A joint NCBI and EMBL-EBI transcript set for clinical genomics and research

By Joannella Morales, S. Pujar, J. Loveland, Alex Astashyn, Ruth Bennett, Andrew E. Berry, Eric Cox, C. Davidson, O. Ermolaeva, C. Farrell and 30 more. Nature, 2022

465 citations recorded by the source corpus.

Comprehensive genome annotation is essential to understand the impact of clinically relevant variants. However, the absence of a standard for clinical reporting and browser display complicates the process of consistent interpretation and reporting. To address these challenges, Ensembl/GENCODE1 and RefSeq2 launched a joint initiative, the Matched Annotation from NCBI and EMBL-EBI (MANE) collaboration, to converge on human gene and transcript annotation and to jointly define a high-value set of transcripts and corresponding proteins. Here, we describe the MANE transcript sets for use as universal standards for variant reporting and browser display. The MANE Select set identifies a representative transcript for each human protein-coding gene, whereas the MANE Plus Clinical set provides additional transcripts at loci where the Select transcripts alone are not sufficient to report all currently known clinical variants. Each MANE transcript represents an exact match between the exonic sequences of an Ensembl/GENCODE transcript and its counterpart in RefSeq such that the identifiers can be used synonymously. We have now released MANE Select transcripts for 97% of human protein-coding genes, including all American College of Medical Genetics and Genomics Secondary Findings list v3.0 (ref. 3) genes. MANE transcripts are accessible from major genome browsers and key resources. Widespread adoption of these transcript sets will increase the consistency of reporting, facilitate the exchange of data regardless of the annotation source and help to streamline clinical interpretation. Matched Annotation from NCBI and EMBL-EBI (MANE) delivers joint transcript sets from Ensembl/GENCODE and RefSeq for standardizing variant reporting in clinical genomics and research.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/df2ab6f41bd9cb1b224461b50bad7c7dee2cdfe5

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

In Molecular Biology

Citations in the corpus

Ensembl 2023 (2022, methodology): “We have continued to work on the Matched Annotation from NCBI and EMBL-EBI (MANE) project (21) to increase the consistency of annotation between the Ensembl/GENCODE and NCBI’s RefSeq (22) gene sets.”
The UCSC Genome Browser database: 2023 update (2022, background): “0 release of the Matched Annotation from NCBI and EMBLEBI (MANE) project (22), which provides a set of highconfidence transcripts that are identically annotated between RefSeq and Ensembl/GENCODE.”
GENCODE: reference annotation for the human and mouse genomes in 2023 (2022, methodology): “We have essentially completed the project to annotate a single representative ‘MANE Select’ transcript for every human protein-coding gene as part of the Matched Annotation from NCBI and EMBL-EBI (MANE) collaboration (7), thus ensuring that its structure and sequence is identical in the GENCODE and ”
UniProt: the Universal Protein Knowledgebase in 2023 (2022, methodology): “Efforts are also being made to ensure consistency with the Matched Annotation from NCBI and EMBL-EBI (MANE) protein set (24).”
RCSB Protein Data Bank (RCSB.org): delivery of experimentally-determined PDB structures alongside one million computed structure models of proteins from artificial intelligence/machine learning (2022, background): “• From AlphaFold DB: Generated by DeepMind using AlphaFold 2 • Model organism proteomes: 326 175 protein structures from 48 different model organisms • Global health proteomes: 238 274 protein structures from various disease-causing organisms • Swiss-Prot sequences (43): 542 380 protein structures, ”