The 70th In Silico Megabank Research Seminar will be held on Friday, January 15, 2016. This Time, we will be welcoming Dr. Fumihiko Takeuchi, Research Institute, National Center for Global Health and Medicine as our lecturer, and he will be speaking on “Genome-wide Association Study (GWAS)”.

・Date/Time: January 15 (Friday) 5:00 pm‐6:30 pm
・Venue: Small Conference Room 2(3rd Floor), Tohoku Medical Megabank Building

・Title: Genome-wide Association Study (GWAS): Successful Increase in Scalability for Multi-ethnic Groups and Concerns about Area Difference
・Lecturer: Fumihiko Takeuchi（Research Institute, National Center for Global Health and Medicine）

＊This lecture is transferable as a class in the medical research-related lecture course.

・Abstract: With regard to bio-architecture shown as “DNA−RNA−Protein−Cell−Tissue−Organ−Individual Organism,” genome that DNA codes and diseases representing the health condition of individual organism position at both ends; however, genome study for human diseases is a potent approach to examine diseases and develop treatments. The reason for this possibility is that the relations between genomic variation and diseases can be statistically analyzed (association study) and statistical findings suggest their causal links. In this seminar, large-scale analysis on multi-ethnic groups that enhances the statistical power and area differences in genome which can be a cofounder in association study are introduced.
1. Large-scale GWAS on Blood Pressure
GWAS on blood pressure was conducted targeting Europeans and North Americans, East Asians, South Asians totaling 320,251 participants; 12 related genetic loci were newly identified. Many blood pressure-related SNPs were related to methylation of nearby CpG cites, which suggested that the genomic relations between SNPs and blood pressure are formed by way of methylation.
2. Area Differences in Genes among Japanese People
As an Asian variation project, 34 Asian populations including 8 Japanese populations totaling 3928 participants were analyzed. SNPs information of whole genome enabled categorization of Japanese populations into 9 clusters, and each cluster corresponded to certain areas in Japan. The impact of cluster must be examined as needed for disease association studies.

・Organizer: Yumi Yamaguchi, Masao Nagasaki

The 67th In Silico Megabank Research Seminar will be held on Friday, December 11.

This Time, we will be welcoming Dr. Kazuhiro Nakayama, Center for Molecular Medicine, Jichi Medical University as our lecturer, and he will be speaking on “Construction of Visceral Adipose Genome Bank and its Use”.

・Date/Time: December 11 (Friday) 5:00 pm‐6:30 pm
・Venue: Small Conference Room 2(3rd Floor), Tohoku Medical Megabank Building
・Title: Construction of Visceral Adipose Genome Bank and its Use
・Lecturer: Kazuhiro Nakayama（Center for Molecular Medicine, Jichi Medical University ）

＊This lecture is transferable as a class in the medical research-related lecture course.

・Abstract: Visceral adipose is white adipose tissue existing around peritoneum. Visceral adipose evokes various metabolic abnormalities such as hepatic dysfunctions, dyslipidemia, hypertension, hyperuricaemia, and impaired glucose tolerance by actively excreting free fatty acid and cytokine. The heritability of visceral obesity is partially independent from the heritability of subcutaneous fat accumulation; the identification of specifically-attributable genetic polymorphism hasn’t progressed very much yet. Understanding of the genetic background of visceral fat accumulation may contribute to pathophysiological analysis of various chronic diseases that are lead by it. Our group collected genomic DNA and the result data of various health check items such as visceral fat area of periumbilical region, serum lipid level, and existence of fatty liver from 3013 adults who had general multiphasic health screening at Jichi Medical University Hospital and then constructed visceral adipose genome bank. In this seminar, the relationship between Tribbles Pseudokinase family gene and lifestyle diseases which were revealed from the analysis of this genome bank and outcomes so far found are introduced.

・Organizer: Kazuharu Misawa, Masao Nagasaki

The 66th In Silico Megabank Research Seminar will be held on Tuesday, December 8. This Time, we will be welcoming Dr. Wojciech Makalowski, University of Muenster as our lecturer, and he will be speaking on “Nanopore Sequencing for Genotyping Pathogens of Tropical Diseases”.

