What does it mean to map the human genome?

Humans may be 99.9 per cent similar to one another, yet the miniscule remaining percentage spells all the difference – making one drug effective for one patient and life-threatening for another. Having a map of one’s genome means not having to rely on that one drug, therapy or treatment; it means getting the most appropriate treatment for one’s physiology.For global biotechnology company Macrogen, it simply means promising a better life that everyone deserves.

Much like a road map, a human genome map provides an array of valuable information. A landmark on a road not only shows where one traveller is positioned; it provides a reference point when travelling to a different direction. On a genome map, these landmarks are represented by DNA sequences, genes and regulatory sites that turn these genes on and off.

“Navigating a genome map enables scientists to plot the best way towards assessing the patient’s risk for diseases,” says Macrogen chairman Dr Seo Jeong-sun. “While most road maps today have been developed to unparalleled precision and accuracy, the human genome map has yet to chart new frontiers – and that is where Macrogen comes in.”

A venture spinoff from the Genomic Medicine Institute in Seoul National University, Macrogen envisions its contribution to society through the realisation of precision medicine.

Established in 1997 and listed on Korean Securities Dealers Automated Quotations or KOSDAQ in 2000, Macrogen has since grown its global presence. It has subsidiaries in Maryland, the United States, and in Kyoto, Japan. It also has branch offices in the Netherlands, Spain, Australia, Singapore and Daejeon, and various affiliated and investment companies worldwide.

Today, Macrogen remains focused on research and development (R&D), with its R&D personnel – including 34 doctorate degree holders – making up nearly half the company’s research workforce.

This strength has allowed the company to develop and commercialise various tools for genomic medicine using bioinformatics infrastructure, ranging from genome information analysis to functional genomics. Its intensive R&D has also launched Macrogen as a global leader in sequencing services. It is also recognised for commercialising genetically engineered mice production and cloning technologies.

The Genome Research Institute in Macrogen is key in developing core technologies for the company’s business. Among the institute’s breakthroughs are construction of the bacterial artificial chromosome clone map and the de novo assembly and complete phasing of a human genome through the Asian genome project.

The company’s R&D capability is complemented by some of the world’s advanced equipment and platforms that offer high-throughput DNA sequencing services within a short turnaround time. These include Illumina’s NovaSeq 6000, HiSeq X, HiSeq 4000/2500/2000, MiSeq, and PacBio’s RS II System that allow Macrogen’s sequencing capacity to exceed 8,000TB per year – and ensure the best genomic research solutions even for large-scale projects.


Translating big data and accelerating change in health care paradigm

Among Macrogen’s genome services are whole genome sequencing, exome and targeted sequencing, transcriptome sequencing and bioinformatics. Whole genome sequencing for humans allows scientists to detect variations in order to discover potential correlations to certain disease risks, and play a role as molecular biomarkers for disease diagnosis and prediction.

At a reduced cost per sample, the company’s exome and targeted sequencing enables selective sequencing of coding regions or the extensive sequencing of the enriched target regions of interest. Transcriptome sequencing, on the other hand, provides a collection of all the transcripts within a given cell – with the sequence of RNA, or ribonucleic acid, mirroring the sequence of DNA. Combining the advantages of computer science, statistics, mathematics and engineering, bioinformatics facilitates the study and process biological data.

With genome information, doctors can diagnose diseases that may be caused by genetic disorders – and develop an appropriate diagnostic panel. Therapy can be highly specific and customised with target drug matching and biomarker and drug discovery. It also makes the monitoring of recurring diseases much easier, while allowing for tailored health care for each genetic type.

Furthermore, it empowers scientists, doctors and patients to predict and prevent diseases through genetic analysis. Combined with big data, this drives a revolutionary technology that makes precision medicine predictive, preventive, personalised and participatory.

“Ultimately, big data will disrupt current business models and pave the way for a biotechnology revolution that will forever change the health care industry,” Seo says. “Much like how the information technology revolution and the internet changed everyone’s lives with open, free and accessible information in the 1980s, our innovations today will hopefully lay the foundations for inexpensive, yet the best possible care everyone deserves.”

