Material Measurement Laboratory, National Institute of Standards and Technology, Gaithersburg, MD, USA.
UC Santa Cruz Genomics Institute, University of California Santa Cruz, Santa Cruz, CA, USA.
Nat Rev Genet. 2023 Jul;24(7):464-483. doi: 10.1038/s41576-023-00590-0. Epub 2023 Apr 14.
Genetic variant calling from DNA sequencing has enabled understanding of germline variation in hundreds of thousands of humans. Sequencing technologies and variant-calling methods have advanced rapidly, routinely providing reliable variant calls in most of the human genome. We describe how advances in long reads, deep learning, de novo assembly and pangenomes have expanded access to variant calls in increasingly challenging, repetitive genomic regions, including medically relevant regions, and how new benchmark sets and benchmarking methods illuminate their strengths and limitations. Finally, we explore the possible future of more complete characterization of human genome variation in light of the recent completion of a telomere-to-telomere human genome reference assembly and human pangenomes, and we consider the innovations needed to benchmark their newly accessible repetitive regions and complex variants.
从 DNA 测序中进行遗传变异调用，使我们能够理解数以十万计的人类的种系变异。测序技术和变异调用方法迅速发展，通常可在人类基因组的大部分区域提供可靠的变异调用结果。我们描述了长读长、深度学习、从头组装和泛基因组如何扩展了对包括医学相关区域在内的日益具有挑战性和重复性的基因组区域的变异调用的访问权限，以及新的基准集和基准测试方法如何揭示它们的优缺点。最后，我们考虑了在最近完成端粒到端粒人类基因组参考组装和人类泛基因组之后，更全面地描述人类基因组变异的可能的未来，并考虑了对其新可及的重复区域和复杂变异进行基准测试所需的创新。
