Complete Genomics PIONEERING THE FUTURE OF AFFORDABLE GENOMIC SEQUENCING TECHNOLOGY

In the vast landscape of genomics, one company has emerged as a pioneering force, driven by a visionary scientist and his unwavering commitment to scientific innovation. Founded in 2005 in Silicon Valley, Complete Genomics has been at the forefront of revolutionizing high-throughput massively parallel sequencing technologies. Led by CoFounder and Chief Scientific Officer Dr. Radoje Drmanac, one of the founders of the field of genomics, the company has relentlessly pursued its mission to make routine whole human genome sequencing (hWGS) accessible and affordable.

With a career dedicated to improving DNA sequencing on a large scale, Drmanac’s groundbreaking work was recognized in 1987 when he received a grant from the US Department of Energy (DOE) in his native country of Serbia. This grant aimed to enable studying the impact of radiation on genetic mutations by sequencing the whole human genome. Leveraging this opportunity, Drmanac and his team relocated to the DOE’s Argonne National Laboratory near Chicago in 1991 to further develop sequencing by hybridization technology using the DOE grants.

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CO-FOUNDER AND CHIEF SCIENTIFIC OFFICER, COMPLETE GENOMICS

Drmanac’s visionary ideas were ahead of their time, as he proposed massively parallel sequencing in 1988, long before the completion of the human genome project. With the completion of the genome sequencing milestone, these technologies, along with sequencing by synthesis and Complete Genomics’ combinatorial sequencing by ligation chemistries, became more usable, making routine and affordable individual genome sequencing a reality. This served as the driving force behind Drmanac’s decision to establish Complete Genomics in 2005, securing funding and commencing operations in 2006.

Complete Genomics quickly established itself as a leading innovator in the field, offering end-to-end multi-omics platforms encompassing genetic sequencing and laboratory automation.

The company took pride in developing and manufacturing a full spectrum of instruments, catering to various sequencing needs. Under Drmanac’s guidance, Complete Genomics introduced its patented DNA nanoball-based sequencing technology, known as DNBSEQ™. This revolutionary technology, featuring DNA NanoBalls (DNBs) with no clonal errors and high signal density on patterned nanoarrays, significantly improved detection accuracy and efficiency. Drmanac remarked, “DNBSEQ sequencing technology has 2 to 3 times fewer indel errors than PCR clusters.”

Complete Genomics continued to push boundaries by expanding its product offerings to include a range of genetic sequencers* tailored to different throughput requirements. Drmanac highlighted, “Our pure business model is to provide superb - complete, powerful, and truly affordable - sequencing solutions to sequencing labs.” From the portable DNBSEQ-E25RS* to the ultra-high-throughput DNBSEQ-T20x2RS*, Complete Genomics’ instruments offered faster, cost-effective, and more accurate sequencing capabilities. The company also provided automation solutions for sample and library preparation and downstream bioinformatics tools, ensuring a comprehensive sequencing experience.

In 2023, at the prestigious Advances in Genome Biology and Technology (AGBT) General Meeting, Complete Genomics made headlines by introducing the DNBSEQT20×2RS*. This groundbreaking genetic sequencer boasted the ability to produce up to 50,000 whole-genome sequences per year, priced below one hundred dollars per genome. Drmanac emphasized the significance of this achievement, stating, “With our affordable sub $1/Gb cost of sequencing, many new applications will be open, making sequencingbased health monitoring and disease prevention at the molecular level accessible for all.”

Complete Genomics’ dedication to making high-quality sequencing affordable has positioned the company as a leader in the genomics landscape. Drmanac expressed pride in its differentiation from competitors, stating, “Based on our patented DNBSEQ and many other technologies, Complete Genomics offers high-quality sequencing at a lower cost.” This affordability has paved the way for a paradigm shift in genomics, enabling researchers and medical professionals to transition from partial genome analysis to whole genome analysis for rare disease detection, cancer treatment selection, and other transformative applications.

With their special DNA barcoding technology, stLFR**, which provides “Complete WGS” by adding haplotype phasing and improving the accuracy of variant detection, Complete Genomics has further enhanced the capabilities of their DNBSEQ-enabled real PCR-free WGS. Drmanac emphasized that a low cost DNA sequencing not only allows for deeper sequencing per sample but also facilitates broader use on a larger number of samples, yielding more informative results in various genomic applications. Ultimately, this accessibility and affordability of genomic data promise to advance human healthcare primarily through disease prevention and an extension of healthy living.

