High-throughput next generation sequencing has been successfully utilized in early screening, early diagnosis and real-time monitoring of tumor prognosis in precision medicine. Advancing case analysis and classification, course monitoring and medication guidance clinically. While manual operations in the process of library preparation and target enrichment for NGS can lead to deviations, MGI's automated sample preparation systems automate the labor-intensive and time-consuming procedures in diagnostic testing laboratories, to enhance the overall efficiency and reduce human errors in the laboratory.

MGI's MGISP-100 automated sample preparation system is an automated workstation specialized for high-throughput sequencing library preparation and nucleic acid extraction. It can process 16 samples per run and is suitable for small and medium-sized clinical laboratories. MGI's MGISP-960 high-throughput automated sample preparation system is a flexible, fully automated workstation with 96-channel pipette that is suitable for high-throughput and delivery-oriented laboratories. Both of MGI's MGISP automated sample preparation systems have obtained the qualification by the China National Medical Product Administration (NMPA). These integrated systems simplify the sample preparation procedure and enable a highly efficient streamlined workflow to reduce labor workload while improving the stability of library preparation (Fig. 1).

Fig. 1 MGISP automated library preparation system

To develop an integrated automation solution to empower tumor gene detection, MGI and Nanodigmbio, a biotechnology company specializing in molecular diagnostics and the technology of next generation sequencing, join forces to support the industry.

Evaluation plan

MGI and Nanodigmbio solution integrates MGI’s automated sample preparation systems; MGISP-100 and MGISP-960, and Nanodigmbio's NadPrep EZ DNA Library Preparation Kit (Fig. 2) and NanOnco Plus Panel v2.0 v2.0(~2.6 Mb) Targeted Capture Kit (Fig. 3), to complete the library preparation and targeted capture. Combining with DNBSEQ-G400*, it can provide an automated and efficient library preparation and sequencing solution for tumor gene detection.

Fig. 2. Nanodigmbio's NadPrep EZ DNA Library Preparation Kit for MGISP-100 and MGISP-960

Fig. 3. NanOnco Plus Panel v2.0 v2.0(~2.6 Mb) Targeted Capture Kit (Figure 3) for MGISP-100

Evaluation result

1. With Nanodigmbio's NadPrep EZ DNA Library Preparation Kit, MGISP automated library preparation systems have stable output, and the size distribution of all libraries show great uniformity and centrality.

Under experimental parameters, the output of automated libraries produced by the MGISP-100 and MGISP-960 was more than＞1000ng (Fig. 4). Although the number of samples has an influence on output, the output of different batches is stable. Furthermore, the distribution of all libraries based on the MGISP automated sample preparation systems met the preset standard (30min, ~250 bp insert DNA size) and show great uniformity and centrality among batches. There was no difference against manual operation (Fig. 5).

Fig. 4. NanOnco Plus Panel v2.0 v2.0(~2.6 Mb) Targeted Capture Kit (for MGI) has a stable output under Manual operation and on MGISP-100/960

Fig. 5. With NanOnco Plus Panel v2.0 v2.0(~2.6 Mb) Targeted Capture Kit (for MGI), the size distribution of all libraries shows great uniformity and centrality under Manual operation and on MGISP-100/960

2. Supported by NanOnco Plus Panel v2.0 (~2.6 Mb) for solid tumor analysis, MGISP automated sample preparation systems for library preparation showed highly consistent results.

Analysis carried out using the DNBSEQ-G400 sequencing platform* for PE100 with off-board data uniformly intercepted for 2M reads. Excellent indicators such as comparison rate > 99.8%, hit rate ~90% and 0.2× Mean >99% were obtained.  Hybridization capture was completed in 8 cycles using NanOnco Plus panel v2.0 and NadPre® hybridization capture reagent (Fig. 6).

Fig. 6. Sequencing performance of library preparation by manual and MGISP-100/960

3. Compared with manual library preparation, MGISP automated library preparation systems have higher SNP loci detection consistency.

SNP loci detection analysis can be used to identify the differences in mutation detection of different capture libraries methods. It was found that the correlation coefficients of SNP detection among batches of the same platform, different platforms, manual libraries, and ultrasonic fragmented libraries were all above 0.97, presenting high consistency (Fig. 7).

Fig. 7. The SNP loci in the library preparation by Manual/MG ISP-100/960 have good consistency.

Evaluation conclusion

MGI's MGISP automated library preparation systems combined with DNBSEQ-G400 genome sequencer* can accommodate various applications, throughput needs and budgets to empower tumor genetic detection. The MGISP-960 can process up to 96 samples per run and MGISP-100 can process 16 samples per run. Compared with manual library preparation, automated library preparation systems have the features of stable data performance, high efficiency and highly consistent library output. In addition, the MGISP sample preparation system is an open platform that is highly compatible with multiple third-party reagents to provide a high-quality automated library preparation system platform for tumor precision medicine.

*Unless otherwise informed, all sequencers and sequencing reagents are not available in Germany, USA, UK, Hong Kong, Sweden, Belgium, and Italy.