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Targeted RNA Sequencing Assay to Characterize Gene Expression and Genomic Alterations

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GENCODE: massively expanding the lncRNA catalog through capture long-read RNA sequencing.

Gazaldeep Kaur¹, Tamara Perteghella^1,2, Sílvia Carbonell-Sala¹

¹Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona 08003, Catalonia, Spain.

Biorxiv : the Preprint Server for Biology

|November 18, 2024

Summary

The GENCODE consortium significantly expanded long non-coding RNA (lncRNA) annotations in human and mouse genomes. This comprehensive update enhances understanding of gene function and disease associations.

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Area of Science:

Genomics
Molecular Biology
Bioinformatics

Background:

Accurate gene annotations are crucial for understanding genome function.
Existing long non-coding RNA (lncRNA) catalogs are incomplete and fragmented.
The GENCODE consortium provides foundational human and mouse genome annotations.

Purpose of the Study:

To conduct the most comprehensive annotation of long non-coding RNAs (lncRNAs) to date.
To improve the functional interpretability of the human and mouse genomes.
To establish human-mouse orthologs for lncRNAs, particularly those linked to disease.

Main Methods:

Manual annotation of full-length long-read sequencing data.
Analysis of matched embryonic and adult tissues from human and mouse.
Targeted sequencing of orthologous genomic regions.

Main Results:

Added 17,931 novel human genes and 22,784 novel mouse genes to the GENCODE catalog.
Represented a 2-fold increase in human and 6-fold increase in mouse lncRNA transcripts.
Established human-mouse orthologs for disease-associated lncRNAs at three times the previous rate.
Novel lncRNA annotations exhibit evolutionary constraints and link to phenotype-associated variants.
Explained millions of previously unassigned "orphan" omics measurements.

Conclusions:

The expanded GENCODE lncRNA annotations are a critical advancement for deciphering human and mouse genomes.
This work significantly enhances the functional interpretability of genomic data.
The improved ortholog assignments facilitate cross-species research in lncRNA function and disease.