・Date/Time: December 8(Tuesday) 5:00 pm‐6:30 pm
・Venue: Small Conference Room 2(3rd Floor), Tohoku Medical Megabank Building
・Title: Nanopore Sequencing for Genotyping Pathogens of Tropical Diseases – Bioinformatics Challenges
・Lecturer: Wojciech Makalowski（Institute of Bioinformatics, University of Muenster）

＊This lecture is transferable as a class in the medical research-related lecture course.

・Abstract: Sequencing technology continues to revolutionize life sciences. However, all the main stream technologies share several weaknesses, such as short reads and bulky instruments with high price tag. The latter prohibits usage of the sequencing directly in the field or in rural hospitals. Therefore there’s a pressing need for a simple and low-cost instrument that could be used for rapid disease diagnosis or biological sample identification. Recently introduced MinIONTM by Oxford Nanopore Technologies meets these expectations as it’s very portable with just four inches in length and operability via the USB port of a laptop computer. As a part of the Oxford Nanopore MinIONTM Access Program (MAP) we have tested applicability of the nanopore technology for genotyping of tropical diseases. In particular, it was applied to two different tasks: serotype determination of the dengue virus and genotyping of the malaria parasites. Despite very low accuracy of a single molecule read we were able successfully discriminate between different dengue virus serotypes using multiple-sequence alignment and majority rule for the base call. We demonstrate that sequence depth generated by a single run of the MinIONTM is sufficient for precise serotyping of the virus. Similarly, our preliminary results suggest that the nanopore sequencing should be useful in genotyping of the malaria parasite. Since Oxford Nanopore Technologies don’t provide any specialized software for the sequence analysis, we built a simple web-based pipeline for sero- and genotyping. The pipeline is freely available at http://bioinformatics.uni-muenster.de/tools/NanoPipe/index.hbi.

・Organizer: Yumi Yamaguchi, Masao Nagasaki

The 65th In Silico Megabank Research Seminar will be held on Friday, November 27. This Time, we will be welcoming Dr. Toshimichi Yamamoto, Nagoya University Graduate School of Medicine as our lecturer, and he will be speaking on “Genetic Relationship of Human Population Viewing from Microsatellite on Autosomes and Y Chromosomes”.

・Date/Time: November 27 (Friday) 5:00 pm‐6:30 pm
・Venue: Small Conference Room 2(3rd Floor), Tohoku Medical Megabank Building
・Title: Genetic Relationship of Human Population Viewing from Microsatellite on Autosomes and Y Chromosomes – Mainly for Human Population in Japan and Nearly Countries –
・Lecturer: Toshimichi Yamamoto (Department of Legal Medicine and Bioethics, Nagoya University Graduate School of Medicine)

＊This lecture is transferable as a class in the medical research-related lecture course.

・Abstract: Until now, various genetic researches on human population have been conducted using about 1M-long genome-wide SNPs analysis and whole genome sequence analysis. At the same time, in the field of Forensics, in order for individual identification and blood relationship, microsatellite (in forensics called STRs: short tandem repeats) is commercialized as a multiplex kit which enables grouping of over dozen loci and now universally used. With such data, it is possible to extrapolate ancestral human population of each individual to some extent. However, it is difficult to extrapolate ancestral line of relatively genetically-related human population in Japan and near countries. In this speech, using 105 STR loci data, genetic relationship of human populations in East and Southeast Asia and the possibility of statistical discrimination between Japanese and Chinese or Japanese and Korean are introduced.  In addition, Y-STRs have significance in the field of Forensics to test sexual offense and agnate blood relationship; commercialized kits are also widely used similar to autosomes. The result of Y-STRs haplotype network analysis using this kit on 5 areas of Mongol and that on ethnic minorities collaboratively conducted with RIKEN BRC are also introduced.

・Organizer: Yosuke Kawai, Masao Nagasaki

The 64th In Silico Megabank Research Seminar will be held on Tuesday, November 24. This Time, we will be welcoming Dr. Yasuhiro Go, Center for Novel Science Initiatives, National Institutes of Natural Sciences as our lecturer, and he will be speaking on “Understand ourselves through genome -What separates humans and apes-“.

