Cbioportal: Normalize Reference Information for Genes

[inodb]

Currently we have a gene to transcript mapping in cBioPortal and there is one in Genome Nexus (https://github.com/genome-nexus/genome-nexus-importer/blob/master/data/grch37_ensembl92/export/ensembl_biomart_canonical_transcripts_per_hgnc.txt). We should try to have a single one.

• [ ] Check if the Genome Nexus mappings work for cBioPortal
• [ ] Check if the Genome Nexus mappings work for OncoKB
• [ ] regenerate the cbioportal seed database
• [ ] normalize oncokb genes

Further discussion:

• When importing MAF into cBioPortal we use the Entrez ID. Is it possible that sometimes entrez ids get imported that don't have an associated hugo symbol? This would make it impossible to query the data
• cBioPortal doesn't really have a gene to ensembl transcript mapping, but rather gene to entrez id where entrez id represents a particular transcript (?)
• datahub now uses some JSON dump from cBioPortal to validate the mutation file. This differs from live cBioPortal
• Should we use hugo symbol in cBioPortal over Entrez Id?

Check:

• [ ] Is it correct that most of our data has an entrez id? And how is this computed if it doesn't exist?
• [ ] How many MAF files don't have genomic location information?

CC @sheridancbio @n1zea144 @zhx828 @jjgao

[jjgao]

Thanks, @inodb.

Just copied all the columns below and let's discuss which ones to keep or add.

hgnc_symbol | KMT2B | KMT2D |  
-- | -- | -- | --
ensembl_canonical_gene | ENSG00000272333 | ENSG00000167548
ensembl_canonical_transcript | ENST00000222270 | ENST00000301067
genome_nexus_canonical_transcript | ENST00000222270 | ENST00000301067
uniprot_canonical_transcript | ENST00000420124 | ENST00000301067
mskcc_canonical_transcript | ENST00000222270 | ENST00000301067
hgnc_id | HGNC:15840 | HGNC:7133 |  
approved_name | lysine methyltransferase 2B | lysine methyltransferase 2D
locus_group | protein-coding gene | protein-coding gene
locus_type | gene with protein product | gene with protein product
status | Approved | Approved |  
chromosome | 19q13.12 | 12q13.12 |  
location_sortable | 19q13.12 | 12q13.12 |  
synonyms | KIAA0304, MLL2, TRX2, HRX2, WBP7, MLL1B, MLL4, CXXC10 | ALR, MLL4, CAGL114
alias_name | myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila) 4, Histone-lysine N-methyltransferase 2B | histone-lysine N-methyltransferase 2D
previous_symbols |   | TNRC21, MLL2
prev_name | lysine (K)-specific methyltransferase 2B | trinucleotide repeat containing 21, myeloid/lymphoid or mixed-lineage leukemia 2, lysine (K)-specific methyltransferase 2D
gene_family | PHD finger proteins, Zinc fingers CXXC-type, Lysine methyltransferases, SET domain containing | PHD finger proteins, Lysine methyltransferases, Trinucleotide repeat containing, SET domain containing
gene_family_id | 88, 136, 487, 1399 | 88, 487, 775, 1399
date_approved_reserved | 5/9/13 | 10/14/98 |  
date_symbol_changed |   | 5/9/13 |  
date_name_changed | 2/12/16 | 2/12/16 |  
date_modified | 3/6/18 | 3/6/18 |  
entrez_gene_id | 9757 | 8085 |  
vega_id | OTTHUMG00000048119 | OTTHUMG00000166524
ucsc_id |   |   |  
accession_numbers | AJ007041 | AF010403 |  
refseq_ids | NM_014727 | NM_003482 |  
ccds_id | CCDS46055 | CCDS44873 |  
uniprot_id | Q9UMN6 | O14686 |  
pubmed_id | 10409430, 10637508 | 9247308 |  
mgd_id | MGI:109565 | MGI:2682319
rgd_id | RGD:7678027 | RGD:2324324
lsdb |   |   |  
cosmic |   | KMT2D |  
omim_id | 606834 | 602113 |  
mirbase |   |   |  
homeodb |   |   |  
snornabase |   |   |  
bioparadigms_slc |   |   |  
orphanet |   | 239011 |  
pseudogene.org |   |   |  
horde_id |   |   |  
merops |   |   |  
imgt |   |   |  
iuphar | objectId:2689 | objectId:2691
kznf_gene_catalog |   |   |  
mamit-trnadb |   |   |  
cd |   |   |  
lncrnadb |   |   |  
enzyme_id |   |   |  
intermediate_filament_db |   |   |  
rna_central_ids |   |   |  

[jjgao]

I looked at our cbioportal database, I think the data above covers everything we need. (We don't have length, but I think we can remove the LENGTH COLUMN in the GENE table now - it was previously used in the Mutated Genes tab).

