Integrating Cutting-Edge Genetics with Genetic
Resource Information for Research and Society

KAWAMOTO, Shoko Associate Professor

Genetic Informatics Laboratory,
Department of Informatics.

Ph.D. (Science) (Osaka University). In addition to running the “National BioResource Project,” which integrates the collation and supply of Japanese bioresources,
Kawamoto conducts research on how to make the database of genetic resource information useful for society, mainly in the field of genetic medicine. She
specializes in genome biology, human genetics, and life, health, and medical informatics. Concurrently, she is also an Associate Professor at the Database Centerfor Life Science, ROIS.

Kawamoto carries out a wide range of research, particularly on how to extract data from model organisms and apply
such information to human genetic medicine. While specializing in mammals, Kawamoto leads a project to collect,preserve, and provide 31 bioresources to other researchers around the world. Furthermore, she acts as a Japanese
node of the international network Global Biodiversity Information Facility, a network which collects “biodiversityinformation” in nature. Moreover, the challenge of applying fundamental research on model organisms to the raredisease research has also begun under the AMED program named IRUD-Beyond starting in FY2017. In the age of thegenome, Kawamoto addresses how to accelerate progress in biology, how to contribute to society through biologicalresearch, and how to pioneer a new integrated field of biology. She drives each project with such passionate interest.

Development of databases is essential

In 2017, Kawamoto took charge of a project called the “National
Bioresource Project (NBRP),” which collects, stores, and provides toresearchers bioresources of various model organisms, such as
mouse and rice. She says, however, that she considers that there is
an issue with the database because of the lack of horizontal
connections within the database; in other words, genes from different
species cannot be fully compared in the database. “For instance,
when you’re looking at a plant genome from the viewpoint ofbreeding, it is important to be able to distinguish between a genewhich is evolutionarily common to most plant species and which geneis, say, unique to monocotyledonous plants such as rice, wheat, andbarley? Without such annotations, even if breeding using this genesucceeds with one plant species, it is impossible to predict whether
the success can be achieved for other species.”

Kawamoto started her research career as a molecular biologist when
she was a university student. She looks back: “Because it was a time
when genome research had just started, I had to have a point of viewon biology through looking at thousands or tens of thousands ofgenes (giggling).” As is widely known, a tremendous amount of
human genome information continues to be produced, in addition to
the large amounts of genomic information available on modelorganisms, including Drosophila, which can be browsed by everyone.
“In order to elucidate the function of a gene, it is extremely important
to identify which elements are the same and which are different
between different species by comparing the same gene between
different organisms,” says Kawamoto. In other words, we need to ask
the appropriate questions of the enormous genomic datasets whichhave already been obtained to extract biologically meaningful
information.

Another reason for this loss of connectivity also resides in the biology
research papers themselves. Kawamoto collects scientific papers

1Connecting researchers of genetic
medicine and model organisms bycooperating with the Japanese Agency
for Medical Research and Development

containing research data using the resources of the NBRP. “A hugeamount of scientific knowledge has been accumulated in papers. It isnecessary to collect evidence in a comparable form in order toanalyze the data computationally,” she says. However, papers often
only describe the point that the researcher thinks is importantqualitatively. There is no standard format of describing phenotypes ina manner that is comprehensive to some extent and shared byresearchers. “Genetics is composed of the genotype and thephenotype. However, the phenotype could not be easily compared
between two organisms before.”

In November 2017, a research project entitled “Japanese Rare
Disease Models and Mechanisms Network (J-RDMM)” started with
NIG as the representative institution under the Japan Agency for
Medical Research and Development (AMED). Simply stated, it is “aproject to investigate the cause of genetic diseases using modelorganisms.” NIG has long contributed to this field in terms of genetic
resources and database development of model organisms.
Kawamoto is one of the key working members of the project, in which
NIG is demonstrating its research strengths.
Kawamoto describes her research strategy as follows. “I will call onmodel organism researchers nationwide and ask them to register toparticipate in research on intractable and rare genetic diseases tocollaborate with clinical researchers. Because clinicians specializingin hereditary diseases are well aware of “which tissue should bechecked at what time” to characterize the symptoms of the patient,
we will ask them to submit a request for the model organism that theywant to be analyzed based on the type of genes presumed to beresponsible for the hereditary disease in question. On the other hand,
I will request the model organism researchers to propose an efficient
analysis method for the gene responsible, depending on the
biological process they are studying. We began to create suchcollaborative groups, comprising medical researchers and modelorganism researchers in April 2018 and now, we have approximately
50 active collaborative groups. Our goal is to output some results forapproximately 50 diseases in the coming year.”Connecting rare human genetic
diseases and Drosophila
Surprisingly, Kawamoto once kept her distance from bioinformatics
research that she says “it has been my long-term project which I feel
is so important.” This reluctance was because of her concern that “nomatter how informative the database is, how can we use it for
research and to help society?” While conducting research on genetic
medicine as a genetic counselor, she came across the idea of “usingmodel organisms such as Drosophila to help elucidate rare genetic
diseases in humans,” and that made her think that “I could somehow
contribute because I had an interest in a theme concerning diseasemodels in mammals.”Moreover, Kawamoto predicts a lot of applications for this strategy
beyond genetic medicine. “In the near future, you may receive
thousands of pieces of information from the results of your healthexamination. I hope we will develop fundamental technology that willallow us to examine and understand all these components of the life
system in an integrated way. As a first step in the development ofsuch a system, my interest in the bioresource work, that can connect
diseases to organisms in various ways, never runs out.”

When investigating a rare genetic disease using a next-generation
sequencer, she says that there are situations in which the causative
gene change can be identified for genetic diseases, of which only a
few cases exist in the world. It is not difficult to obtain the treatment
information of other patients if the disease affects tens of thousandsof people. However, it is quite difficult to find two people who have thesame change in a specific gene in the case of a rare disease. “Mousehas been a key animal for disease models. However, a mouse is amodel organism that, relatively speaking, is expensive to study.
Therefore, not many experiments can be done. I wondered if we
could accelerate the experimental elucidation of rare genetic
diseases in humans using a model organism with a short generation
time such as zebrafish or Drosophila.” According to Kawamoto, suchorganisms are useful for research on rare genetic diseases and areexpected to use understanding the etiology of the disease. “I foreseea scene where a physician explains evidence from Drosophila to thepatient while showing them a paper on a medical website, and thatsort of scenario will become increasingly realistic from now on.”2Genetics is important
While working on such a complex project, Kawamoto strongly feelsthat in the environment of NIG “Again, genetics is important.”“Genetic information no longer refers simply to individual genes but
rather to integration of the information from the metabolomics and all
the other -omic technologies derived from the genome. Without being
able to analyze and understand the interactions associated with theg e n o m e i n t h e f o r m , s a y, o f t h e g e n e t i c b a c k g r o u n d a n denvironmental factors, it is difficult to predict what effect a gene (andits mutants) would have even from an experiment performed in alaboratory under controlled conditions.”“Bioinformatics” is a field in which life science and information
science merge and in which Kawamoto has been involved since heruniversity days, and the field has advanced dramatically in recentyears. The whole genome of numerous organisms has beensequenced and the genes annotated and now, anyone can accessand browse such data. As Kawamoto says: “That is whybioinformatics has to connect more research institutions andresearchers and contribute to genetics through a heuristic use ofknowledge from experiments using computation.”Interviewer:
Rue Ikeya, Research Organization of Information and Systems
Photographer:
Mitsuhiko Kurusu, Office for Research Development
September 20183