・Date/Time: November 24 (Tuesday) 4:00 pm‐5:30 pm
・Venue: Small Conference Room 2(3rd Floor), Tohoku Medical Megabank Building 

・Title: Understand ourselves through genome  -What separates humans and –
・Lecturer: Yasuhiro Go (Center for Novel Science Initiatives, National Institutes of Natural Sciences)

＊This lecture is transferable as a class in the medical research-related lecture course.

・Abstract: It has been about 15 years since the reference genome sequence of the humans was decoded. During this time phrase, whole genome analysis of 100,000 people and studies on single cell genomics & transcriptomics have been conducted worldwide in order to analyze the genes causing human diseases and to study variations. However, no matter how much various human genomes are revealed, in addition to human genome,  comparison of the characteristics and variations of other species with those of human is inevitable for fundamental understanding of humans and, further, acknowledging the evolutional meaning. Hence, with using disease and evolution as the keywords, I have conducted research mainly on the genome variation analysis of primates other than humans, especially chimpanzees, macaques, and marmosets, as the comparison targets with humans, and on transcriptome analysis of their brains. In this seminar, “what is between humans and apes” based on the genomics and transcriptomics of primates other than humans is considered.

・Organizer: Yukuto Sato, Masao Nagasaki

The 4th inter-disciplinary area Seminar will be held on Thursday, September 17.

・Date: Thursday, September 17, 2015
・Time: 6:00 pm ‐ 8:00 pm
・Venue : Tohoku University Graduate School of Medicine
・Title: Genomic medicine based on Information science
・Lecturer : Prof. Masao Nagasaki

The 62nd In Silico Megabank Research Seminar will be held on Friday, August 21.  This Time, we will be welcoming Dr. Ashwini Patil, Institute of Medical Science, The University of Tokyo as our lecturer, and she will be speaking on identifying active gene sub-networks from time-course gene expression profiles using a network analysis method.

・Date: Friday, August 21, 2015
・Time: 5:00 pm ‐ 6:30 pm
・Venue : Small Conference Room 2(3rd Floor), Tohoku Medical Megabank Building
・Title: Identifying active gene sub-networks from time-course gene expression profiles using a network analysis method
・Lecturer : Ashwini Patil (The Institute of Medical Science, The University of Tokyo )

＊This lecture is transferable as a class in the medical research-related lecture course.

・Abstract : Time-course gene expression profiles are frequently used to study cellular response to stimulus and to infer molecular pathways involved in cellular response. I will introduce a method to identify active gene sub-networks with temporal paths using time-course gene expression profiles in the context of a weighted gene regulatory and protein-protein interaction network. The method uses a specialized form of the network flow optimization approach to identify the most probable paths connecting the genes with significant changes in expression at consecutive time intervals.  We used this method to identify response pathways in the innate immune response using time course gene expression profiles of activated immune cells1 as well as the yeast osmotic stress response2. Using this method, we are now comparing the regulatory networks responsible for the distinct immune outcomes produced from different pathogens. Using these response networks, we would like to identify unique regulatory genes associated with each pathogenic component to help better understand the ways in which the immune response differs for distinct pathogens.

・Organizer : Masao Nagasaki

A research group at Tohoku Medical Megabank Organization (ToMMo) has successfully developed the Japonica Array^TM which is the first ever SNP array optimized for Japanese population.
The aim of development of Japonica Array^TM is not only to facilitate the prospective genomic cohort study conducted by ToMMo but also to make a contribution to the genomic medicine studies in Japan.

The array contains 659,253 SNPs, including tag SNPs for imputation, SNPs of Y chromosome and mitochondria, and SNPs related to previously reported genome-wide association studies and pharmacogenomics. The Japonica Array^TM provides better imputation performance for Japanese individuals than the existing commercially available SNP arrays with both the 1KJPN^* panel and 1KGP panel (the International 1,000 genomes project).

*1KJPN：ToMMo constructed the reference panel, which contains 2,100 million single nucleotide polymorphisms (SNPs), from whole-genome sequence data of 1,070 Japanese individuals.

