Background: BGISEQ-500 is a new desktop sequencer developed by BGI. Using DNA nanoball and combinational probe anchor synthesis developed from Complete Genomics™ sequencing technologies, it generates short reads at a large scale. Findings: Here, we present the first human whole-genome sequencing dataset of BGISEQ-500. The dataset was generated by sequencing the widely used cell line HG001 (NA12878) in two sequencing runs of paired-end 50 bp (PE50) and two sequencing runs of paired-end 100 bp (PE100). We also include examples of the raw images from the sequencer for reference. Finally, we identified variations using this dataset, estimated the accuracy of the variations, and compared to that of the variations identified from similar amounts of publicly available HiSeq2500 data. Conclusions: We found similar single nucleotide polymorphism (SNP) detection accuracy for the BGISEQ-500 PE100 data (false positive rate [FPR] = 0.00020%, sensitivity = 96.20%) compared to the PE150 HiSeq2500 data (FPR = 0.00017%, sensitivity = 96.60%) better SNP detection accuracy than the PE50 data (FPR = 0.0006%, sensitivity = 94.15%). But for insertions and deletions (indels), we found lower accuracy for BGISEQ-500 data (FPR = 0.00069% and 0.00067% for PE100 and PE50 respectively, sensitivity = 88.52% and 70.93%) than the HiSeq2500 data (FPR = 0.00032%, sensitivity = 96.28%). Our dataset can serve as the reference dataset, providing basic information not just for future development, but also for all research and applications based on the new sequencing platform.

Background: DNBSEQ™ platforms are new massively parallel sequencing (MPS) platforms that use DNA nanoball technology. Use of data generated from DNBSEQ™ platforms to detect single nucleotide variants (SNVs) and small insertions and deletions (indels) has proven to be quite effective, while the feasibility of copy number variants (CNVs) detection is unclear. Results: Here, we first benchmarked different CNV detection tools based on Illumina whole-genome sequencing (WGS) data of NA12878 and then assessed these tools in CNV detection based on DNBSEQ™ sequencing data from the same sample. When the same tool was used, the CNVs detected based on DNBSEQ™ and Illumina data were similar in quantity, length and distribution, while great differences existed within results from different tools and even based on data from a single platform. We further estimated the CNV detection power based on available CNV benchmarks of NA12878 and found similar precision and sensitivity between the DNBSEQ™ and Illumina platforms. We also found higher precision of CNVs shorter than 1 kbp based on DNBSEQ™ platforms than those based on Illumina platforms by using Pindel, DELLY and LUMPY. We carefully compared these two available benchmarks and found a large proportion of specific CNVs between them. Thus, we constructed a more complete CNV benchmark of NA12878 containing 3512 CNV regions. Conclusions: We assessed and benchmarked CNV detections based on WGS with DNBSEQ™ platforms and provide guidelines for future studies.

We found several inaccurate descriptions in our recently published paper, “A reference human genome dataset of the BGISEQ-500 sequencer” [1], thus we would like to make the following corrections.

Ring chromosome 18 [r(18)] is formed by 18p- and 18q- partial deletion and generates a ring chromosome. Loss of critical genes on each arm of chromosome 18 may contribute to the specific phenotype, and the clinical spectrum varieties may heavily depend on the extent of the genomic deletion. The aim of this study is to identify the detailed breakpoints location and the deleted genes result from the r18. Here we describe a detailed diagnosis of a seven-year-old Chinese girl with a ring chromosome 18 mutation by a high-throughput whole-genome low-coverage sequencing approach without karyotyping and other cytogenetic analysis. This method revealed two fragment heterozygous deletions of 18p and 18q, and further localized the detailed breakpoint sites and fusion, as well as the deleted genes. To our knowledge, this is the first report of a ring chromosome 18 patient in China analyzed by whole-genome low-coverage sequencing approach. Detailed breakpoints location and deleted genes identification help to estimate the risk of the disease in the future. The data and analysis here demonstrated the feasibility of next-generation sequencing technologies for chromosome structure variation including ring chromosome in an efficient and cost effective way.

Objective: To evaluate the clinical validity of a new ultrahigh‐throughput non‐invasive prenatal test (NIPT) based on combinatorial probe–anchor ligation (cPAL) sequencing of cell‐free fetal DNA (cffDNA) using centralized testing.Methods: Maternal plasma samples were obtained from 10 594 singleton pregnancies in high‐risk populations at 20 centers in China, including 8155 that were collected retrospectively and 2439 prospectively. Fetal outcome data and karyotyping results were documented as gold standard and were double blinded during NIPT. The clinical performance of the ultrahigh‐throughput sequencing method, cPAL, for NIPT was validated by evaluating its sensitivity, specificity and positive predictive value (PPV) in detecting trisomies 21, 18 and 13 as the centralized testing mode in the reference laboratory. To ensure stable and reproducible performance of centralized cPAL‐based NIPT in detecting trisomies, a series of quality‐control systems, including sequencing of two sets of artificial samples, were employed and evaluated.Results: Ten prospective cases were excluded from the study because of incomplete clinical data. Four prospective samples failed to generate a NIPT result due to assay failure, presenting a failure rate of 0.16% (4/2429). A total of 168 retrospective cases and 47 prospective cases had a positive NIPT result for trisomy, giving respective positive rates of 2.06% and 1.94%. Four false‐positive and no false‐positive cases were observed in the retrospective and prospective groups, respectively, resulting in PPV of 97.62% (95% CI, 94.02–99.35%) and 100% (95% CI, 92.45–100%), respectively. In the retrospective group, sensitivity and specificity were, respectively, 100% (95% CI, 97.07–100%) and 99.98% (95% CI, 99.94–100%) for trisomy 21, 100% (95% CI, 97.75–100%) and 99.98% (95% CI, 99.94–100%) for trisomy 18, and 100% (95% CI, 15.81–100%) and 100% (95% CI, 99.95–100%) for trisomy 13. In the prospective group, sensitivity and specificity were, respectively, 100% (95% CI, 90.75–100%) and 100% (95% CI, 99.85–100%) for trisomy 21, 100% (95% CI, 63.06–100%) and 100% (95% CI, 99.85–100%) for trisomy 18, and 100% (95% CI, 2.50–100%) and 100% (95% CI, 99.85–100%) for trisomy 13.Conclusion: In this multicenter study with a full quality‐control system, NIPT by centralized cPAL‐based testing showed high stability and performance comparable to those of previous validation studies in high‐risk populations. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.