CTQuantity, splicing patterns and stability(A) RNA-sequencing(A) RNA-sequencing: expression QTL (eQTL): expression QTL (eQTL))LnToQitha(c iLfiTdQom e neontostihsi H:or (C(BATOD)AAp HDOCT-ASp-HeQCen chQnST-T L-cLshmeroqmuaenn qauen nscitatcnsuitnagtusgs) : : gnicneuqes-PIhC )D(titi: DNA methylation QTL (meQTL)(F) Bisulfite-sequencing: Transcription factor binding QTL ion factor binding DNA methylationquencing(E) ChIP-sequencing)TF binding sitesquE) ChIP-seq nscriptioptio)(bQTL) ssee67sion to define the genomes of 25,000 primary untreated cancers (the 25K Initiative) in 2018. The ICGC solved numerous data governance, ethical and logistical challenges to make global genomic data sharing for cancer a reality, providing the interna-tional community with comprehensive genomic data for many cancer types. As the second ICGC initiative, the ICGC launched a “Pan-Cancer” Whole Genome project (PCAWG) in 2014, in which WGS data together with RNA-Seq of 2834 samples were analyzed in uniform pipelines within the same computational environment and cloud computing. RIKEN has been contributing to this project as a member of a technical working group and as PI/researchers in working groups for several projects. In February 2020, PCAWG published more than 20 papers in Nature and Na-genome wide association study (GWAS). Germline genet-ic variations provide us with evidence into the causal relationship of an observed phenomenon and its pathogenesis. In this regard, the majority of GWAS risk variants have been reported to locate in the non-coding regions on the chromosome and function as an expression-quantitative trait locus (e-QTL), regulating the expression levels of genes. Therefore, by integrating genomic in-formation, qualitative and quantitative analyses of transcriptomes together with cell-specific epigenomes, we will better understand the causal pathogenic components of immune cells in various immune-mediated diseases.IMS is now setting up a system to identify various subtypes of leukocytes from peripheral blood mononuclear cells (PBMC) of heathy individuals. The aim of this project is to obtain the utmost unbiased relationship between genotypes and gene ex-pression from healthy donors. Cell separation is performed by fluorescence-activated cell sorting into about 30 different subsets. Cells are then analyzed in the steady state or in further stimulated conditions, such as with combinations of cytokines and cell sur-face receptor agonists to capture the dynamic responses of gene regulation. Firstly, genotyping as well as RNA-seq are performed. With this data, we will obtain eQTL as well as splicing QTL in-ture sister journals and wrapped up. The RIKEN group has been focusing on mitochondria genome (mtDNA) mutations in cancer WGS data and found instances of somatic transfer of mitochon-drial DNA into the cancer nuclear genome. They also observed excessive accumulation of high-allele-frequency truncating muta-tions in mtDNA, specifically in kidney cancers.formation. Cap analysis of gene expression (CAGE), assay for transposase-accessible chromatin using sequencing (ATAC-seq), and several histone mark analyses for each subset are powerful tools to be used for identifying the causal relationship between genetic variation and gene expression.Figure: A Circos plot representing somatic mtDNA nuclear transfer events in a bladder cancer genome. Human chromosomes and mtDNA (MT) are shown in the outer layer. Chro-mosomal rearrangements are shown as gray curves and mtDNA nuclear transfers are represented by red curves.Figure: Integration of genetic information into immune functions: The eQTL projectGCAAEnhancer(H) Captured HiC-sequencing/MicroC-sequencingDNA methylationH3K4me3Polymerase ⅡRNAH3K9acH3K4me1TranscriptionfactorsPromoter(G) CAGE-sequencing:Promoter usage QTL (puQTL)H3K27acDNase IH3K27me3Tn5E-lncRNAE-lncRNA(G) CAGE-sequencing:Enhancer activity QTL (eaQTL)Genetic variantsGeneCoding RNACdiP-lncRNAInternational Cancer Genome Consortium (ICGC) and PCAWG projectThe ICGC was established in 2007 and concluded its mis-eQTL project: Integration of genetic information into immune functionsMany disease susceptibility variants have been identified by
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