Article
Yosuke Kawai, Takahiro Mimori, Kaname Kojima, Naoki Nariai, Inaho Danjoh, Rumiko Saito, Jun Yasuda, Masayuki Yamamoto, Masao Nagasaki
“Japonica array: Improved genotype imputation by designing a population-specific SNP array with 1,070 Japanese individuals”
Journal of Human Genetics advance online publication, 25 June 2015; doi:10.1038/jhg.2015.68

The genotyping service of the Japonica Array^TM is now provided by Toshiba Healthcare Company under the license from Tohoku University.
You can download the SNP list designed on Japonica Array^TM from this website.
http://nagasakilab.csml.org/en/japonica

The 61st In Silico Megabank Research Seminar will be held on Thursday, April 16 . This Time, we will be welcoming Dr. Ichizo Kobayashi, Graduate School of Frontier Sciences, The University of Tokyo as our lecturer, and he will be speaking on “Epigenetics-driven Evolution: Demonstration through OMICS Comparison of Multiple Sequences within Bacterial Species.”

・Date: Thursday, April 16, 2015
・Time: 10:00 am‐11:00 am
・Venue : Small Conference Room 2(3rd Floor), Tohoku Medical Megabank Building
・Title: Epigenetics-driven Evolution: Demonstration through OMICS Comparison of Multiple Sequences within Bacterial Species
・Lecturer : Ichizo Kobayashi (Graduate School of Frontier Sciences, The University of Tokyo)

＊This lecture is transferable as a class in the medical research-related lecture course.

・Abstract : Concerning the adaptive evolution, a theory on the unit of evolution based on “epigenetic state” was developed in contrast to the idea of “selection from various genomic sequencing.” The epigenetic state was demonstrated in the study with bacteria that can directly pass on to the next generation.  Many of DNA methylase of bacteria create restriction-modification system and restriction enzyme recognizes the same sequence. They are “selfish” epigenetics that destroy non-self epigenomes. Excluding cells from which restriction-modification system is excluded through chromosomal breaks forces host bacteria into the certain methylome. In our study, it was demonstrated that the restriction-modification system modulates the recognition sequence, alter the creation of methylome in various ways, and leads changes in the patterns of gene expressions and various phenotypes.  Restriction of these restriction-modification systems from internal and external environment, a type of restriction enzyme that cuts bases out as is the case in demethylating enzyme of eukaryote, and degradation and alteration of rRNA genes used for metagenome analysis are also introduced; we would like to discuss the perception of microevolution of microbiome

・Organizer : Yoko Kuroki, Masao Nagasaki

The 59th In Silico Megabank Research Seminar will be held on Friday, March 13. This Time, we will be welcoming Dr. Shuhei Mano, The Institute of Statistical Mathematics as our lecturer, and he will be speaking on “Approximate Bayesian Computation and its Relevant Fields”.

・Date: Friday, March 13, 2015
・Time: 5:00 pm‐6:30 pm
・Venue: Small Conference Room 2(3rd Floor), Tohoku Medical Megabank Building
・Title: Approximate Bayesian Computation and its Relevant Fields
・Lecturer: Shuhei Mano（The Institute of Statistical Mathematics）

＊This lecture is transferable as a class in the medical research-related lecture course.

・Abstract: Even though it involves numerical aspects only, Baysian data analysis is difficult to be performed with precision as it is based on complex models. Especially at the time of handling large-scale data, researchers must face the limits of computer performance.  Like the analysis of outliers, the descriptive approach is one way to analyze data as it has an advantage in the utilization the scale of data; however, there is an issue that all predictions are based on models. Approximate Bayesian Computation is a method of Baysian data analysis which allows the maximal precision within the computable domain with simulation although it does not provide clear likelihood of the models. Despite the fact that it is based on models, the structure of summary statistics is made algorithmically. Thus, the integration of data modeling and machine learning gives spice to the methodology. In this seminar, the background, the theoretical base and method, and possible application to actual problems are introduced.

・Organizer: Yosuke Kawai, Masao Nagasaki