Add a select transcripts = select feature

Peter-J-Freeman commented 3 years ago

Is your feature request related to a problem? Please describe. Not related to a problem but will be an upgrade of the select_transcripts feature

Describe the solution you'd like

We now log select status, MANE, RefSeq, Ensembl. If we add select_transcripts = select, the tool will only return transcripts that these projects consider select (We will eventually expand to clinical for mane + clinical)
Need to also update the interactive gene2transcript table to show select status

Peter-J-Freeman commented 3 years ago

@ifokkema you may like what's coming

Peter-J-Freeman commented 3 years ago

The default behaviour of select_transcript = "all" or a list of transcripts remains

Added the following

>>> import json
>>> import VariantValidator
>>> vval = VariantValidator.Validator()
>>> variant = 'NC_000017.10:g.48275363C>A'
>>> genome_build = 'GRCh37'
>>> select_transcripts = 'select'
>>> validate = vval.validate(variant, genome_build, select_transcripts)
>>> validation = validate.format_as_dict(with_meta=True)
>>> print(validation)
{'flag': 'gene_variant', 

'NM_000088.4:c.589G>T': {'selected_assembly': 'GRCh37', 'submitted_variant': 'NC_000017.10:g.48275363C>A', 'gene_symbol': 'COL1A1', 'gene_ids': {'hgnc_id': 'HGNC:2197', 'entrez_gene_id': '1277', 'ensembl_gene_id': 'ENSG00000108821', 'ucsc_id': 'uc002iqm.4', 'omim_id': ['120150'], 'ccds_ids': ['CCDS11561']}, 'annotations': {'db_xref': {'CCDS': 'CCDS11561.1', 'select': 'MANE', 'ncbigene': '1277', 'ensemblgene': None, 'hgnc': 'HGNC:2197'}, 'chromosome': '17', 'map': '17q21.33', 'note': 'collagen type I alpha 1 chain', 'variant': '0', 'refseq_select': True, 'mane_select': True, 'ensembl_select': False, 'mane_plus_clinical': False}, 'transcript_description': 'Homo sapiens collagen type I alpha 1 chain (COL1A1), mRNA', 'hgvs_transcript_variant': 'NM_000088.4:c.589G>T', 'genome_context_intronic_sequence': '', 'refseqgene_context_intronic_sequence': '', 'hgvs_refseqgene_variant': '', 'hgvs_predicted_protein_consequence': {'tlr': 'NP_000079.2:p.(Gly197Cys)', 'slr': 'NP_000079.2:p.(G197C)', 'lrg_tlr': 'LRG_1p1:p.(Gly197Cys)', 'lrg_slr': 'LRG_1p1:p.(G197C)'}, 'validation_warnings': ['RefSeqGene record not available'], 'hgvs_lrg_transcript_variant': '', 'hgvs_lrg_variant': '', 'alt_genomic_loci': [], 'primary_assembly_loci': {'grch37': {'hgvs_genomic_description': 'NC_000017.10:g.48275363C>A', 'vcf': {'chr': '17', 'pos': '48275363', 'ref': 'C', 'alt': 'A'}}, 'hg19': {'hgvs_genomic_description': 'NC_000017.10:g.48275363C>A', 'vcf': {'chr': 'chr17', 'pos': '48275363', 'ref': 'C', 'alt': 'A'}}, 'grch38': {'hgvs_genomic_description': 'NC_000017.11:g.50198002C>A', 'vcf': {'chr': '17', 'pos': '50198002', 'ref': 'C', 'alt': 'A'}}, 'hg38': {'hgvs_genomic_description': 'NC_000017.11:g.50198002C>A', 'vcf': {'chr': 'chr17', 'pos': '50198002', 'ref': 'C', 'alt': 'A'}}}, 'reference_sequence_records': {'transcript': 'https://www.ncbi.nlm.nih.gov/nuccore/NM_000088.4', 'protein': 'https://www.ncbi.nlm.nih.gov/nuccore/NP_000079.2'}}, 

