Department of Laboratory Medicine & Genetics, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon 51353, Republic of Korea.
Department of Laboratory Medicine, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan 31151, Republic of Korea.
Genes (Basel). 2023 Sep 26;14(10):1875. doi: 10.3390/genes14101875.
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 , , , , , , , and 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.
尽管基因组参考联盟人类构建 38 版（GRCh38）在改进方面优于 GRCh37，但它尚未被广泛采用。已经开发了几种基因座转换工具，作为实现 GRCh38 的便捷方法。本研究旨在调查基因座转换工具的准确性。从 ClinVar 下载了两个对齐到 GRCh37 和 GRCh38 的变体调用格式（VCF）文件（clinvar_20221217.vcf.gz）。使用 CrossMap、NCBI Remap 和 UCSC liftOver 等基因座转换工具将基因组坐标从 GRCh37 转换为 GRCh38。CrossMap、NCBI Remap 和 UCSC liftOver 的准确性分别为 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）。所有三种基因座转换工具都无法转换的变异均为插入/缺失/重复：一个致病性/可能致病性变异（n=1）和良性/可能良性变异（n=7）。无法转换的 8 个变异均位于 、 、 、 、 、 、 和 基因中，且所有变异均不在对齐到 GRCh37 的 VCF 文件中。本研究表明，三种基因座转换工具可成功将超过 99%的 ClinVar 变异的参考基因组从 GRCh37 转换为 GRCh38。本研究是首次使用基因座转换工具在临床上实施 GRCh38。需要进一步的临床研究来比较基因座转换工具的性能，并在常规临床环境中验证重新对齐方法。
