CanASM: A comprehensive database for genome-wide allele-specific DNA methylation identification and annotation in cancer
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Allele-specific DNA methylation (ASM) provides critical insights into the complex genetic and epigenetic mechanisms regulating gene transcription. Emerging evidence suggests that ASM is particularly enriched in gene enhancer regions, and recent studies have demonstrated that ASM is increased in cancer tissues compared with normal tissues. Despite the increasing recognition of ASM as a potential biomarker in tumorigenesis, systematic resources dedicated to identifying and annotating ASMs in cancer contexts remain limited. In this study, we developed CanASM ( https://bioinfor.nefu.edu.cn/CanASM/ ), the first comprehensive database specifically designed to identify and annotate ASM in cancer. In CanASM, ASM sites identified from bisulfite sequencing data across 31 cancer types and their matched normal tissue samples are cataloged. Importantly, CanASM includes extensive regulatory annotations for ASMs, including associated genes, cis-regulatory elements and transcription factor binding colocalizations, transcription factor affinity changes, etc. Users can query and explore ASMs using various parameters, such as single-nucleotide variations (SNVs), chromosomal coordinates, and gene names. The current version of CanASM includes 5,003,877 unique SNV–CpG pairs, including 3,056,776 index SNVs, of which 2,634,406 are single-nucleotide polymorphisms (SNPs), and 4,157,508 CpGs. With an intuitive interface for browsing, querying, analyzing, and downloading, CanASM serves as a valuable resource for researchers investigating cancer-associated genetic variations and epigenetic regulation in cancer.
Author summary
Identifying target genes and regulatory mechanisms of cancer-associated genetic variants remains a major challenge in the post-GWAS era. Existing databases like Pancan-meQTL and ASMdb have contributed to uncovering the role of genetic variants in cancer by linking DNA variations to methylation. However, they lack comprehensive regulatory annotations for such sites and rely solely on genomic proximity for target gene prediction, overlooking distal interactions. Our analysis using 3D interaction data reveals that over 94.8% of ASMs exhibit distal regulatory relationships, emphasizing their critical role in cancer epigenetics. Furthermore, these databases cover a limited number of cancer types (Pancan-meQTL: 23, ASMdb: 8). To address these limitations, we developed CanASM, a database that provides ASMs identified from BS-seq data for 31 human cancers, along with multidimensional regulatory annotations for ASM sites. This includes target genes, cis-regulatory elements (enhancers, ATAC-seq regions, insulators, 3D interactions, CpG islands), TFBSs, and GWAS cancer trait associations. Additionally, CanASM offers three interactive tools for analyzing TF binding affinity changes, predicting ASM target genes through 3D interactions, and identifying cell marker variations. As a comprehensive resource for SNV-driven epigenetic regulation in cancer, CanASM is helpful for in-depth research in cancer genetics and epigenetics.
