arXiv:2508.13552cs.LGcs.AI2025-08被引 6

新方法同时整合常见与罕见基因变异,提升疾病风险预测准确率。

Collapsing ROC approach for risk prediction research on both common and rare variants

  • 提出CROC方法,融合常见与罕见变异的预测模型构建
  • 在全部SNP下预测准确率AUC达0.605,优于仅用常见变异的0.585
  • 罕见变异为主时仍保持较高性能,适合全基因组风险研究

基于新兴遗传发现的风险预测对改善公共健康和临床诊疗具有重要意义。然而,现有基于常见遗传位点(如全基因组关联研究)的预测模型临床准确性不足。由于基因组中多数罕见变异尚未被纳入风险预测研究,未来应发展兼顾常见与罕见变异的综合策略。本文提出一种新的合并受试者工作特征(CROC)方法,是对先前前向受试者工作特征(FROC)方法的扩展,新增了处理罕见变异的流程。该方法在遗传分析工作坊17号迷你外显子数据集中的37个候选基因共533个单核苷酸多态性(SNPs)上进行评估。结果显示,包含所有SNPs的模型预测准确率(AUC=0.605)高于仅使用常见变异的模型(AUC=0.585)。通过逐步减少常见变异数量进一步验证,当常见变异减少时,CROC方法表现持续优于FROC方法。在极端情况下,仅存在罕见变异时,CROC达到AUC=0.603,而FROC仅为0.524。

原文摘要 · Abstract (English)

Risk prediction that capitalizes on emerging genetic findings holds great promise for improving public health and clinical care. However, recent risk prediction research has shown that predictive tests formed on existing common genetic loci, including those from genome-wide association studies, have lacked sufficient accuracy for clinical use. Because most rare variants on the genome have not yet been studied for their role in risk prediction, future disease prediction discoveries should shift toward a more comprehensive risk prediction strategy that takes into account both common and rare variants. We are proposing a collapsing receiver operating characteristic CROC approach for risk prediction research on both common and rare variants. The new approach is an extension of a previously developed forward ROC FROC approach, with additional procedures for handling rare variants. The approach was evaluated through the use of 533 single-nucleotide polymorphisms SNPs in 37 candidate genes from the Genetic Analysis Workshop 17 mini-exome data set. We found that a prediction model built on all SNPs gained more accuracy AUC = 0.605 than one built on common variants alone AUC = 0.585. We further evaluated the performance of two approaches by gradually reducing the number of common variants in the analysis. We found that the CROC method attained more accuracy than the FROC method when the number of common variants in the data decreased. In an extreme scenario, when there are only rare variants in the data, the CROC reached an AUC value of 0.603, whereas the FROC had an AUC value of 0.524.

风险预测基因变异统计方法遗传学

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