Introduction

As the most pervasive marker present on mRNA and lncRNA, N6-methyladenosine (m6A) RNA methylation has been shown to participate in various biological processes. Recent studies revealed the distinct patterns of m6A methylome across human tissues, and a major challenge remains in elucidating the tissue-specific presence and circuitry of m6A methylation. We present here a comprehensive online platform m6A-TSHub for unveiling the context-specific m6A methylation and m6A-affecting mutations in 23 human tissues. m6A-TSHub consists of four core components, including:
1) m6A-TSDB: a comprehensive database of 184,554 and 499,369 m6A-containing peaks collected from 23 normal human tissues and 25 cancer samples, respectively. Among them, 17 out of 25 tumor samples have the m6A profiles of their matched primary tissues.
2) m6A-TSFinder: an integrated online server for the prediction of tissue-specific m6A modification in 23 human tissues, built upon a gated attention based multi-instance deep neural networks.
3) m6A-TSVar: a web server for systemically assessing the tissue-specific impact of genetic variants on m6A RNA modification in 23 human tissues.
4) m6A-CAVar: a database of 587,983 TCGA cancer mutations (derived from 27 cancer types) that may lead to the gain or loss of m6A sites in the corresponding cancer originating tissues.

m6A-TSDB

1. Click ‘m6A-TSDB’ under ‘Database’ category.

2. Click tissue of interest on the anatomy of human bodies (yellow circle) or text (red rectangle) to query tissue-specific m6A sites.

3. Filter the returned m6A sites by specifying the cancer cell line.

4. View specific m6A site in genome browser by clicking the `JBrowser’ button (scroll to the far right).

m6A-CAVar

1. Click ‘m6A-CAVar’ under ‘Database’ category

2. There are three ways to query somatic m6A-affecting variants:

1) Click tissue of interest on the anatomy of human bodies (yellow circle) or text (red rectangle) to query m6A-affecting mutations in that tissue.

- Users can retrieve m6A-affecting mutations that are specific to certain cancer type, gene type, leads to gain or loss of m6A sites, or with different confidence levels.

- Users can also filter the results by their annotations: whether is protein binding region, miRNA target site, splicing site or not, whether it has known diseases and phenotype linkage integrated from GWAS or ClinVar databases can also filter the results by their annotations: whether is protein binding region, miRNA target site, splicing site or not, whether it has known diseases and phenotype linkage integrated from GWAS or ClinVar databases.

2) Users can query the m6A-affecting mutations directly related to certain TCGA cancer type

3) Users can also enter genomic coordinates, gene name, COSMIC ID, Rs ID or disease annotation in search bar in the `Home` page to query mutation sites located on specific gene.

3. Click the `m6A-CAVar_ID` to view the detailed description of individual mutation site. RNA binding protein information, miRNA target, splicing, ClinVar and GWAS annotation will be shown if available.

4. View the mutation site in genome browser by clicking `JBrowser`.

m6A-TSFinder

1. Click ‘m6A-TSFinder’ under ‘Tool’ category.

2. Input query sequences (FASTA) to the box or upload FASTA file, specify parameters (Threshold, Tissue Model) and then click `submit`.

3. Results will be displayed when the job is completed (may take several minutes), users can click `Download` to download the results.

m6A-TSVar

1. Click ‘m6A-TSVar’ under ‘Tool’ category.

2. Input data (VCF) to the box or upload a VCF file, specify parameters (you may keep default values) and then click `submit`.

3. Results will be displayed when the job is completed (may take several minutes), users can click `Download` to download the results.

Data Download

Click the green `CSV` button to download m6A-associated genomic variants for different cancer type, tissue-specific m6A sites and cancer-related m6A sites.