From FY2016 to FY2017, we provided technical support through next-17generation sequencing to researchers in and outside of RIKEN as a facil-ity named Genome Network Analysis Support (GeNAS). In FY 2018, we were reorganized into the Laboratory for Comprehensive Genomic Analysis (CGA) to start our own research activities, while still contributing the support of other researchers, as a part of the “IMS genome platform” activities.The objectives of our own research themes are to elucidate the molecular pathophysiology of human diseases, especially focusing on mitochondrial dis-eases, neurological diseases and other rare and intractable diseases, and to pro-vide the technological basis for medical therapeutics. We employ a multi-omics approach, with special emphasis on genome and transcriptome analyses. Spe-cifically, we focus on the identification and characterization of novel causative genes for these diseases. Using state-of-the-art sequencing technologies and sometimes developing our own proprietary methodologies, we have analyzed clinical cases in which it is difficult to reach a molecular diagnosis. During the last several years, we have identified at least 10 novel pathogenic variants and genes, including a repeat expansion diseaseWe are also addressing how the pathologic cells and molecules behave at tis-sue- and organ-level in relation to physiologically important pathways and key pathological phenomena. To this end, we have now started to conduct spatial transcriptome/proteome analysis of brains and other medically relevant tissues in human and animal models to determine how single-cell analysis-identified cell types are distributed within tissue architectures and what molecules reflect pathologic mechanisms.We are committed to other medically relevant themes as well. We are con-ducting single-cell analyses of the mammalian taste system to create a research platform that contributes to prevent lifestyle-related diseases. Epigenetic analy-ses (ChIP/ATAC/Methyl-seq) have clarified molecular mechanisms underlying the direct reprogramming of fibroblasts into another distinctively differentiated cell type, as a prelude to regenerative medicine for intractable diseases. A high-throughput screening system and optical visualization in zebrafish hearts are under development to discover new potential drug targets for the realization of personalized medicine.Figure: Future plansWe will continue to apply omics and functional analy-ses to mitochondrial and neurological diseases, taste receptors, direct reprogramming, and other themes in molecular medicine and biology. In addition, we will continue technological development for genomic and transcriptomic analyses. We continue to utilize state-of-the-art technologies such as Nanopore and PacBio long-read sequencers, as well as high quality short read sequencers, through the IMS genome platform, to solve biological/medical problems.Especially, because we recently are focusing on techno-logical development of single-cell technologies, we will apply these technologies to various important unan-swered questions in molecular medicine.Recent Major PublicationsOmichi N, Kishita Y, Nakama M, Sasai H, Terazawa A, Kobayashi E, Fushimi T, Sugiyama Y, Ichimoto K, Nitta KR, Yatsuka Y, Ohtake A, Murayama K, Okazaki Y. Novel ITPA variants identified by whole genome sequencing and RNA sequencing. J Hum Genet 68, 649-652 (2023)Moody J, Kouno T, Kojima K, Koya I, Leon J, Suzuki A, Hasegawa A, Akiyama T, Akiyama N, Amagai M, Chang JC, Fukushima-Nomura A, Handa M, Hino K, Hino M, Hirata T, Imai Y, Inoue K, Kawasaki H, Kimura T, Kinoshita T, Kubo K, Kunii Y, López-Redondo F, Manabe R, Miyai T, Morimoto S, Nagaoka A, Nakajima J, Noma S, Okazaki Y, Ozaki K, Saeki N, Sakai H, Seyama K, Shibayama Y, Sujino T, Tagami M, Takahashi H, Takao M, Takeshita M, Takiuchi T, Terao C, Yip CW, Yoshinaga S, Okano H, Yahamoto K, Kasukawa T, Ando Y, Carninci P, Shin JW, Hon CC. A single-cell atlas of transcribed cis-regulatory elements in the human genome. bioRxiv (2023)Yuuri Yasuoka, Tissue-specific expression of carbohydrate sulfotransferases drives keratan sulfate biosynthesis in the notochord and otic vesicles of Xenopus embryos. Front Cell Dev Biol 11, 957805 (2023)Invited presentationsOkazaki Y. “Impact of measuring heteroplasmy of a pathogenic mitochondrial DNA variant at the single-cell level in individuals with mitochondrial disease”Beijing Mitochondrial Workshop, (Beijing, China/Online) December 2023Okazaki Y. “Recent topics on genetic testing of mitochon-drial diseases” The 19th annual seminar of Japanese Society for Inherited Metabolic Diseases (Tokyo, Japan) July 2023Yasuoka Y. “Exploring the evolutionary process of vertebrates by developmental genomics” JT Biohistory Research Hall Seminar (Takatsuki, Japan) January 2023Laboratory for Comprehensive Genomic AnalysisTeam Leader: Yasushi Okazaki
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