Benchmarking of human Y-chromosomal haplogroup classifiers with whole-genome and whole-exome sequence data

• Published in: Computational and structural biotechnology journal Vol. 21; pp. 4613 - 4618
• Main Authors: García-Olivares, Víctor, Muñoz-Barrera, Adrián, Rubio-Rodríguez, Luis A., Jáspez, David, Díaz-de Usera, Ana, Iñigo-Campos, Antonio, Veeramah, Krishna R., Alonso, Santos, Thomas, Mark G., Lorenzo-Salazar, José M., González-Montelongo, Rafaela, Flores, Carlos
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.01.2023; Research Network of Computational and Structural Biotechnology; Elsevier
• Subjects: biotechnology; Comparative genomics; data collection; forensic sciences; genome; humans; Next-generation sequencing; NRY haplogroup classification; pedigree; Population genetics; Y chromosome; Comparative genomics; NRY haplogroup classification; Next-generation sequencing; Population genetics; Y chromosome
• ISSN: 2001-0370; 2001-0370
• DOI: 10.1016/j.csbj.2023.09.012

In anthropological, medical, and forensic studies, the nonrecombinant region of the human Y chromosome (NRY) enables accurate reconstruction of pedigree relationships and retrieval of ancestral information. Using high-throughput sequencing (HTS) data, we present a benchmarking analysis of command-line tools for NRY haplogroup classification. The evaluation was performed using paired Illumina data from whole-genome sequencing (WGS) and whole-exome sequencing (WES) experiments from 50 unrelated donors. Additionally, as a validation, we also used paired WGS/WES datasets of 54 individuals from the 1000 Genomes Project. Finally, we evaluated the tools on data from third-generation HTS obtained from a subset of donors and one reference sample. Our results show that WES, despite typically offering less genealogical resolution than WGS, is an effective method for determining the NRY haplogroup. Y-LineageTracker and Yleaf showed the highest accuracy for WGS data, classifying precisely 98% and 96% of the samples, respectively. Yleaf outperforms all benchmarked tools in the WES data, classifying approximately 90% of the samples. Yleaf, Y-LineageTracker, and pathPhynder can correctly classify most samples (88%) sequenced with third-generation HTS. As a result, Yleaf provides the best performance for applications that use WGS and WES. Overall, our study offers researchers with a guide that allows them to select the most appropriate tool to analyze the NRY region using both second- and third-generation HTS data. [Display omitted] •Whole-exome sequencing provides sufficient information to classify the NRY haplogroup.•Among the tools evaluated, YLeaf offers the best performance.•Nanopore sequencing technology provides enough resolution to accurately retrieve NRY haplogroup.