Science Report 009

Decoding the Language of the Genome 03

How Will Genomic Discoveries Change Our World Views?

Thanks to the advancement of technology, we now sequence countless genomes every day, including personal samples and the DNA of living matter around us. All such data becomes aggregated to form big data, which gives us new insights into life. For example, we now know what separates humans from chimpanzees is a 1.23 percent difference in nucleotide sequences of the two species’ DNA. Big data also led to some revelations that resulted in a rewriting of the phylogenetic tree of evolution.

The genome provides scientific evidence useful to prove or disprove hypotheses. The demand for this versatile research tool continues to grow in research fields, many of which have had little to do with the genome until recently.

But what does this really mean for our future? How are researchers trying to leverage the technology? And how will our new discoveries change our perspective on life?

Dr. Yuji Kohara of the Database Center for Life Science will share his view.

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Ask an Expert: Dr. Yuji Kohara

Dr. Kohara is a specially appointed professor at the National Institute of Genetics(NIG) and the director of the ROIS’s Database Center for Life Science(DBCLS). He serves as the principal investigator of “Platform for Advanced Genome Science(PAGS)”, which is one of the Ministry of Education, Culture, Sports, Science and Technology(MEXT)’s Grants-in-Aid for Scientific Research program. After receiving a PhD’s degree in science from Nagoya University, he worked as a research fellow for Medical Research Council’s Laboratory of Molecular Biology in the United Kingdom. He joined the NIG as professor in 1996 and served as its director from 2004 through 2012. Amid the fast advancement of molecular biology, Dr. Kohara has worked to decode the connections between the genome and phenotypes. As data gathering and sharing are key to promoting genetic research, Dr. Kohara is also focusing on the development of integrated databases. Click here to visit the DBCLS’ website.

One Technological Breakthroughs After Another

Genomics is a fiercely competitive research field, where not only scientists but also technologists from around the world are racing to innovate. To put the speed of evolution in perspective, “a couple of major technological innovations emerge every five years,” according to Prof. Yuji Kohara of the National Institute of Genetics, who serves as the director of the ROIS’s Database Center for Life Science (DBCLS).

The industry-standard genome sequencer also needs to be replaced with a newer version every so often to keep up with technological advancements.

“As soon as a new machine becomes available, we must adopt it and adjust our procedures and operations accordingly,” Prof. Kohara says.

In other words, research labs would need to review and modify their entire research process, from what types of experiments to carry out to what samples to prepare to how to conduct analysis. Such reconfiguration requires high levels of expertise each step of the way.

In the meantime, genomic analysis as a research tool continues to make its way into various research fields.

“Researchers who weren’t even thinking about the word, ‘genomes,’ yesterday are suddenly talking about sequencing them today. We are seeing more and more of this,” Prof. Kohara says. “This trend is particularly noticeable in the environmental, medical and agricultural fields. The genomic analysis of river soils and bacteria, for example, can reveal interesting facts. Medical researchers are now interested in doing not only genomic diagnosis but also genomic analysis of intestinal bacteria. Agricultural researchers are looking to use genomic analysis for potential crop improvements.”

The demand for single-cell genomic analysis is also on a rise, Prof. Kohara says.

Genomic analysis of river soil and bacteria is particularly popular.

Individual labs only cannot do so much to catch up with rapid technological changes by themselves. But, what if there was a centralized system that pulls together all the expertise needed for making other important changes – such as software and hardware upgrade – and makes it accessible to labs?

This idea led to the launching of “Platform for Advanced Genome Science (PAGS).” PAGS is a project of the Ministry of Education, Culture, Sports, Science and Technology (MEXT)’s Grants-in-Aid for Scientific Research Program known as the KAKENHI program. PAGS makes cutting-edge technologies for genome and data analysis available to researchers when requested in order to help them carry out their KAKENHI research projects.

In 2000, a core-facility team was formed within a KAKENHI project called Grant-in-Aid for Scientific Research on Priority Areas. This team was the precursor to PAGS, according to Prof. Kohara. This team’s primary focus changed over time to aiding genomic research. It also redesigned its structure to facilitate multidisciplinary distribution of resources and technologies to become the NIG-led support system that it is today.

