The Laboratory of Applied Computational Genomics analyzes omics data 14to understand the molecular basis of cellular functioning.In basic genomics, using Hi-C chromosome conformation capture sequenc-ing data across 18 cell types and tissues, we associated cell type-specific func-tional categories with lncRNAs based on their physical association with protein-coding genes. RNA-chromatin interaction data confirmed that lncRNAs bind to the target genes identified by Hi-C and, together with RNA-protein interaction data, suggested that lncRNAs act as scaffolds to gather regulatory proteins and to guide them to their target genomic sites (Agrawal et al., 2024). Our function-al annotations of lncRNAs are provided to the community through ZENBU-Reports (https://fantom.gsc.riken.jp/zenbu/reports), a web application to create interactive scientific web portals as an alternative to traditional static forms of data dissemination and visualization (Severin et al., 2023).In biomedicine, we collaborate closely with the IMS Laboratory for Human Disease Models in the analysis of Cap Analysis of Gene Expression (CAGE) data of leukemia patients for personalized medicine, focusing on the activation of promoters and enhancers depending on the complex karyotype and muta-tions in each patient. Together with multiple IMS laboratories, we study the transcriptome and chromatin conformation of human airway epithelial cells in response to infection by different strains of SARS-CoV-2 or influenza virus.Complementary to sequencing data analysis, we perform electron micro-scope imaging to visualize chromatin and regulatory molecules in the nucleus to uncover the biophysical reality underlying gene regulation. Using antibodies and in-situ hybridization probes with attached nanogold beads that are visible in the electron microscope, we label specific RNAs, their genomic site of origin, histone marks, and RNA Polymerase II, aiming to create a 3D model of the local regulatory environment. The development of automated image analysis methods is crucial for the interpretation of the images.Figure: Electron microscope image of MCF-10A human mam-mary epithelial cells in which RNA Polymerase II is labeled by nanogold beads, observable as black dots in the image.Recent Major PublicationsAgrawal S, Buyan A, Severin J, Koido M, Alam T, Abuges-saisa I, Chang HY, Dostie J, Itoh M, Kere J, Kondo N, Li Y, Makeev VJ, Mendez M, Okazaki Y, Ramilowski JA, Sigorskikh AI, Strug LJ, Yagi K, Yasuzawa K, Yip CW, Hon CC, Hoffman MM, Terao C, Kulakovskiy IV, Kasukawa T, Shin JW, Carninci P, De Hoon MJL. Annotation of nuclear lncRNAs based on chromatin interactions. PLoS One 19, e0295971 (2024)Severin J, Agrawal S, Ramilowski JA, Deviatiiarov R, Shin JW, Carninci P, De Hoon M. ZENBU-Reports: a graphical web-portal builder for interactive visualization and dissemination of genome-scale data. NAR Genom Bio-inform 5, lqad075 (2023)De Hoon M, Bonetti A, Plessy C, Ando Y, Hon CC, Ishizu Y, Itoh M, Kato S, Lin D, Maekawa S, Murata M, Nishiyori H, Shin JW, Stolte J, Suzuki AM, Tagami M, Takahashi H, Thongjuea S, Forrest ARR, Hayashizaki Y, Kere J, Carninci P. Deep sequencing of short capped RNAs reveals novel families of noncoding RNAs. Genome Res 32, 1727-1735 (2022)Invited presentationsDe Hoon M. “Functional genomics and its application in biomedicine” Departmental seminar, McGill Genome Center, McGill University (Montreal, Canada) May 2023De Hoon M. “Functional genomics and its application in biomedicine” Departmental seminar, The Jackson Labo-ratory (Farmington, United States) May 2023Agrawal S. “Role of chromatin 3D organization in regu-lating genome functionality” Computational and Sys-tems pathology seminar series, Weill Cornell Medicine (New York, United States) May 2023De Hoon M. “Functional genomics for disease applica-tions” Special Seminar, Princess Margaret Cancer Centre (Toronto, Canada) March 2023De Hoon M. “Functional genomics for disease applica-tions” Computational and Systems pathology seminar series, Weill Cornell Medicine (New York, United States) March 2023Laboratory for Applied Computational GenomicsTeam Leader: Michiel de Hoon
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