Sources

Normalized records are constructed by aggregating data from established resources in the genomics community. This section details those data sources and provides a high-level overview of data capture routines and the kinds of information extracted from each source.

Note

Per the GA4GH Variation Representation Specification (VRS), Genomic and cytogenic locations are stored and represented as VRS locations.

HGNC

The HUGO Gene Nomenclature Committee database provides records (referred to as Symbol Reports) for protein-coding genes, pseudogenes, and non-coding RNA genes as designated by the HGNC. [1] Symbol reports contain approved symbols, previously-used symbols, full names, and other relevant information for each approved gene. The Gene Normalizer extracts nomenclature, aliases, cross-references, locus types, and VRS Chromosome Locations for all HGNC gene records. Data is extracted from the latest HGNC JSON release (hgnc_complete_set.json) provided on the HGNC archive page. Computed identifiers are used to identify source accessions.

Example

{
  "concept_id": "hgnc:1097",
  "symbol": "BRAF",
  "symbol_status": "approved",
  "label": "B-Raf proto-oncogene, serine/threonine kinase",
  "strand": null,
  "location_annotations": [],
  "locations": [
    {
      "_id": "ga4gh:VCL.O6yCQ1cnThOrTfK9YUgMlTfM6HTqbrKw",
      "type": "ChromosomeLocation",
      "species_id": "taxonomy:9606",
      "chr": "7",
      "interval": {
        "type": "CytobandInterval",
        "start": "q34",
        "end": "q34"
      }
    }
  ],
  "aliases": [
    "BRAF-1",
    "BRAF1"
  ],
  "previous_symbols": [],
  "xrefs": [
    "ensembl:ENSG00000157764",
    "ncbigene:673"
  ],
  "associated_with": [
    "uniprot:P15056",
    "ena.embl:M95712",
    "pubmed:2284096",
    "ucsc:uc003vwc.5",
    "ccds:CCDS5863",
    "omim:164757",
    "cosmic:BRAF",
    "vega:OTTHUMG00000157457",
    "pubmed:1565476",
    "orphanet:119066",
    "iuphar:1943",
    "ccds:CCDS87555",
    "refseq:NM_004333"
  ],
  "gene_type": "gene with protein product",
  "match_type": 100
}

Ensembl

Ensembl is an online genome browser provided by EMBL-EBI to support research in vertebrates and model organisms. [2] The Gene Normalizer extracts human gene identifiers, names, symbols, cross-references, Ensembl biotypes, and genomic locations for each Ensembl gene record. Data is pulled from the latest Ensembl release listed on the EBI FTP server.

Example

{
  "concept_id": "ensembl:ENSG00000157764",
  "symbol": "BRAF",
  "symbol_status": null,
  "label": "B-Raf proto-oncogene, serine/threonine kinase",
  "strand": "-",
  "location_annotations": [],
  "locations": [
    {
      "_id": "ga4gh:VSL.amNWL6i7F2nbSZAf2QLTRTujxuDrd0pR",
      "type": "SequenceLocation",
      "sequence_id": "ga4gh:SQ.F-LrLMe1SRpfUZHkQmvkVKFEGaoDeHul",
      "interval": {
        "type": "SequenceInterval",
        "start": {
          "type": "Number",
          "value": 140719326
        },
        "end": {
          "type": "Number",
          "value": 140924929
        }
      }
    }
  ],
  "aliases": [],
  "previous_symbols": [],
  "xrefs": [
    "hgnc:1097"
  ],
  "associated_with": [],
  "gene_type": "protein_coding",
  "match_type": 100
}

NCBI Gene

The NCBI Gene Database is a service provided under the NCBI Database mantle, relaying gene nomenclature, reference sequences, pathways, and cross-references to other genomic resources. [3] The Gene Normalizer selects all records for homo sapiens and gathers names, aliases, cross-references, gene types, and cytogenic and genomic loci. Data is sourced from the latest Homo Sapiens release provided on the NCBI FTP server.

Example

{
  "concept_id": "ncbigene:673",
  "symbol": "BRAF",
  "symbol_status": null,
  "label": "B-Raf proto-oncogene, serine/threonine kinase",
  "strand": "-",
  "location_annotations": [],
  "locations": [
    {
      "_id": "ga4gh:VCL.O6yCQ1cnThOrTfK9YUgMlTfM6HTqbrKw",
      "type": "ChromosomeLocation",
      "species_id": "taxonomy:9606",
      "chr": "7",
      "interval": {
        "type": "CytobandInterval",
        "start": "q34",
        "end": "q34"
      }
    },
    {
      "_id": "ga4gh:VSL.xZU3kL8F6t2ca6WH_26CWKfNW9-owhR4",
      "type": "SequenceLocation",
      "sequence_id": "ga4gh:SQ.F-LrLMe1SRpfUZHkQmvkVKFEGaoDeHul",
      "interval": {
        "type": "SequenceInterval",
        "start": {
          "type": "Number",
          "value": 140713327
        },
        "end": {
          "type": "Number",
          "value": 140924929
        }
      }
    }
  ],
  "aliases": [
    "RAFB1",
    "BRAF-1",
    "BRAF1",
    "NS7",
    "B-RAF1",
    "B-raf"
  ],
  "previous_symbols": [],
  "xrefs": [
    "ensembl:ENSG00000157764",
    "hgnc:1097"
  ],
  "associated_with": [
    "omim:164757"
  ],
  "gene_type": "protein-coding",
  "match_type": 100
}

