Sequencing and the Human Genome Project

This year marks the 20th anniversary of the completion of the first human genome sequence, mapped out on April 14, 2003. Initially a targeted effort to understand the impact of radiation on human beings, the Human Genome Project (HGP) set in motion countless advancements that have revolutionized healthcare—culminating in the sub-$100 genome available today. Having spent over three decades contributing to our collective understanding of the human genome, I look back at my achievements and those of my peers with great pride.

My Role in the Human Genome Project

My involvement with HGP began in 1987, precisely when the initiative was kickstarted. The US Department of Energy provided a $150,000 grant to improve genome analysis technologies, including sequencing. As part of HGP, I proposed and later moved to the US to develop DNA sequencing-by-hybridization, which enabled higher-throughput sequencing. Around this time, my idea of massively parallel sequencing (MPS) using DNA microarrays prepared by emulsion PCR on microbeads was also born.

In essence, HGP was about making a list of genome parts. At the time, we did not fully understand most of them, but the project created a foundation for sequencing more genomes. It made shorter reads more usable because we now had a reference, enabled exome and panel sequencing using capture probes, and proved that biology could scale up to “big science” projects—similar to sending humans to the moon.

This work also inspired me to start my own company, Complete Genomics, to maximize the potential of MPS.

Witnessing the Genomics Revolution

MPS was critical in enabling routine, affordable sequencing of individual genomes. Motivated to bring this vision to life, I founded Complete Genomics. In 2005, my team and I invented patterned arrays of DNA nanoballs (DNB), expanding MPS capabilities for more efficient and large-scale sequencing. Today, we call this core technology DNBSEQ™.

DNBSEQ™ sequencing arrays eliminate clonal errors and index hopping while generating higher signal density than traditional DNA arrays, leading to improved detection accuracy. With advantages such as increased accuracy, decreased duplicates, and reduced index misassignments, this technology is the backbone of all MGI sequencing instruments.

In 2010, Complete Genomics hit another milestone by delivering the first $5,000 genome using DNBSEQ™, demonstrating that routine, accurate whole-genome sequencing (WGS) was achievable. Later, we joined MGI, gaining the investment and resources to scale the technology further.

In 2016, as part of MGI, I developed CoolMPS sequencing chemistry, which introduces unlabelled nucleotides and fluorescent-labelled antibodies to recognize incorporated bases. This method avoids DNA “scars” that accumulate in traditional sequencing, improving accuracy and enabling longer reads.

Driving Down Sequencing Costs for Public Health

Genomics has advanced at an unprecedented pace, steadily driving down sequencing costs. MGI recently pushed the boundaries again by introducing the sub-$100 genome with the DNBSEQ-T20×2*, an ultra-high-throughput sequencer capable of reading up to 50,000 WGS per year for under $100 per genome.

From the first $5,000 genome to the $100 genome in 2020 and now the sub-$100 genome, the downward pricing trend is clear: routine genome sequencing for everyone is within reach. Looking ahead, I hope MGI will be the first to achieve a $10 genome, enabled by advancements such as:

• Higher-density DNB arrays to reduce reagent use
• Single-tube long fragment read (stLFR) technology for fully phased whole-genome sequencing
• Deeper sequencing of the immune system and microbiome to support predictive and preventive healthcare

Since the 1980s, the goal of unlimited genome sequencing has driven research forward. Once considered “big science,” HGP completed something few had imagined—and we are determined to push even further.

Genomics for All

In 2007, the first Asian personal genome was published in Nature, inaugurating an era of large-scale personal genomics. Since then, numerous government-funded population-scale sequencing programs have emerged, including:

• The 1,000 Genomes Project (2008)
• The UK’s 100,000 Genomes Project
• The Genomes of Icelanders

These efforts help researchers identify genetic factors linked to diseases, leading to better treatments and preventive measures.

MGI actively participates in National Genome Projects in Thailand, Indonesia, and Brazil, providing sequencing technology to advance personalized diagnostics, drug selection, and treatment in fields such as:

• Cancer
• Infectious diseases
• Rare and undiagnosed diseases
• Non-communicable diseases
• Pharmacogenomics

With MPS enabling more efficient sequencing worldwide, sequencing is now integral to almost every omics field. From measuring protein levels in blood to evaluating gene activity, the purpose of sequencing is shifting—from understanding genomes to disease prevention and treatment.

From witnessing the impact of the first human genome sequence to discovering the first disease-causing mutation in personal genomes at Complete Genomics, I have no doubt that genetic sequencing will continue to transform lives in unimaginable ways.

*Unless otherwise stated, 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.

Published 3 November 2025