Quartet DNA reference materials and datasets for comprehensively evaluating germline variant calling performance

Luyao Ren, Xiaoke Duan, Lianhua Dong, Rui Zhang, Jingcheng Yang, Yuechen Gao, Rongxue Peng, Wanwan Hou, Yaqing Liu, Jingjing Li, Ying Yu, Naixin Zhang, Jun Shang, Fan Liang, Depeng Wang, Hui Chen, Lele Sun, Lingtong Hao, Andreas Scherer, Jessica NordlundWenming Xiao, Joshua Xu, Weida Tong, Xin Hu, Peng Jia, Kai Ye, Jinming Li, Li Jin, Huixiao Hong, Jing Wang, Shaohua Fan, Xiang Fang, Yuanting Zheng, Leming Shi

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review


Background: Genomic DNA reference materials are widely recognized as essential for ensuring data quality in omics research. However, relying solely on reference datasets to evaluate the accuracy of variant calling results is incomplete, as they are limited to benchmark regions. Therefore, it is important to develop DNA reference materials that enable the assessment of variant detection performance across the entire genome. Results: We established a DNA reference material suite from four immortalized cell lines derived from a family of parents and monozygotic twins. Comprehensive reference datasets of 4.2 million small variants and 15,000 structural variants were integrated and certified for evaluating the reliability of germline variant calls inside the benchmark regions. Importantly, the genetic built-in-truth of the Quartet family design enables estimation of the precision of variant calls outside the benchmark regions. Using the Quartet reference materials along with study samples, batch effects are objectively monitored and alleviated by training a machine learning model with the Quartet reference datasets to remove potential artifact calls. Moreover, the matched RNA and protein reference materials and datasets from the Quartet project enables cross-omics validation of variant calls from multiomics data. Conclusions: The Quartet DNA reference materials and reference datasets provide a unique resource for objectively assessing the quality of germline variant calls throughout the whole-genome regions and improving the reliability of large-scale genomic profiling.

TidskriftGenome Biology
Antal sidor31
StatusPublicerad - dec. 2023
MoE-publikationstypA1 Tidskriftsartikel-refererad

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© 2023, The Author(s).


  • 1184 Genetik, utvecklingsbiologi, fysiologi

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