M6ADD: a comprehensive database of m⁶A modifications in diseases

Area of Science:

• Epigenetics and Molecular Biology
• Computational Biology and Bioinformatics
• Genomics and Disease Research

Background:

• N6-methyladenosine (m⁶A) is a crucial epitranscriptomic modification regulating gene expression and implicated in various diseases, notably cancers.
• Understanding m⁶A-disease associations is vital for developing novel therapeutic strategies.
• Existing resources lack comprehensive, integrated data on m⁶A modifications and their links to human diseases.

Purpose of the Study:

• To establish a public, web-based database, M6ADD (m⁶A-diseases database), for curated and predicted m⁶A-disease associations.
• To provide researchers with a comprehensive tool for querying, analyzing, and exploring m⁶A modification data.
• To facilitate the investigation of the functional roles of m⁶A modifications in gene disorders and diseases.

Main Methods:

• Manual curation of over 2000 publications to identify experimentally confirmed m⁶A-disease associations.
• Application of computational and statistical methods to analyze 30 high-throughput sequencing datasets for predicted m⁶A-disease associations.
• Network analysis prediction methods to identify potential m⁶A regulatory proteins in 24 cancers.
• Development of a tool for exploring m⁶A-modified gene functions via protein-protein interaction networks.

Main Results:

• The M6ADD database contains 222 experimentally validated m⁶A-disease associations across 59 diseases.
• An additional 409,229 m⁶A-disease associations were computationally predicted from 30 high-throughput sequencing datasets.
• Data on 5,239 potential m⁶A regulatory proteins linked to 24 cancers are included.
• A functional exploration tool based on protein-protein interaction networks is available.

Conclusions:

• M6ADD serves as a valuable, publicly accessible resource for m⁶A-disease association research.
• The database integrates experimental and computational findings, offering a broad perspective on m⁶A's role in disease.
• M6ADD supports the exploration of m⁶A modifications as potential therapeutic targets for various diseases, including cancers.