AsianScientist (Apr. 14, 2023)–Exactly two decades ago, an international team of scientists made history when they produced a complete sequence of over 90 percent of the human genome. The Human Genome Project (HGP), launched in 1990, was designed to push the boundaries of genome sequencing technologies and offer researchers a ‘map’ to the building blocks of humanity.
The task of sequencing the whole human genome involved 20 universities and research centers from six different countries—the groups were collectively known as the International Human Genome Sequencing Consortium.
“In essence, HGP was about making a list of genome parts. At the time, we did not understand most of them, but nonetheless, there was a list,” said one participant of HGP Dr. Radoje Drmanac, currently the Chief Scientific Officer of global life science company, MGI, and Co-Founder of Complete Genomics. “It prompted this important demand for the sequencing of more genomes. It made shorter reads more usable because we now had a reference. It allowed exome and panel sequencing with capture probes and primers based on the genome sequence. It proved that biology was entering larger scale projects, much like sending human beings to the moon.”
Dr. Drmanac was involved in the project from the very beginning when he received grants from the US Department of Energy in 1987 in Serbia and in 1991 to move from Serbia to the US. He was tasked to further develop DNA sequencing by hybridization, which would enable more efficient higher throughput sequencing. Dr. Drmanac shared with Asian Scientist Magazine how he has witnessed the industry and its technologies transform in the last 20 years since the completion of the project.
Sequencing at scale
When the human genome was first sequenced, the entire process cost roughly US$2.7 billion. While the achievement was undeniably groundbreaking, there is always more to be done. The goal for genomic technologists at the time was to strive for more effective sequencing methods that would bring down costs and make the technology accessible for healthcare systems and researchers all over the world.
While working on improving sequencing technologies for the HGP, Dr. Drmanac also proposed massively parallel sequencing (MPS), or next-generation sequencing (NGS), a radically new sequencing that uses DNA microarrays prepared by an emulsion polymerase chain reaction (PCR) on microbeads.
In 2005, Dr. Drmanac and his team at Complete Genomics invented dense, fully loaded patterned arrays of DNA nanoballs that provide the highest efficiency and largest-scale MPS. Patented as DNBSEQ™, the technology is now used in all MGI’s current sequencing instruments. By 2010, Complete Genomics marked a major milestone and became the first to achieve a whole-genome that cost just US$5,000 using DNBSEQ™. This accomplishment signaled to the industry that routine, affordable and accurate whole-genome sequencing was possible.
“DNBSEQ™ sequencing arrays have no clonal errors or index hopping and generate higher signal density than regular DNA arrays for greatly improved detection accuracy,” explained Dr. Drmanac. “Its advantages include increased accuracy, decreased duplicates and reduced index misassignments.”
Toward genomics-powered public health
After Complete Genomics became a part of MGI, Dr. Drmanac continued to lead a team that further enhanced DNBSEQ™ capabilities. In particular, he developed CoolMPS sequencing chemistry in 2016. The technology is a unique chemistry that introduces unlabeled nucleotides and four fluorescent labeled antibodies in its sequencing process to recognize the incorporated bases—avoiding DNA ‘scars’ that can accumulate and affect the accuracy of traditional sequencing methods. By adding scarless bases in each sequencing cycle, this technology enables longer accurate genome reads and brings down the sequencing costs.
By combining the unique chemistry with the latest in the MGI arsenal, DNBSEQ-T20x2RS*, MGI boasts a new milestone—it can offer whole genome sequencing for under US$100 per genome at up to 50,000 genomes a year. Looking ahead, Dr. Drmanac continues to work toward even more affordable and accessible sequencing.
“In celebration of MGI’s seventh birthday this year, I’m hoping that we at MGI will be the first to sequence a genome for US$10 enabled by DNBSEQ™,” he said. “This downward trend in pricing shows that routine genome sequencing for everybody is possible and that there is great value in individual genome testing.”
As the cost of sequencing continues to decrease, the possibility of public health systems leveraging the technology rises. As countries move toward promoting precision medicine, more governments are funding population-scale sequencing programs that consider the nuances of each community’s unique DNA. Currently, MGI participates in national genome projects in Thailand, Indonesia and Brazil—offering a deeper understanding of the local populace.
Such projects serve as a foundation for the development of molecular health monitoring for disease prevention, personalized diagnostics as well as drug selection and treatment in the fields of cancer, infectious diseases, rare and undiagnosed diseases, non-communicable diseases and pharmacogenomic diseases.
“From seeing the applications of the first genome sequence, to discovering the first disease-causing mutation in personal genomes we sequenced in MGI and Complete Genomics, I have no doubt that genetic sequencing will do wonders as it touches every aspect of our lives,” Dr. Drmanac shared.
*Unless otherwise informed, StandardMPS and CoolMPS sequencing reagents, and sequencers for use with such reagents are not available in Germany, Spain, UK, Sweden, Italy, Czech Republic, Switzerland and Hong Kong (CoolMPS is available in Hong Kong).
For Research Use Only. Not for use in diagnostic procedures.
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