For instance, colon cancer patients using conventional medicine may undergo generic, untargeted procedures such as chemotherapy or radiation. This nonspecific method may yield positive effects on some, no effect on others, and even adverse effects on a few patients due to their varying characteristics.

With precision medicine, every colon cancer patient is thoroughly analysed using individual blood, DNA, urine and tissue samples. Depending on each one’s biomarker diagnostics, a distinct and highly targeted therapy plan will be directed. This ensures not only the highest probability for positive effects, but lower costs for the patients in the long run.

“Our big goal is to help reduce health care cost levels to one-tenth of the current rates to make health care as affordable as possible in Asia,” Seo says. “Effectively and efficiently curing some diseases begin with the acquisition of individual genome information, which in turn feeds into the big data that we can then use to create better products, treatments and solutions.”


Understanding the Asian genetic fabric in pursuit of healthy living and longevity

Asia accounts for more than half the world’s population with more than 4.5 billion people. The number is staggering, but the reality is that modern medicine is still largely biased towards the Western market where genome information is far more available. Macrogen aims to remedy the situation by initiating a project that will sequence the genomes of 100,000 Asians in order to understand the population’s genetic fabric.

“Despite their number, Asians are underrepresented in current genomic studies and reference genome databases,” Seo says. “We know that the distinct genetic diversity prevalent in South and East Asia provides a valuable source of clinical insights that can unlock cures and treatments for all of mankind in rare and inherited diseases, and complex diseases such as neurological disorders, cancers and diabetes.”

The project – GenomeAsia 100K – is made possible through a non-profit consortium that envisions the promotion of genetic understanding of Asian populations to support research and discovery for healthy living and longevity.

Along with consortium co-founder Stephan Schuster at Nanyang Technology University and genomics-driven research and diagnostics company Medgenome, Macrogen has put together a team of leading bioinformaticians and scientists in the field of population genetics. Over the next three to four years, the initiative targets to cover more than 40 countries in Asia, including all its major ethnic groups. It will also build advanced analytical capabilities to analyse big data with the help of advanced data science and artificial intelligence.

“The project aims to create reference genomes for Asian populations, and then identify rare and common alleles associated with these populations,” Seo says. “Through this, we seek to understand the biology of diseases and enable new therapeutic solutions and alternatives that will have a resounding impact not only on Asia, but globally.”

Reinforcing Macrogen’s commitment to open information, the data from GenomeAsia 100K will be made available to the public. The database will be exclusively accessible to the consortium members for an initial period of 18 to 36 months for analysis, and then will be made available to the entire scientific community.

With partners in India, Singapore, the US and South Korea, GenomeAsia 100K is open to more sponsors and scientific collaborators. It is also seeking partners to take leadership roles in other Asian countries including Pakistan, Bangladesh, Sri Lanka, Malaysia, Indonesia, Myanmar, Nepal, Bhutan, Thailand, Vietnam, Laos and Japan.


Taking the bottom-up approach with partners towards a better world

To achieve its lofty ambitions, Macrogen believes that close cooperation between public and private sectors must be deepened and strengthened through a bottom-up approach where progression comes from individuals to the whole society.

“The whole world is connected,” Seo says. “Macrogen works to help people live in a better world – with the assistance and support of potential investors, collaborators, technical institutes and everyone else who shares our philosophy to change the world with goodwill.”

Marking its 20th anniversary this year, Macrogen also plans to open more offices in key locations such as Hong Kong, and work with even more partners who can help achieve its bigger, much more challenging pursuits.

“Next to our Asian project, our ultimate dream is to sequence therapeutically important genes such as BRCA in 7.5 billion people on Earth at an extremely affordable price of US$50 per person. This will help everyone have a chance at a better, healthier life and a disease-free world,” Seo says. “Like-minded, equally driven individuals and organisations are welcome to partner with us in pursuing such bold aspirations.


View at South China Morning Post