In the ever-evolving world of genomics, Complete Genomics stands as a testament to Dr. Radoje Drmanac’s visionary leadership and tireless pursuit of affordable and comprehensive sequencing solutions. With its unwavering commitment to innovation, Complete Genomics continues to shape the future of genomic research, revolutionizing healthcare and transforming lives globally.

Driving Innovation: A Visionary Mission and Cutting-Edge Technology

“Our vision and mission to advance genomics and improve lives through unrivaled and complete sequencing solutions drives innovation within the company,” says Dr. Drmanac. The company’s unwavering commitment to this vision has led to substantial investments in research and development, attracting and nurturing top talent, and organizing advanced research initiatives. “You cannot have a mission to lead innovation without heavy investment in R&D,” Dr. Drmanac emphasizes.

The technology at the core of Complete Genomics’ success is its revolutionary platform, DNBSEQ™. “DNBSEQ™ offers numerous advantages that allow for scalability, exploration of new applications, and fast-paced development,” explains Dr. Drmanac. It serves as the bridge between the company’s visionary mission and its cutting-edge innovations. The energetic and fearless teams at Complete Genomics work tirelessly to bring these innovations to life, continuously pushing the boundaries of scientific discovery. “When you have teams that can do that, then you get this fast development,” Dr. Drmanac marvels.

According to Dr. Drmanac, the biggest challenge faced by Complete Genomics is the diversity of applications and the rapid change in the genomics landscape. “Covering and supporting national genome projects, health monitoring, single-cell analysis, and more, require significant effort and sophistication,” he highlights. The company must integrate lowcost sample and library preparation techniques, including DNA barcoding from thousands of single cells while providing cost-effective secondary analytics tools. Meeting these challenges demands a complete and affordable solution without compromising quality.

The genomics industry is highly competitive, with several companies vying for market share. Dr. Drmanac acknowledges that technology, cost, and service quality are crucial factors in maintaining a strong position in the industry. “Complete Genomics fosters a competitive marketplace in the US, offering a range of products, including high-end machines,” he says. By empowering customers with choices and encouraging innovation, Complete Genomics ensures that research and medical genomics labs have access to state-of-the-art solutions.

Advancing Genomic Sequencing for Precision Medicine and Beyond

“Genomic sequencing, a laboratory method used to determine an individual’s genetic makeup, holds immense potential for the future of healthcare and precision medicine,” highlights Dr. Drmanac. With efficient large-scale DNA sequencing, scientists can gain deeper insights into diseases like cancer, enabling improved prevention, diagnosis, and treatment strategies. The efficiency of massively parallel next-generation sequencing is paramount in unlocking the full potential of personalized precision medicine, where an individual’s own genetic information can guide disease prevention, diagnosis, and treatment, including measuring gene activities in immune and other cells.

Complete Genomics boasts several patented sequencing technologies that play a vital role in advancing genomic research:

1. DNBSEQ: This exceptionally costeffective and accurate technology enables unique spatial tissue analysis with subcellular precision. It empowers researchers to delve into the intricate details of tissue differentiation, functioning, and adaptation to the environment at the molecular level.

2. CoolMPS: This technology offers accurate, longer, and cost-effective reads using basespecific antibodies, enhancing the quality and depth of sequencing data. It provides researchers with a valuable tool for comprehensive genetic analysis.

3. stLFR**: With advanced DNA barcoding capabilities for next-generation sequencing (NGS), stLFR enables more complete genome sequencing, including parental variant phasing. This enhances diagnostic accuracy and improves our understanding of genetic variations.

Dr. Drmanac emphasizes the importance of fully understanding the genomic programs not only of our own species but also of thousands of other crucial species, particularly for advancements in agriculture and the green economy. “Enormously large sequencing datasets, coupled with advanced artificial intelligence and synthetic biology techniques such as genome editing, are essential for unraveling how genomic programs control tissue differentiation, functioning, and adaptation at the molecular level,” he explains. The analysis of billions of samples, from inherited genomes to gene activity in single cells and microbiomes, is necessary. Complete Genomics is dedicated to accelerating this research effort by investing in research and development and leveraging the expertise of its teams. They are continually advancing the capabilities and cost-effectiveness of their sequencing technologies, including DNBSEQ, CoolMPS, stLFR**, advanced PCRfree WGS libraries and single-cell barcoding, to enable efficient and comprehensive multi-omics sequencing at an unprecedented scale.

