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Overview of Bioinformatics Research in Japan
Kenta Nakai, PhD
Human Genome Center, the Institute of Medical Science, the University of Tokyo, 4-6-1 Shirokanedai,
Minato-ku, Tokyo 108-8639, Japan

A Brief Sketch of Bioinformatics Activities in Japan

Japan has a long tradition of what is now called bioinformatics research. Notably, Prof. Minoru Kanehisa, the first president of the Japanese Society of Bioinformatics (JSBi), participated in the historical start of the GenBank database in the US and has led the construction of KEGG (Kyoto Encyclopedia of Genes and Genomes), which is now a world famous database for bioinformatics research. In addition to JSBi, there are several bioinformatics-related societies, including the CBI (Chem-Bio Informatics) society and the Japan Society for Omics-based Medicine. These three societies have held joint annual meetings for several years. Moreover, with the rapid progress of the Next Generation Sequencing (NGS) technology, an association of those who work in NGS has attracted many young bioinformatics researchers. For the integration and maintenance of various databases, a national center (DBCLS: DataBase Center for Life Science) also exists and collaborates with traditional database centers, such as DDBJ (DNA DataBank Japan) and PDBj (Protein Data Bank Japan).

Bioinformatics for Personalized Medicine: A Hot Topic

It goes without saying that the NGS technology has exerted the largest influence on bioinformatics lately. It was only ten years ago that people regarded DNA sequence analysis as an obsolete field. Nowadays, the long awaited goal of sequencing the whole genome of an individual at a cost of $1000 has been (almost) achieved, and sequencing projects such as those for sequencing 100 thousand or a million genomes have been announced. Personal genomics projects will be helpful in finding the association between sequence variations and phenotypes, such as diseases and adverse effects against drugs, in a comprehensive manner; and these data will open the door to the new era of personalized medicine, where medical doctors can optimize their treatments based on the genomic information of each patient. In Japan, several groups have been contributing within some international consortiums: a group including RIKEN is a member of the International Cancer Genome Consortium, and Tokyo Women’s Medical University is a member of the International Collaboration for Clinical Genomics. In addition, in Japan there are several cohort studies, where the genome sequencing of volunteers is performed while also keeping record of their clinical information. One such example is the BioBank Japan Project, conducted by RIKEN, and another is the cohort study conducted by the Tohoku Medical Megabank Organization, which was established after the Tohoku earthquake in 2011. It is believed that with the achievement of the $1000 genome, many changes will occur in our society and industry. For example, the so-called Direct To Consumer businesses of providing medical diagnosis from sample provided by each consumer have started or are being announced. Such activity may create new demands for bioinformaticians in Japanese industry.

Introducing Our Project on Regenerative Medicine

Regenerative Medicine is one of the fastest-growing fields in medicine and has especially attracted much attention in Japan, partly because a Japanese scientist, Prof. Shinya Yamanaka, had invented the iPS cells and was awarded the Nobel Prize in 2012. Supported by a grant from the Ministry of Health, Labour and Welfare, I have been leading a bioinformatics-related project on regenerative medicine, entitled “Research toward building a platform for clinical applications of regenerative medicine using human stem cells” since 2011. The aim of the project is to study and construct an effective infrastructure for the member researchers in the field to share their unpublished raw data/information, using information and communication technology. Utilizing such a platform, project members will be able to avoid redundant studies, to use the data deposited by another member for their own research, and to establish the consensus criteria for assessing the quality of stem cells. With these activities, the level of research on regenerative medicine in Japan will be boosted and become more competitive in the world. Members of this project consist of representative research groups from eight institutions, including the Center for iPS cell Research and Application in Kyoto University, where Prof. Yamanaka is the director. In this project, the goal is not only to construct a hardware platform that enables secure and easy data sharing between distantly-located institutions but also to set up software/procedures for promoting the conversion of their experimental data, including lab notes and Standard Operating Procedures, into electronic form to facilitate easier data sharing with higher security level; for protecting the intellectual property of data depositors; and for complying to the proper admission procedures issued by the Institutional Review Boards on ethical issues in dealing with clinical data. For example, we have started data sharing of various characteristics of Embryonic Stem cells that originated from the same source but had been cultivated in different institutions, trying to quantify the difference between them. In another example, we have examined the nature of some differentiated iPS cells that showed tendency of tumorigenesis using NGS technology, to find out its underlying cause. Undoubtedly, such efforts will be useful in improving the reliability of clinical applications in the field.

Opinion: The Way to Personalized Regenerative Medicine

As noted above, regenerative medicine is a highly promising field of research but it will take more than 10 years before being accepted in general practice, except for somatic cell-based therapy, which will soon become a routine in many hospitals. In this approach, cells derived from patients are typically applied to themselves. In this sense, it might be regarded as a form of personalized medicine, but the level of this therapy is still far from that of the personalized approach, as sketched above. This is partly due to the difficulty of an objective evaluation of the quality of applied cells, which are often not adequately purified, and partly because of the small amount of available data. Thus, in my opinion, to overcome these difficulties, we should explore to establish personalized medicine more specific to this field. In other words, we will need to collect as many clinical trial data/samples with their genomic information as possible, to characterize these samples with NGS as well as imaging technologies, and to exploit the use of various big-data-driven approaches, such as deep learning, for evaluating quality of patient-derived cells from the combination of multi-omics and image data. With this kind of approach, we will be able to improve safety and effectiveness of cell-based therapy, which still largely relies on empirical knowledge.

Concluding Remarks

In this article, I briefly outlined the recent notable activities on bioinformatics in Japan and introduced one of my current research projects as well as my opinion on a possibility of its advanced future. I confess that it was almost impossible for me to predict the current status of bioinformatics study in Japan 10 years ago and thus my present prediction may not come true. Nevertheless, I do hope that Japan will still continue to be one of the top runners in the study of both bioinformatics and regenerative medicine 10 years from now.


I thank Kuo-ching Liang and Asif M. Khan for critically reading the manuscript.

About the Author

Dr. Kenta Nakai is a professor at the Human Genome Center, the Institute of Medical Science, the University of Tokyo, Japan. He obtained his PhD degree in 1992 from Kyoto University and was the president of the Japanese Society for Bioinformatics in 2006 and 2007. His main research interest is to develop computational ways for interpreting biological information, especially that of transcriptional regulation. Two of his papers reporting the development of a knowledge-based prediction system of subcellular localization sites have been cited more than 1,100 times so far.


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