@n1zea144 could someone in your group also take a look, e.g. check all genes in the current portal database are covered.

@zhx828 could you check if all genes in oncokb are covered?

[zhx828]

@inodb @jjgao I think due to recent gene updates in portal, some genes in OncoKB are no longer match with GN and portal. I will need to update the genes in the next release.
https://docs.google.com/spreadsheets/d/1mqmH1ccKWli7te7L8v0lIQh6uWbnSf2gu07l76RL-gI/edit?usp=sharing

[n1zea144]

I will ask one of the curators (probably @rmadupuri) to take a look at gene coverage.

[zhx828]

@inodb These two genes in GN use different uniport isoforms comparing to the vcf2mac uniport file

gene | isoform
-- | --
HIST1H2BO | ENST00000616182
ARID3B | ENST00000622429

[jjgao]

@inodb @zhx828 @n1zea144 @rmadupuri please prioritize this one. This will fix a couple of existing issues, e.g. #5910 and cBioPortal/datahub#540 and will give us a clean start to re-import all studies.

[rmadupuri]

Hi @jjgao, the following genes in database did not have matches in GN. Divided them to 4 sheets.
https://docs.google.com/spreadsheets/d/1JCx12E86TGbMydRuzwFSUVgJ2HwlGAvKFViDfgaEK2U/edit?usp=sharing

1. 76 Protein coding genes (Sheet 1)
2. 1820 genes of other types (ncRNA, pseudo, rRNA, scRNA, tRNA, biological-region) (Sheet 2)
3. 24,925 genes whose name starts with LOC.. (Sheet 3) (not sure if needed)
4. 373 miRNA genes (Sheet 4)

The above miRNA's might have been covered in GN but its not easy to compare since the portal has negative entrez ids and GN has positive ids.

[jjgao]

I looked at a few protein-coding genes:

• GAGE3 was withdrawn: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:4100
• FAM240C is a placeholder symbol (not sure what that means): https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:54200
• ZNF765-ZNF761 does not seem to have a hugo symbol: https://www.ncbi.nlm.nih.gov/gene/110116772
• LITAFD seems regular: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:53927

We should do a more systematic analysis. Before doing that, I am wondering if you can help to add a couple of more columns in the spreadsheet so that we know how much data are there for each gene in the public portal? @rmadupuri

• number of mutations of each gene in mutation_event table
• number of rows of each gene in genetic_alteration table

[jjgao]

related issue https://github.com/cBioPortal/cbioportal/issues/6432

[jjgao]

Once we switch, it is also an opportunity to switch to previous symbols instead of synonyms and hopefully remove manny ambiguity, e.g. mll2. We maybe able too remove this file too: https://github.com/cBioPortal/cbioportal/blob/master/core/src/main/resources/gene_symbol_disambiguation.txt.

[n1zea144]

Hi @jjgao - @inodb and I met yesterday to discuss this effort and we have some thoughts about this that I will outline in a google doc / rfc. I'll link back once I have a draft.

[n1zea144]

@jjgao Per our discussion, we will revisit the utility of Entrez, or Ensembl id's in a later effort. With that, we can build out the roadmap of work to be done on this issue. cc: @inodb

Here is link to RFC:
Gene Data RFC

[stale[bot]]

This issue has been automatically marked as stale because it has not had recent activity. It will be closed if no further activity occurs. Thank you for your contributions.

[inodb]

still an issue

[jjgao]

@inodb what's the status on this? Should we turn it into an epic?

[ritikakundra]

@inodb @jjgao This is now part of our scrum planning (been for 2 weeks). We have been working on finding the best source for our gene table and whatever utilization leads to what kind of data loss.

[stale[bot]]

This issue has been automatically marked as stale because it has not had recent activity. It will be closed if no further activity occurs. Thank you for your contributions.

[stale[bot]]

This issue has been automatically marked as stale because it has not had recent activity. It will be closed if no further activity occurs. Thank you for your contributions.

[stale[bot]]

This issue has been automatically marked as stale because it has not had recent activity. It will be closed if no further activity occurs. Thank you for your contributions.

[stale[bot]]

This issue has been automatically marked as stale because it has not had recent activity. It will be closed if no further activity occurs. Thank you for your contributions.