The availability of more affordable sequencers and consumables is a game-changer, as it enables wider access to comprehensive sequencing tests for various applications. This accelerates the development of precision medicine and healthcare by employing molecular health monitoring to prevent and treat diseases more effectively, ultimately saving lives and extending healthy living. “Complete Genomics is committed to advancing the field of genomics through cutting-edge sequencing technologies, pushing the boundaries of what is possible in precision medicine and beyond,” pinpoints Dr. Drmanac.

Driving Innovation in Genomic Sequencing: The Complete Genomics Way

Since its inception, Complete Genomics has been at the forefront of advancing innovative and powerful massively parallel sequencing (MPS) technologies and solutions. Dr. Drmanac says, “Innovation is ingrained in the company’s DNA and is the driving force behind our superb products and unmatched technology advancements. We place significant emphasis on research and development, including the recruitment, training, and retention of top talent. The core teams of biochemists, engineers, and analysts at Complete Genomics have been working together for 10-25 years, fostering a culture of collaboration and innovation.

In addition to its key technologies, Complete Genomics has developed Patterned Nanoarrays for highly efficient MPS, a sensor-based portable sequencing platform that requires no illumination or optics, advanced fluidics to reduce reagent consumption, and pivotal library preparation technologies. Their product portfolio also encompasses automated sample processing for a wide range of omics studies.

“Innovation is a constant journey at Complete Genomics. It is deeply ingrained in our company

Since its inception, Complete Genomics has been at the forefront of advancing innovative and powerful massively parallel sequencing (MPS) technologies and solutions culture, and we continually strive to push the boundaries of sequencing and genomics applications,” emphasizes Dr. Drmanac. The company’s dedication to innovation is evident in its ongoing efforts to refine all aspects of sequencing technology, with the ultimate goal of achieving ‘instant error-free sequencing at no cost’. While this may be a humorous aspiration, it reflects Complete Genomics’ unwavering commitment to driving innovation and pushing the boundaries of what is possible in genomics.

At Complete Genomics, innovation is not limited to technological advancements alone. The company’s investment in talent and fostering a collaborative environment ensures that groundbreaking ideas are nurtured and transformed into reality. By fostering a culture of innovation, Complete Genomics remains at the forefront of the genomics industry, consistently delivering cutting-edge solutions that empower researchers and advance the field of genomics. “Innovation never stops at Complete Genomics,” claims Dr. Drmanac, underscoring the company’s commitment to driving progress and pushing the limits of genomic sequencing.

Unleashing the Power of Genomic Sequencing: Impacting Global Health and Environmental Monitoring

Complete Genomics’ high-efficiency and innovative equipment has played a crucial role in detecting and tracing the Omicron variant in over 70 countries. Dr. Drmanac shares, “All around the world, our cutting-edge technology has been instrumental in safeguarding local communities against the spread of this highly transmissible variant.”

The DNBSEQ-G50RS *sequencer and MGISP-100RS automation system, developed by Complete Genomics, played a pivotal role in the early detection of Omicron fragments in wastewater samples collected across Cape Town, South Africa..

In China, the ultra-high-speed DNBSEQ-G99* sequencer supported the China CDC in detecting the first imported case of monkeypox in Chongqing. Within a remarkable timeframe of 11.5 to 16 hours, from sample library preparation to virus sequencing and assembly analysis, the DNBSEQ-G99* provided invaluable insights for swift public health intervention.

Harnessing the power of DNBSEQ technology, metagenomic sequencing successfully identified the primary pathogen responsible for severe psittacosis in a patient’s body fluid samples. This breakthrough in diagnostics showcased the potential of genomics in unraveling complex infectious diseases and guiding targeted treatments.

Australia has also benefitted from using DNBSEQ technology, as Murdoch University scientists established an advanced genomics platform to support local growers in overcoming industry challenges and enhancing the performance and value of popular fruit crops. By leveraging the capabilities of Complete Genomics’ technology, Australian growers are safeguarding the country’s food supply and meeting the increasing global demand for high-quality food.