References

[1]

Ruth L Seal, Bryony Braschi, Kristian Gray, Tamsin E M Jones, Susan Tweedie, Liora Haim-Vilmovsky, and Elspeth A Bruford. Genenames.org: the HGNC resources in 2023. Nucleic Acids Research, 51(D1):D1003–D1009, 10 2022. URL: https://doi.org/10.1093/nar/gkac888, arXiv:https://academic.oup.com/nar/article-pdf/51/D1/D1003/48441239/gkac888.pdf, doi:10.1093/nar/gkac888.

[2]

Fergal J Martin, M Ridwan Amode, Alisha Aneja, Olanrewaju Austine-Orimoloye, Andrey G Azov, If Barnes, Arne Becker, Ruth Bennett, Andrew Berry, Jyothish Bhai, Simarpreet Kaur Bhurji, Alexandra Bignell, Sanjay Boddu, Paulo R Branco Lins, Lucy Brooks, Shashank Budhanuru Ramaraju, Mehrnaz Charkhchi, Alexander Cockburn, Luca Da Rin Fiorretto, Claire Davidson, Kamalkumar Dodiya, Sarah Donaldson, Bilal El Houdaigui, Tamara El Naboulsi, Reham Fatima, Carlos Garcia Giron, Thiago Genez, Gurpreet S Ghattaoraya, Jose Gonzalez Martinez, Cristi Guijarro, Matthew Hardy, Zoe Hollis, Thibaut Hourlier, Toby Hunt, Mike Kay, Vinay Kaykala, Tuan Le, Diana Lemos, Diego Marques-Coelho, José Carlos Marugán, Gabriela Alejandra Merino, Louisse Paola Mirabueno, Aleena Mushtaq, Syed Nakib Hossain, Denye N Ogeh, Manoj Pandian Sakthivel, Anne Parker, Malcolm Perry, Ivana Piližota, Irina Prosovetskaia, José G Pérez-Silva, Ahamed Imran Abdul Salam, Nuno Saraiva-Agostinho, Helen Schuilenburg, Dan Sheppard, Swati Sinha, Botond Sipos, William Stark, Emily Steed, Ranjit Sukumaran, Dulika Sumathipala, Marie-Marthe Suner, Likhitha Surapaneni, Kyösti Sutinen, Michal Szpak, Francesca Floriana Tricomi, David Urbina-Gómez, Andres Veidenberg, Thomas A Walsh, Brandon Walts, Elizabeth Wass, Natalie Willhoft, Jamie Allen, Jorge Alvarez-Jarreta, Marc Chakiachvili, Bethany Flint, Stefano Giorgetti, Leanne Haggerty, Garth R Ilsley, Jane E Loveland, Benjamin Moore, Jonathan M Mudge, John Tate, David Thybert, Stephen J Trevanion, Andrea Winterbottom, Adam Frankish, Sarah E Hunt, Magali Ruffier, Fiona Cunningham, Sarah Dyer, Robert D Finn, Kevin L Howe, Peter W Harrison, Andrew D Yates, and Paul Flicek. Ensembl 2023. Nucleic Acids Research, 51(D1):D933–D941, 11 2022. URL: https://doi.org/10.1093/nar/gkac958, arXiv:https://academic.oup.com/nar/article-pdf/51/D1/D933/48440737/gkac958.pdf, doi:10.1093/nar/gkac958.

[3]

Eric W Sayers, Evan E Bolton, J Rodney Brister, Kathi Canese, Jessica Chan, Donald C Comeau, Ryan Connor, Kathryn Funk, Chris Kelly, Sunghwan Kim, Tom Madej, Aron Marchler-Bauer, Christopher Lanczycki, Stacy Lathrop, Zhiyong Lu, Francoise Thibaud-Nissen, Terence Murphy, Lon Phan, Yuri Skripchenko, Tony Tse, Jiyao Wang, Rebecca Williams, Barton W Trawick, Kim D Pruitt, and Stephen T Sherry. Database resources of the national center for biotechnology information. Nucleic Acids Res., 50(D1):D20–D26, January 2022.