尽管基因组参考联盟HumanBuild38(GRCh38)的发布比GRCh37有所改进,但尚未被广泛采用。已经开发了几种liftover工具,作为GRCh38实施的便捷方法。本研究旨在探讨基因组转换的生命周期工具的准确性。从ClinVar(clinvar_20221217下载了与GRCh37和GRCh38对齐的两个变体调用格式(VCF)文件。vcf.gz).提升工具,如CrossMap,NCBI重映射,和UCSCliftOver用于将基因组坐标从GRCh37转换为GRCh38。CrossMap的准确性,NCBI重映射,UCSC提升率为99.81%(1,567,838/1,570,748),99.69%(1,565,953/1,570,748),和99.99%(1,570,550/1,570,748),分别。通过所有三个提升工具未能转化的变体都是插入缺失/重复:致病性/可能致病性变体(n=1)和良性/可能良性变体(n=7)。在ALMS中识别出了八种无法转换的变体,TTN,CFTR,SLCO,LDLR,PCNT,MID1和GRIA3基因,并且所有变体都不在与GRCh37对齐的VCF文件中。这项研究表明,在超过99%的ClinVar变体中,三种提升工具可以成功地将GRCh37的参考基因组转换为GRCh38。这项研究采取的第一步,临床实施GRCh38使用提升工具。有必要进行进一步的临床研究,以比较提升工具的性能,并在常规临床环境中验证重新对齐方法。
Although Genome Reference Consortium Human Build 38 (GRCh38) was released with improvement over GRCh37, it has not been widely adopted. Several liftover tools have been developed as a convenient approach for GRCh38 implementation. This study aimed to investigate the accuracy of liftover tools for genome conversion. Two Variant Call Format (VCF) files aligned to GRCh37 and GRCh38 were downloaded from
ClinVar (clinvar_20221217.vcf.gz). Liftover tools such as CrossMap, NCBI Remap, and UCSC liftOver were used to convert genome coordinates from GRCh37 to GRCh38. The accuracy of CrossMap, NCBI Remap, and UCSC liftOver were 99.81% (1,567,838/1,570,748), 99.69% (1,565,953/1,570,748), and 99.99% (1,570,550/1,570,748), respectively. Variants that failed conversion via all three liftover tools were all indels/duplications: a pathogenic/likely pathogenic variant (n = 1) and benign/likely benign variants (n = 7). The eight variants that failed conversion were identified in the ALMS, TTN, CFTR, SLCO, LDLR, PCNT, MID1, and GRIA3 genes, and all the variants were not in the VCF files aligned to GRCh37. This study demonstrated that three liftover tools could successfully convert reference genomes from GRCh37 to GRCh38 in more than 99% of
ClinVar variants. This study takes the first step to clinically implement GRCh38 using liftover tools. Further clinical studies are warranted to compare the performance of liftover tools and to validate re-alignment approaches in routine clinical settings.