Science Report 008

Decoding the Language of the Genome 02

The Next Medical Revolution Could Come from Innovation in DNA Sequencing Technology

The genome is a set of nucleotide sequences that makes you who you are and different from everybody else.

Determining what your sequence looks like used to require enormous time and money. But, thanks to the immense advancement of sequencing technology since the first successful human genome sequencing nearly 15 years ago, we can now use so-called next-generation sequencers to analyze our genomes far more quickly, accurately and cost effectively than ever possible before.

With information on an astronomical number of genomes stored in databases, the big data is helping further advance genome science. It is also revolutionizing medicine and enabling improvements in multiple aspects of our lives from the environment to land and economic development.

With sequencing technology continuing to progress at a rapid pace, it promises to transform our ourselves. So, where is this all headed? Dr. Yutaka Suzuki, a human genome expert, will explain.

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Ask an Expert: Dr. Yutaka Suzuki (The University of Tokyo)

Dr. Suzuki is a professor at the Graduate School of Frontier Science at the University of Tokyo. He earned his bachelor’s degree in 1994 and his doctoral degree in 1999, both from the University of Tokyo. After working for RIKEN (Rikagaku Kenkyujo)’s Genome Science Center as research associate in 1999, he moved to the Laboratory of DNA Information Analysis at the Institute of Medical Science at the University of Tokyo in 2000 to serve as assistant professor and became associate professor in 2004. For the past 25 years, Dr. Suzuki has conducted research focused on transcriptome collaborated with his mentor, Prof. Sumio Sugano of the University of Tokyo. His research is aimed at gaining a systemic understanding of how genomic mutation manifests in the form of cancer, neurologic disorders and other types of diseases. Click here for more information on Dr. Suzuki’s laboratory.

Delivering Cutting-edge Medical Treatment Anywhere, Including the Middle of a Jungle

A handful companies that developed the next-generation sequencing technologies control the entire global sequencing market. This means that the base technologies that support the industry all come from these same companies. The monopoly translates into uniform research procedures, including how to verify experimental data and conduct follow-up experiments, says Prof. Suzuki.

“Having said that, next-generation sequencers present tremendous possibilities for further advancement and revolutionizing medical practice. We must decide how we want to benefit from the technology and put the research community on the right path toward that goal,” Prof. Suzuki says.

As a step to do just that, Prof. Suzuki has launched the “on-site genomic diagnosis” project to provide better medical access to people in undeveloped countries. The project’s goal is to develop a compact, portable sequencer that can be used anywhere to quickly identify the best course of treatment for patients and deliver it on the spot. One scenario would involve drawing blood from a patient suffering a high fever in the middle of a jungle and conducting high-speed sequencing of the patient’s genome conducted right on the site. The result would reveal not only what’s causing the fever, such as malaria and dengue, but also what strain or type of virus or parasite it is, whether it would respond to medication and what other underlying infections the patient may have.  One requirement for the sequencer, in addition to its portability and sequencing speed, is the ability to withstand tropical heat and elements, and Prof. Suzuki and his team are working to develop a group of technologies that would enable the use of sequencers in non-hospital, non-sterilized environments, including outdoors.

“These technologies have a surprisingly wide range of applications, including self-health check through genome sequencing of your own stool sample taken at home, discovering a new species during field research, verifying the origins of seafood like eel and other food products to prevent false claims and identifying individuals involved in a crime through genome sequencing of hair,” Prof. Suzuki says.

“Genomic diagnosis” could particularly be useful for quarantine checks at the airport, he says.

The prototype sequencer for genomic diagnosis is small enough to fit in your palm. The sequencer that Prof. Suzuki is shown holding here needs to be inserted into the specimen holder, which allows the user to read the processed data and analysis on one's personal computer.

Using Genomic Mutation as Weapons Against Cancer

When it comes to medical use of genomic information, whole genome sequencing is only the first step. Many researchers are now focused on finding out how someone’s DNA molecules are organized as a system in order to use that information to predict the person’s medical risks, or keep a disease from progressing.

