Journal: medRxiv

Article Title: Mapping chromatin interactions at melanoma susceptibility loci and cell-type specific dataset integration uncovers distant gene targets of cis -regulation

doi: 10.1101/2024.11.14.24317204

Figure Lengend Snippet: (A) Summary of fine-mapped variants overlap with chromatin interaction cis -regulatory regions in the ATAC-seq and ChromHMM datasets. (B) Stacked bar plot summary of fine-mapped variants (CCVs) and nominated target genes (CCGs) after integrating the chromatin interaction dataset with melanocyte- and melanoma-specific ATAC-seq, ChromHMM, and MPRA datasets for each of 68 melanoma risk signals. The top bar plot shows the total number of fine-mapped variants that are linked to at least one target gene using the chromatin interaction dataset, while blue color shows the number of interacting variants overlapping a potential regulatory region in any of the ATAC-seq or ChromHMM datasets and the variant is also FDR significant in MPRA dataset. The bottom plot shows the number of unique genes nominated as potential candidates using chromatin interaction data only, while the green color shows the number of candidate genes following integration with epigenomic (ATAC-seq and ChromHMM) and MPRA datasets.

Article Snippet: Specifically: Melanocyte-specific active promoter regions : We annotated genomic regions as melanocyte-specific active promoters using the NIH Roadmap Epigenomics Mapping Consortium ChromHMM imputed state model annotations , derived from human primary neonatal melanocyte cultures (imputed ChromHMM state model data was downloaded from the UCSC genome browser Roadmap Epigenomics Integrative Analysis Hub for melanocyte samples E059, E061).

Techniques: Variant Assay

Journal: medRxiv

Article Title: Mapping chromatin interactions at melanoma susceptibility loci and cell-type specific dataset integration uncovers distant gene targets of cis -regulation

doi: 10.1101/2024.11.14.24317204

Figure Lengend Snippet: eQTL/TWAS CCGs were nominated when colocalization of eQTL and GWAS data was observed, or alternatively when the gene was identified as FDR-significant via Transcriptome Wide Association Study (TWAS), using either primary melanocyte or melanoma tumor eQTL reference datasets. Likewise, meQTL/MWAS CCGs were nominated via meQTL colocalization or an FDR-significant Methylome-Wide Association Study finding, where the significant CpG probe was located within a gene promoter or gene body, and meQTL reference datasets from melanocytes and melanoma tumors were tested separately. High confidence CCGs were nominated via integration analyses of fine-mapping, chromatin interactions datasets with epigenomic (ATAC-seq and ChromHMM) and MPRA data derived from melanocytes and melanoma cells.

Article Snippet: Specifically: Melanocyte-specific active promoter regions : We annotated genomic regions as melanocyte-specific active promoters using the NIH Roadmap Epigenomics Mapping Consortium ChromHMM imputed state model annotations , derived from human primary neonatal melanocyte cultures (imputed ChromHMM state model data was downloaded from the UCSC genome browser Roadmap Epigenomics Integrative Analysis Hub for melanocyte samples E059, E061).

Techniques: Derivative Assay

Journal: medRxiv

Article Title: Mapping chromatin interactions at melanoma susceptibility loci and cell-type specific dataset integration uncovers distant gene targets of cis -regulation

doi: 10.1101/2024.11.14.24317204

Figure Lengend Snippet: Figure shows data from melanocyte DNase I hypersensitivity sequencing (Roadmap, n=2 melanocyte cultures), melanocyte ChromHMM (Roadmap, n=2 melanocyte cultures), melanocyte ATAC-seq (n=5 cultures), and melanoma cell ATAC-seq relative to genes in the region. Fine-mapped variants for both loci and location of capture-HiC baits is shown along with chromatin looping. Fine-mapped variants from both loci located within the CDKAL1 gene and near HDGFL1 , respectively, directly interact with the SOX4 promoter region.

Article Snippet: Specifically: Melanocyte-specific active promoter regions : We annotated genomic regions as melanocyte-specific active promoters using the NIH Roadmap Epigenomics Mapping Consortium ChromHMM imputed state model annotations , derived from human primary neonatal melanocyte cultures (imputed ChromHMM state model data was downloaded from the UCSC genome browser Roadmap Epigenomics Integrative Analysis Hub for melanocyte samples E059, E061).

Techniques: Sequencing