DNBSEQ technology, developed by MGI (a BGI Group subsidiary), is a high-throughput, next-generation sequencing method. It enables researchers and clinicians to gain insights with greater precision and efficiency. This technology is impactful in large-scale genomic studies, providing comprehensive data for scientific and medical applications.
Understanding DNBSEQ Technology
DNBSEQ technology operates on the principles of DNA Nanoballs (DNBs) and Combinatorial Probe-Anchor Synthesis (cPAS). The process begins by preparing DNA fragments: double-stranded DNA is denatured into single strands. Adapter sequences are added, and these strands are circularized using a splint oligonucleotide and DNA ligase, forming stable single-stranded circular templates.
These circular DNA templates undergo rolling circle replication (RCR) to produce numerous copies. These amplified copies concatenate into long strands, which condense into compact DNA Nanoballs (DNBs). DNBs are then loaded onto a patterned array flow cell, designed with uniformly spaced binding sites, ensuring each site binds a single DNB.
Sequencing proceeds with cPAS chemistry. A sequencing primer hybridizes to an adapter region on the DNB. Fluorescently labeled dNTP probes, corresponding to specific DNA bases, are incorporated by a DNA polymerase in cycles. After each incorporation, unbound probes are washed away, and the flow cell is imaged to capture fluorescence signals. Proprietary algorithms analyze these images to accurately determine the DNA sequence for each DNB.
Applications in Research and Healthcare
DNBSEQ technology is widely applied across various research and healthcare domains. In genomics, it facilitates whole genome sequencing (WGS), allowing for comprehensive analysis of an organism’s entire genetic makeup. This capability extends to exome sequencing, focusing on the protein-coding regions of the genome.
The technology also supports RNA sequencing for insights into gene expression patterns, and epigenetics studies, examining DNA modifications that influence gene activity. DNBSEQ is utilized in metagenomics, enabling the study of genetic material directly from environmental samples. Its applications include diagnosing rare genetic diseases, identifying cancer-related mutations, and advancing population genomics research.
Distinguishing Characteristics of DNBSEQ
DNBSEQ technology offers several characteristics that distinguish it in genomic sequencing. It provides high data accuracy, largely attributable to the DNA Nanoball formation process. Each DNB contains multiple copies of the original DNA fragment, allowing for redundant sequencing of the same template. This inherent redundancy provides a built-in error correction mechanism, leading to more reliable base calls.
The technology also delivers high throughput, processing a large volume of samples and generating substantial amounts of sequencing data quickly. For instance, the DNBSEQ-T7 platform can generate up to 7 terabytes of data per day. This high capacity makes it suitable for large-scale genomic projects. The patterned array flow cells contribute to this efficiency by enabling a high density of DNBs to be sequenced simultaneously, optimizing chip utilization.
DNBSEQ offers cost-effectiveness due to its efficient use of reagents and a design that minimizes the need for expensive DNA quantification instruments. The technology also demonstrates reduced optical duplication errors, where a single DNA molecule is incorrectly read as multiple distinct molecules. This reduction is achieved through the precise loading of individual DNBs onto discrete binding sites on the patterned array, which helps prevent interference from neighboring nanoballs.