GENCODE 2025: reference gene annotation for human and mouse

Area of Science:

• Genomics
• Transcriptomics
• Proteomics

Background:

• The GENCODE project provides comprehensive gene annotation for human and mouse genomes.
• The field of genomics is rapidly advancing with new technologies and methodologies.
• Accurate gene annotation is crucial for understanding genome function and disease.

Purpose of the Study:

• To detail the latest advancements in GENCODE's comprehensive gene annotation for human and mouse.
• To highlight the integration of new technologies for improved genomic and transcriptomic cataloging.
• To address challenges in resource usability and outline future directions in the pangenome era.

Main Methods:

• Long-read transcriptome sequencing for identifying novel transcripts and refining existing gene models.
• Integration of proteomics and Ribo-seq data to enhance annotation of translated sequences.
• Development of filtered genesets (e.g., MANE Select, GENCODE Primary) for improved usability.

Main Results:

• Significant expansion and reconfiguration of long non-coding RNA catalogs.
• Substantial improvements in existing transcript models and identification of numerous missing transcripts.
• Enhanced annotation of translated sequences through integrated multi-omics data.

Conclusions:

• GENCODE continues to evolve, leveraging cutting-edge technologies for increasingly granular genome annotation.
• New resources and filtered genesets enhance usability, addressing the complexity of comprehensive genomic data.
• The project is poised to contribute to the emerging pangenome era by propagating annotations across multiple genomes.