Each living organism has just one set of DNA information, but mRNA that transcribes information from DNA for synthesizing protein can alter in response to various factors and can carry different information in different organs. Prof. Suzuki, who has studied mRNA transcriptome for many years, says analyzing gene readouts is useful in cancer diagnosis and treatment.

“Cancer is a disease that causes a transcriptome mutation. We can find out how a genome mutation affects gene expressions and what happens to it if we try to correct it with medication,” Prof. Suzuki says. “Causes and prognosis largely vary from patient to a patient because of the genome. This explains why there are 500 to 1,000 different types of lung cancers alone. Just because a medication worked for one patient, that doesn’t mean it will help another patient. Everyone has their own story, and we hope genomic mutation information will help us deliver individualized treatment.”

Single-cell sequencer that deciphers and provides genomic information of each separate cell.

Taking Out-of-the-box Approach to Expedite Drug Development

The Suzuki Lab is also working to develop methods for integrating sequencing results and prognosis obtained through computer simulations in order to make individualized genomic treatment a reality. Chemotherapy may kill 99 percent of cancerous cells, but the remaining 1 percent that doesn’t respond to the drugs often triggers a recurrence.

“It’s crucial to identify the 1 percent cell with high accuracy. We then need to perform genomic analysis of that cell and use the result for simulations,” Prof. Suzuki says.

In the meantime, “immune checkpoint inhibitors,” a new type of cancer medication that activates the patient’s immune system to attack cancerous cells, has drawn public attention in recent years. Prof. Suzuki points out that the ability to distinguish and isolate cells to target is important in this type of treatment, as well.

Prof. Suzuki holds a tray for a single-cell isolator/analysis machine. Trays are divided into microscopic sections that function as receptacles for separated cells, allowing the machine to read genomic information of each cell.

Single-cell Technology x Next-generation Sequencers for Cutting-edge Cancer Treatment

Single-cell technology refers to the technology for isolating and analyzing a single cell. When trying to analyze a genome sample with a next-generation sequencer, researchers normally mush cells before putting them through the machine. In case of cancer, however, they aren’t trying to evaluate the sample as a whole.

“In partnership with Dr. Ryoji Yao, principal investigator of the Division of Cell Biology, Cancer Institute, The Japanese Foundation for Cancer Research, we are conducting research on single-cell technology for isolating each cell and analyzing it with next-generation sequencers. Our initial focus is colorectal cancer,” Prof. Suzuki says.

The project is part of the “Platform for Advanced Genome Science” that uses revenues from genome sequencing to augment grants that support researchers. “We have high hopes that the project will elucidate how colorectal cancer cells are structured and particularly how would-be cancerous cells emerge and mutate,” Prof. Suzuki says.

A researcher operates a next-generation sequencer. A genome sample needs to be placed in the black box on which the researcher has her hands. The user can control the machine via the monitor and get sequencing information.

Platform for Advanced Genome Science: Support Network for Genome Analysis Research led by the Inter-University Research Institute

“Platform for Advanced Genome Science (PAGS)” is a project of KAKENHI, the Ministry of Education, Culture, Sports, Science and Technology (MEXT)’s Grants-in-Aid for Scientific Research program. PAGS provides cutting-edge genome sequencing and analysis technology to KAKENHI supported projects. The National Institute of Genetics (NIG), which is located in Mishima, Shizuoka Prefecture and is one of the Inter-University Research Institutes, serves as the central institution for PAGS in which various universities and research organizations participate to form a network. PAGS has helped various research projects generate multidisciplinary research outcomes to promote cutting-edge life science findings, as well as the advancement new genome technologies.

Interviewer: Rue Ikeya
Photographs: Yuji Iijima unless noted otherwise
Released on: Dec. 11, 2017 (The Japanese version released on July 10, 2017)

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