时间标签：数据日期 2026-11-05 · 生成时间 2026-11-05 05:30（Asia/Shanghai）｜ 检索窗口 PubMed edat 2026/11/02 – 2026/11/06 ｜ 情报发生日期 2026-11-05
研究问题
Associations should be interpreted in the context of multiple testing and the exploratory design of the study.John Wiley & Sons, Ltd.3.5In Silico Functional Prediction Using CADDWe investigated the PHRED scale scores using CADD v1.6 software (Supporting Information: Table 5).；Although a train‐test split was applied for performance estimation, the primary objective was exploratory variant prioritization, not the validation of predictive models.
方法
Genes such as ACE2, TMPRSS2, SLC6A20, and elements of the HLA system in the reaction to the virus have drawn attention from whole‐exome sequencing and Genome‐Wide Association Studies (GWAS) [1].；Additionally, variations of innate immunity‐related genes, such as TLR7, TLR3, IRAK1, and OAS1‐3, have been linked to a higher risk of unfavorable outcomes [2].In Brazilian cohorts, various genetic analyses have identified specific variants and HLA alleles with potential influence on the antiviral immune response [3].；While there has been significant growth in the coronavirus disease 2019 (COVID‐19) genetic literature, research remains unevenly distributed, with heavy reliance on populations of European ancestry, and the majority of SARS‐related studies also involving East Asian participants [4].In this study, we applied a Support Vector Machine (SVM) framework to whole‐exome data from Brazilian individuals with confirmed COVID‐19.
核心结论
Figure 1 demonstrates the directional contribution of the 25 prioritized variants to the model predictions (SHAP).；Eight loci demonstrated significant genotype‐dependent expression differences in one or more tissues of interest for COVID‐19 (Supporting Information: Table 6).Expression‐associated signals were observed for PODN ‐ rs1769316 (lung), GAD2 ‐ rs2839671 (cerebellum), COL19A1 ‐ rs7762409 (cerebellum), NPC1 ‐ rs1367083 (lung, cardiovascular and brain regions), ODAD1 ‐ rs8107712 (whole blood and lung), NRP2 ‐ rs849526 (lung).；The TMEM11 ‐ rs3744223 variant also demonstrated moderate CADD scores, while the NPC1 ‐ rs1367083 variant showed widespread eQTL signals across lung and cardiovascular tissues in GTEx.
局限
Associations should be interpreted in the context of multiple testing and the exploratory design of the study.John Wiley & Sons, Ltd.3.5In Silico Functional Prediction Using CADDWe investigated the PHRED scale scores using CADD v1.6 software (Supporting Information: Table 5).；However, some variants presented moderately high scores, among which: NRP2 ‐ rs849526 (PHRED = 34), ITPR1 ‐ rs2306875 (PHRED = 20.7), ARRDC2 ‐ rs7259041 (PHRED = 18.15), RAI14 ‐ rs1048944 (PHRED = 16.40).；It is well recognized that clinical and demographic factors can influence the risk gradients observed in COVID‐19; however, they are not able to fully explain the observed interindividual variability.4.2Biological Characterization of Genes Prioritized by SHAPExploratory pathway enrichment analysis of the genes selected by SVM (n = 25) revealed processes related to mitochondria, neuroimmune signaling pathways, and complement activation.
对本项目的价值
中高价值：属「线粒体质量控制与氧化应激」方向；线粒体功能与氧化应激栏目可用作本项目文献库与综述素材。 ｜ 价值分 3.0/5（★★★☆☆）
全文来源
PubMed PMC JATS（正文 37,645 字符，题名指纹 0.77，已过 PubMed PMCID 官方关联 + 题名指纹 + 正文长度归属校验）
原文题录
- 中文题名：大规模巴西混合人群外显子组测序解析重症 COVID-19 宿主基因组通路图景
- 英文标题：Deciphering Host Genomic Pathway Landscapes in Severe COVID-19 by Exome Sequencing of a Large Admixed Brazilian Cohort.
- 期刊与标识：Journal of medical virology · PMID 42969658 · DOI 10.1002/jmv.71193 · PMC PMC13726577