Our mission is to understand the roles of the non-coding genome in 13A)B)Figure: Ethnic-specific and cell-type specific tCRE activities at an intergenic hyperactive locusA) An example of an intergenic hyperactive distal locus with clusters of highly active distal tCREs, defined by the transcription start site (TSS) signal, in peripheral blood mononuclear cells of Japanese and Korean populations. B) A UMAP showing the C)human diseases in terms of dysregulation of gene expression through integration of transcriptomic, epigenomic and genetic data. Expression of genes is primarily controlled by the activities of their cognate cis-regulatory elements (CREs, mostly promoters and enhancers), and our team focuses on analyzing their activities in various cell-type-specific and disease-specific contexts on a population level scale using single cell technologies. These contexts include variations of CRE activities in immune cells across Asian populations, dysregu-lation of gene regulatory networks in hematopoietic stem cells in Acute My-eloid Leukemia and disease-specific responses in iPSC-derived motor neurons in Amyotrophic Lateral Sclerosis. We use single-cell RNA-5’end-sequencing to profile the activities of transcribed CREs (tCREs) in these systems, enabling us to interrogate the context-specific activities of distal tCREs, which are crucial in gene regulation (Figure). We also develop tools for identification of authentic tCREs from these data (https://github.com/chung-lab/SCAFE) and adopt deep learning methods to predict the effects of genetic variants on gene expression using these data. Our ultimate goal is to integrate these context specific CRE activities with the genetic data to pinpoint the crucial genetic variants contrib-uting to predisposition to disease.Recent Major PublicationsWoogeng IN, Kaczkowski B, Abugessaisa I, Hu H, Tachibana A, Sahara Y, Hon CC, Hasegawa A, Sakai N, Nishida M, Sanyal H, Sho J, Kajita K, Kasukawa T, Takasa-to M, Carninci P, Maeda A, Mandai M, Arner E, Takahashi M, Kime C. Inducing human retinal pigment epithelium-like cells from somatic tissue. Stem Cell Reports 17, 289-306 (2022)Syed KM, Hon CC. Heterogeneity among enhancer RNAs: origins, consequences and perspectives. Essays Bio-chem 65, 709-721 (2021)Sun M, Wang Y, Zheng C, Wei Y, Hou J, Zhang P, He W, Lv X, Ding Y, Liang H, Hon CC, Chen X, Xu H, Chen Y. Systematic functional interrogation of human pseudogenes using CRISPRi. Genome Biol 22, 240 (2021)peripheral blood mononuclear cells collected from Japanese and Korean populations. C) The expression levels of the hyperactive distal locus among Japanese and Korean single-cells (top) and individuals (bottom).Laboratory for Genome Information AnalysisTeam Leader: Chung-Chau Hon
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