PAGS’s research support team coordinates resources and expertise that university labs request for their KAKENHI projects. The team assists universities with the alignment and maintenance of the latest equipment and technologies and conducts genomic analysis for some of the most advanced research projects. Prof. Kohara represents the PAGS.

“As PAGS's support team adopt newer equipment, it is becoming capable of sequencing genomes faster and more accurately than ever. Informatic scientists in PAGS's support team have access to more actual data through assisting university labs, which, in turn, is helping them improve their analysis skills,” Prof. Kohara says. “PAGS’s support team also coordinates a one-week on-the-job training program for students to gain necessary skills and better contribute to the KAKENHI projects for which they work. In other words, our team helps put KAKENHI labs and PAGS' support team on a path for continuous improvements.”

If You Want to Win the Competition, Build Databases

Genomic data is critical to life science research and becomes more so as data accumulates.

“In the game of big data analytics for genomic research, the one with the most amount of data wins,” Prof. Kohara says. “In addition to the U.S., places like China have mega-analytics centers. These are the places that get the largest amount of data because data naturally goes to analytic service providers. This explains why Japan needs to come up with a way to attract and compile more data, so the country’s life scientists have more data with which to work,” Prof. Kohara says.

But, in order to truly tap into the potential of genomic big data, one must have not only a substantial amount of data but also information that puts the data in context.

“For example, in order to use genomic big data for medical research, you need to link genomic data with epigenetics or medical records to glean knowledge from it,” Prof. Kohara says. “Although ‘we are all made from genomes’, all those bacteria and other life matter that live with us help shape us,” Prof. Kohara says.

Hologenome refers to sampling and analyzing of genomes in the entire environment that surrounds us, including bacteria outside our bodies and those inside our organs, such as the stomach.

As hologenome research continues to advance, the line between the human and the environment may become more ambiguous. We may not be just the bodies that are covered with the skin after all; things around us could also be considered as a part of us.

“That can also lead to the profound question of what life is and what you consider as an individual.”

National BioResource Project, the Database for All Organisms from Prokaryote to Humans

National BioResource Project (NBRP) Official Website

More than 28,000 research papers have used NBRP resources.

The purpose of National BioResource Project (NBRP) is to collect, preserve and share samples of 30 different bioresources that are regarded as strategically important for Japan’s research projects.

Bio-resource refers to “systems, groups, tissues, cells, and genetic materials of animals, plants, and microbes and their information as research and development materials” according to the NBRP website.

The Genetic Strains Research Center at the National Institute of Genetics (NIG) serves as the NBRP’s portal for information and model species. Dr. Shoko Kawamoto, associate professor at the Genetic Strains Research Center, was recently appointed to lead the NBRP.

“We are trying to build a bio-resource database that allows for cross-species search,” Dr. Kawamoto says. “That means the database has to have sequencing data of all model species’ genomes as well as analytics on the bulk of those genomes.”

Once common denominators among different species become clear, it enables replication of a scientific experiment with multiple species. For example, when a newly developed variety of wheat grows well, one might be able to create a same type of variety of another monocot.

“It might also allow replacing mice and rats with their counterparts that are structurally much simpler, such as zebrafish and drosophila, for experiments in research on human diseases. There is a growing expectation that this would help speed up research on rare diseases,”Dr. Kawamoto says. “The NBRP could potentially match clinical researchers with drosophila researchers,” she says.

In addition, the NBRP serves as a Japanese arm of the Global Biodiversity Information Facility (GBIF), an “open-data research infrastructure” that gathers and provides access to information about all kinds of species to better understand ecosystems around the world. The NBRP has a biodiversity registry through which people can report what species lives and where.

“Research data on spiders on the island of Yakushima and swallows nestling in the Kinki region are examples of what we’ve collected through the registry,” Dr. Kawamoto says.

But having an intelligent database may not help as much if researchers don’t know how to tap into it, says Dr. Kawamoto, who has the experience as a genetic researcher.

“Demand for personalized medical treatments is expected to grow. We are going to keep that in mind to build an open science type of database system that caters to the needs of end users like patients,” Dr. Kawamoto says.

Dr. Shoko Kawamoto, associate professor at the Genetic Strains Research Center, was recently appointed to lead the NBRP.

Interviewer: Rue Ikeya
Photographs: Yuji Iijima unless noted otherwise
Released on: Jan. 25, 2018 (The Japanese version released on Aug. 10, 2017)

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