Interview with Dr. Radoje Drmanac on Sequencing Technology and the Future of Genomics
Dr. Radoje (Rade) Drmanac, Chief Scientific Officer and co-founder of Complete Genomics, is a research scientist and inventor in human genome sequencing. His work includes DNA sequencing-by-hybridization (SBH), genomic micro- and nanoarrays, combinatorial probe ligation, and long fragment read (LFR) methods for accurate whole genome sequencing and haplotyping from as few as 10 human cells. In 1994, he co-founded Hyseq (later Nuvelo), where he led efforts to discover and patent thousands of genes forming the basis of Nuvelo’s drug development pipeline. Prior to Hyseq, Rade was a group leader at Argonne National Labs (1991–1994) as part of the Department of Energy’s Human Genome Project. He completed postdoctoral studies in 1990 in Hans Lehrach’s group at the Imperial Cancer Research Fund in London and earned his Ph.D. in molecular biology from Belgrade University, where he also received his B.S. and M.S. degrees in molecular biology.
Q1. When were you interested in sequencing technology for the first time?
A: A long time ago, during my master’s degree. I was cloning a single gene and realised how slow and inefficient it was. It took a year to sequence just one gene. I thought there must be a better way—if we could sequence a whole genome, we would have all the genes at once. In 1987, I developed sequencing by hybridization, which was essentially the first massively parallel sequencing method. Instead of sequencing one piece of DNA at a time, we could sequence millions simultaneously using DNA arrays. The initial solution used micron-sized beads with emulsion PCR to generate clonal DNA clusters on each bead. After emulsion PCR, the beads were hybridized with labeled probes to read sequences. That 1987–1989 period marks the beginning of high-throughput genomics and large-scale sequencing.
Q2. What kind of advancements will sequencing technology bring to biological research, and how will it affect daily life?
A: Sequencing technology requires time to develop before it impacts medicine and daily life. Our genome affects all aspects of our biology—not destiny, but a complex program defining tissue function. The earlier we can read this program, the sooner we can predict and monitor our health.
High-throughput sequencing enables:
- Accurate reading of inherited genes to assess predispositions
- Health monitoring at a molecular level
- Cell-free DNA analysis to detect mutations
- Deep analysis of microbiomes
- Single-cell RNA sequencing to assess immune function
Technologies like PCR-free sequencing and stLFR allow us to assemble “perfect” genomes without relying on references. DNA barcoding and DNA microscopy provide nanoscale cellular insights. Collectively, these methods transform healthcare from basic metrics like blood pressure into molecular-level monitoring. Over the next 30 years, genomics will grow in accuracy, affordability, and application, unlocking preventive healthcare and personalized medicine.
Q3. What do you think of sequencing technology’s future development?
A: Costs have dropped from millions per genome to below $500, and MGI is aiming for a $100 genome. Affordable sequencing enables massive databases for AI-driven analysis of human genetics. Future development focuses on:
- Reducing cost and increasing throughput
- Improving accuracy with technologies like CoolMPS (unlabeled nucleotides)
- PCR-free libraries for error-free genome sequencing
- stLFR co-barcoding for haplotype-phased de novo assembly
The T7 instrument demonstrates higher density DNA nanoball arrays, enabling terabase-scale sequencing at lower cost. Rolling circle replication produces DNBs without PCR, eliminating clonal errors. PCR-free libraries on DNBSEQ platforms do not require molecular barcodes, increasing usable reads. stLFR allows unique co-barcoding of millions of fragments, enabling efficient haplotype-phased de novo assembly of personal genomes, as well as sequencing of hundreds of new species. Together, these advances promise virtually unlimited sequencing and the foundation for precision healthcare.
Q4. What is your most impressive moment at MGI, and do you have any wishes for the company?
A: Many moments have been exciting—from presenting BGISEQ-500 at the ICG Conference to launching MGISEQ-2000 and DNBSEQ-T7. The most rewarding part is seeing genomic applications improve health, including prenatal testing for newborns. My wish for MGI is to grow globally, make genome sequencing accessible to all children, and drive precision healthcare. The work at MGI is not about quick profit; it’s about improving lives. Genomics is enabling a new era—the DNA age—where extended, healthy lifespans become achievable, and everyone has the right to their genome.