Complete Genomics’ commitment to innovation is further exemplified by the development of the DNBSEQ-E25RS*, a portable sequencer resembling the size of a coffee machine. These no-optics sequencers, which can be operated outside of traditional laboratory settings, are ideal for biological monitoring in various environmental samples, including plants, animals, and humans.

“Through unrivaled innovations in massively parallel sequencing (MPS) and other sequencing and related technologies, our mission at Complete Genomics is to make sequencing solutions truly accessible,” explains Dr. Drmanac. The company’s dedication to affordability in disease prevention tests, paves the way for better healthcare accessibility, even in low-income populations.

By leveraging the power of genomics and pushing the boundaries of sequencing technology, Complete Genomics continues to make a profound impact on global health and environmental monitoring. Through their commitment to innovation and accessibility, they are revolutionizing the healthcare landscape and fostering a healthier, more sustainable future for all.

Pioneering the Future of Sequencing Technology: Advancing Quality and Affordability

“Since inception, we have maintained a steadfast focus on research and development (R&D) and continuous innovation in sequencing technology, sequencer engineering, and laboratory automation,” explains Dr. Radoje Drmanac, Co-Founder and Chief Scientific Officer of Complete Genomics. This unwavering commitment to pushing the boundaries of technology drives their mission to provide global users with more powerful and comprehensive sequencing solutions, enabling groundbreaking scientific and medical breakthroughs.

The proprietary technology platform developed by Complete Genomics for highthroughput, cost-effective, and accurate whole- genome sequencing remains unparalleled in the industry. The company’s dedication to advancing their DNBSEQ-based real-PCR free WGS, incorporating complete haplotype phasing and accurate reading of all genes through longer MPS reads, continues to set new standards in genomic research. With the continuous improvement of special DNA barcoding and the stLFR** library preparation, Complete Genomics aims to read triple-repeat expansions, differentiate real genes from pseudogenes, and distinguish inherited variants from somatic variants. This groundbreaking approach, known as “CompleteWGS,” aims to make whole-genome sequencing accessible and affordable to all.

In addition to advancements in technological performance, Complete Genomics recognizes the importance of cost efficiency in the gene sequencing industry, particularly in the context of precision medicine and precision health. By optimizing processes, achieving economies of scale, and leveraging their expertise in high-throughput and portable sequencing, as well as laboratory automation equipment, the company is able to offer competitive pricing. This costeffectiveness has resonated with customers across various sectors, supporting the advancement of precision medicine, precision agriculture, and precision health.

The future of genomics and genomicsbased healthcare is on the cusp of another revolution, driven by increasingly efficient sequencing and the resulting knowledge about the molecular functioning of cells. To facilitate this progress, comprehensive, accurate, and affordable omics tests for advanced health monitoring are essential. Complete Genomics envisions a future where annual check-ups involve deep sequencing of thousands of single cells, circulating cell-free DNA (cfDNA), and microbiomes to monitor the functionality and aging of the immune system, gut, and other organs and tissues. Furthermore, conducting research on gene activity, alternative splicing, epigenetic changes, and somatic mutations through deep sequencing will play a vital role in the early detection of cancer and other diseases. Driven by the need for vast amounts of sequencing data, Complete Genomics aims to provide the most efficient and cost-effective massively parallel sequencing (MPS) with unparalleled accuracy.

Through continuous innovations, including higher-density DNB arrays, more efficient reagents, and microfluidics, Complete Genomics is confident in its ability to significantly reduce the cost of sequencing. The company aims to achieve a staggering reduction from the already unmatched sub $1 per gigabase to an astounding $0.1 per gigabase. Additionally, they anticipate extending MPS read lengths from the current 400 bases to 700 or even 1000 bases, revolutionizing MPS capabilities and enabling more comprehensive whole-genome sequencing, cDNA sequencing, and longer amplicon sequencing.

As Complete Genomics continues to forge ahead in the pursuit of quality and affordability, its innovative sequencing technologies will shape the future of genomics and drive advancements in healthcare, agriculture, and various industries. With their sights set on the horizon, they remain at the forefront of a transformative era fueled by efficient DNA sequencing and a profound understanding of cellular and molecular mechanisms of life.

* 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). Sequencers named with “RS” are FOR RESEARCH USE ONLY AND NOT FOR USE IN DIAGNOSTIC PROCEDURES.

** MGI’s stLFR products are Only for Sale in the United States, and for Research Use Only.