As a result of the COVID-19 outbreak, the 53rd European Congress of Human Genetics (ESHG 2020) was held online this year. MGI CSO Dr Rade Drmanac, Dr Nik Matthews of the Institute of Cancer Research (UK), Prof Miguel Esteban of the Chinese Academy of Sciences Guangzhou Institute of Biomedicine and Health, and Prof Lars Engstrand of the Karolinska Institute and Science for Life Laboratory in Sweden shared the latest developments in high-throughput sequencing technologies, as well as their experiences supporting scientific research during the global fight against COVID-19.
Among the speakers, Prof Lars Engstrand presented his team’s work in Sweden and their experience supporting COVID-19 testing and research.
“We started collaboration with MGI at the beginning of April and the lab was established a couple of weeks ago. In the last four weeks, we turned our microbiome lab into a high-throughput COVID-19 testing lab in Stockholm. It is urgent to increase testing capacity. We need this not only for diagnosing infected individuals but also for epidemiology and tracking mutations.”
— Prof Lars Engstrand
Centre for Translational Microbiome Research and the Fight against COVID-19
In response to the impact of COVID-19, Sweden urgently needed to increase its testing capacity. In late March 2020, a laboratory capable of processing 10,000 COVID-19 tests per day was jointly established with MGI at the Centre for Translational Microbiome Research (CTMR) at the Karolinska Institute. The facility supports epidemiological monitoring and follow-up studies. CTMR also serves as Sweden’s National Pandemic Center.
In addition to RT-PCR testing at CTMR, high-throughput sequencing platforms DNBSEQ-G400 and the ultra-high-throughput DNBSEQ-T7 were deployed for novel coronavirus sequencing. These platforms enable more comprehensive and timely mapping of viral spread and mutation detection.
Over 10,000 samples per day: the importance of high-throughput automation
Faced with the need for large-scale RT-PCR testing, high-throughput automated viral nucleic acid extraction systems significantly reduce manual work while increasing processing speed. CTMR is currently equipped with ten MGISP-960 systems, which theoretically support testing capacity of up to 10,000 samples per day.
To address the need for large-scale viral genome sequencing, the DNBSEQ-T7 and DNBSEQ-G400 platforms were used with two sequencing approaches: shotgun metagenomic sequencing and multiplex PCR sequencing (ATOPlex). These methods enable further analysis of samples, including genome assembly, sequencing coverage and depth analysis, and SNV detection.
Metagenomic sequencing or multiplex PCR sequencing (ATOPlex)
Metagenomic sequencing captures both host and microbiome sequences and can detect unknown pathogens and potential co-infections. Multiplex PCR sequencing focuses on the target virus, enabling full-length viral genome reconstruction from limited sequencing data.
During the initial study phase, both sequencing approaches were tested on the DNBSEQ-G400 platform. The results were consistent, with both methods detecting SNP variations as well as an 18 bp deletion. These findings demonstrate that both approaches can effectively monitor viral evolution and mutation.
DNBSEQ-T7 or DNBSEQ-G400
In this study, metagenomic sequencing of COVID-19 samples was performed on both the DNBSEQ-T7 and DNBSEQ-G400 platforms. Although sequencing depth differed, results from the same samples were highly consistent across both systems, demonstrating strong concordance between DNBSEQ sequencing platforms.
For large-scale projects, the ultra-high-throughput DNBSEQ-T7 can process up to 128 metagenomic sequencing samples (PE100, 100M reads per sample) or 3,840 multiplex PCR samples (ATOPlex, 5M reads per sample) in a single run. For smaller studies, the DNBSEQ-G400 offers a lower cost per run. Ultimately, the choice of platform depends on the daily sample volume.
Multi-omics research on COVID-19
Scientists around the world are actively conducting research and testing related to COVID-19. Multi-omics research includes studies of the host genome, metagenomics, viral genomics, single-cell analysis, and proteomics. These research areas will remain a key focus for CTMR in the near future.
At the same time, efforts are underway to validate the feasibility of large-scale COVID-19 testing and screening in Sweden. High-throughput sequencing technologies and multi-omics approaches are expected to play an essential role in the global fight against COVID-19.
