The importance of structural variants(SVs)for human phenotypes and diseases is now recognized.Although a variety of SV detection platforms and strategies that vary in sensitivity and specificity have been developed,few benchmarking procedures are available to confidently assess their performances in biological and clinical research.To facilitate the validation and application of these SV detection approaches,we established an Asian reference material by characterizing the genome of an Epstein-Barr virus(EBV)-immortalized B lymphocyte line along with identified benchmark regions and high-confidence SV calls.We established a high-confidence SV callset with 8938 SVs by integrating four alignment-based SV callers,including 109x Pacific Biosciences(PacBio)continuous long reads(CLRs),22 x PacBio circular consensus sequencing(CCS)reads,104x Oxford Nanopore Technologies(ONT)long reads,and 114×Bionano optical mapping plat-form,and one de novo assembly-based SV caller using CCS reads.A total of 544 randomly selected SVs were validated by PCR amplification and Sanger sequencing,demonstrating the robustness of our SV calls.Combining trio-binning-based haplotype assemblies,we established an SV benchmark for identifying false negatives and false positives by constructing the continuous high-confidence regions(CHCRs),which covered 1.46 gigabase pairs(Gb)and 6882 SVs supported by at least one diploid haplotype assembly.Establishing high-confidence SV calls for a benchmark sample that has been characterized by multiple technologies provides a valuable resource for investigating SVs in human biology,disease,and clinical research.

Xiao Du;Lili Li;Fan Liang;Sanyang Liu;Wenxin Zhang;Shuai Sun;Yuhui Sun;Fei Fan;Linying Wang;Xinming Liang;Weijin Qiu;Guangyi Fan;Ou Wang;Weifei Yang;Jiezhong Zhang;Yuhui Xiao;Yang Wang;Depeng Wang;Shoufang Qu;Fang Chen;Jie Huang

BGI-Qingdao,BGI-Shenzhen,Qingdao 266555,China;State Key Laboratory of Agricultural Genomics,BGI-Shenzhen,Shenzhen 518083,China;National Institutes for food and drug Control(NIFDC),Beijing 10050,China;GrandOmics Biosciences,Beijing 102200,China;Annoroad Gene Technology(Beijing)Co.,Ltd.,Beijing 102200,China;China National Gene Bank,BGI-Shenzhen,Shenzhen 518120,China;BGI-Shenzhen,Shenzhen 518083,China;MGI,BGI-Shenzhen,Shenzhen 518083,China

基因组蛋白质组与生物信息学报（英文版）

[1]Xiao Du;Lili Li;Fan Liang;Sanyang Liu;Wenxin Zhang;Shuai Sun;Yuhui Sun;Fei Fan;Linying Wang;Xinming Liang;Weijin Qiu;Guangyi Fan;Ou Wang;Weifei Yang;Jiezhong Zhang;Yuhui Xiao;Yang Wang;Depeng Wang;Shoufang Qu;Fang Chen;Jie Huang-.Robust Benchmark Structural Variant Calls of An Asian Using State-of-the-art Long-read Sequencing Technologies)[J].基因组蛋白质组与生物信息学报（英文版）,2022(01):192-204

callset,callers,109x,Bionano,caller,CHCRs,gigabase

Robust,Benchmark,Structural,Variant,Calls,An,Asian,Using,State,art,Long,Sequencing,Technologies,importance,structural,variants,SVs,human,phenotypes,diseases,now,recognized,Although,variety,detection,platforms,strategies,that,vary,sensitivity,specificity,have,been,developed,few,benchmarking,procedures,are,available,confidently,assess,their,performances,biological,clinical,research,To,facilitate,validation,application,these,approaches,established,reference,material,by,characterizing,genome,Epstein,Barr,virus,EBV,immortalized,lymphocyte,line,along,identified,regions,high,confidence,We,integrating,four,alignment,including,Pacific,Biosciences,PacBio,continuous,reads,CLRs,circular,consensus,sequencing,CCS,104x,Oxford,Nanopore,ONT,optical,mapping,one,novo,assembly,using,total,randomly,selected,were,validated,amplification,Sanger,demonstrating,robustness,Combining,trio,binning,haplotype,assemblies,identifying,false,negatives,positives,constructing,which,covered,pairs,Gb,supported,least,diploid,Establishing,sample,has,characterized,multiple,technologies,provides,valuable,resource,investigating,biology

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