (PAV) plots, log likelihood ratio cost (Cllr and Cllr cal ), fiducial calibration discrepancy plots, and Turing’ expectation were examined using the publicly-available PROVEDIt dataset. The aim was to gain deeper insight into the performance of a variety of PG software in the ‘lower’ LR ranges (∼LR 1-10,000), with focus on DNAStatistX and EuroForMix which use maximum likelihood estimation (MLE). This may be a driving force for the end users to reconsider current LR thresholds for reporting. In previous studies, overstated ‘low’ LRs were observed for these PG software. However, applying (arbitrarily) high LR thresholds for reporting wastes relevant evidential value. This study demonstrates, based on calibration performance, that previously reported LR thresholds can be lowered or even discarded. Considering LRs >1, there was no evidence for miscalibration performance above LR ∼1,000 when using Fst 0.01. Below this LR value, miscalibration was observed. Calibration performance generally improved with the use of Fst 0.03, but the extent of this was dependent on the dataset: results ranged from miscalibration up to LR ∼100 to no evidence of miscalibration alike PG software using different methods to model peak height, HMC and STRmix. This study demonstrates that practitioners using MLE-based models should be careful when low LR ranges are reported, though applying arbitrarily high LR thresholds is discouraged. This study also highlights various calibration metrics that are useful in understanding the performance of a PG system. Highlights Discriminatory power and calibration performance of PG software are evaluated. The utility of various calibration metrics are explored in ‘low’ LR ranges. Focus was on DNAStatistX and EuroForMix software using the MLE method. Calibration performance was dependent on Fst value and dataset size. Results suggest reconsideration of lower LR thresholds and cautious reporting of ‘low’ LRs.
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