'NM_000088.3:c.589G>T': {'selected_assembly': 'GRCh37', 'submitted_variant': 'NC_000017.10:g.48275363C>A', 'gene_symbol': 'COL1A1', 'gene_ids': {'hgnc_id': 'HGNC:2197', 'entrez_gene_id': '1277', 'ensembl_gene_id': 'ENSG00000108821', 'ucsc_id': 'uc002iqm.4', 'omim_id': ['120150'], 'ccds_ids': ['CCDS11561']}, 'annotations': {'db_xref': {'CCDS': 'CCDS11561.1', 'select': 'RefSeq', 'ncbigene': '1277', 'ensemblgene': None, 'hgnc': 'HGNC:2197'}, 'chromosome': '17', 'map': '17q21.33', 'note': 'collagen type I alpha 1 chain', 'variant': '0', 'refseq_select': True, 'mane_select': False, 'ensembl_select': False, 'mane_plus_clinical': False}, 'transcript_description': 'Homo sapiens collagen type I alpha 1 chain (COL1A1), mRNA', 'hgvs_transcript_variant': 'NM_000088.3:c.589G>T', 'genome_context_intronic_sequence': '', 'refseqgene_context_intronic_sequence': '', 'hgvs_refseqgene_variant': 'NG_007400.1:g.8638G>T', 'hgvs_predicted_protein_consequence': {'tlr': 'NP_000079.2:p.(Gly197Cys)', 'slr': 'NP_000079.2:p.(G197C)', 'lrg_tlr': 'LRG_1p1:p.(Gly197Cys)', 'lrg_slr': 'LRG_1p1:p.(G197C)'}, 'validation_warnings': ['A more recent version of the selected reference sequence NM_000088.3 is available (NM_000088.4): NM_000088.4:c.589G>T MUST be fully validated prior to use in reports: select_variants=NM_000088.4:c.589G>T', 'RefSeqGene record not available'], 'hgvs_lrg_transcript_variant': 'LRG_1t1:c.589G>T', 'hgvs_lrg_variant': 'LRG_1:g.8638G>T', 'alt_genomic_loci': [], 'primary_assembly_loci': {'grch37': {'hgvs_genomic_description': 'NC_000017.10:g.48275363C>A', 'vcf': {'chr': '17', 'pos': '48275363', 'ref': 'C', 'alt': 'A'}}, 'hg19': {'hgvs_genomic_description': 'NC_000017.10:g.48275363C>A', 'vcf': {'chr': 'chr17', 'pos': '48275363', 'ref': 'C', 'alt': 'A'}}, 'grch38': {'hgvs_genomic_description': 'NC_000017.11:g.50198002C>A', 'vcf': {'chr': '17', 'pos': '50198002', 'ref': 'C', 'alt': 'A'}}, 'hg38': {'hgvs_genomic_description': 'NC_000017.11:g.50198002C>A', 'vcf': {'chr': 'chr17', 'pos': '50198002', 'ref': 'C', 'alt': 'A'}}}, 'reference_sequence_records': {'transcript': 'https://www.ncbi.nlm.nih.gov/nuccore/NM_000088.3', 'protein': 'https://www.ncbi.nlm.nih.gov/nuccore/NP_000079.2', 'refseqgene': 'https://www.ncbi.nlm.nih.gov/nuccore/NG_007400.1', 'lrg': 'http://ftp.ebi.ac.uk/pub/databases/lrgex/LRG_1.xml'}}, 

'metadata': {'variantvalidator_version': '1.0.4.dev214+g9cf795f.d20210407', 'variantvalidator_hgvs_version': '2.0.1.dev1+gb3a18e0', 'vvta_version': 'vvta_2021_2', 'vvseqrepo_db': 'VV_SR_2021_2/master', 'vvdb_version': 'vvdb_2021_4'}}

Peter-J-Freeman commented 3 years ago

>>> import json
>>> import VariantValidator
>>> vval = VariantValidator.Validator()
>>> variant = 'NC_000017.10:g.48275363C>A'
>>> genome_build = 'GRCh37'
>>> select_transcripts = 'mane_select'
>>> validate = vval.validate(variant, genome_build, select_transcripts)
>>> validation = validate.format_as_dict(with_meta=True)
>>> print(validation)
{'flag': 'gene_variant', 

'NM_000088.4:c.589G>T': {'selected_assembly': 'GRCh37', 'submitted_variant': 'NC_000017.10:g.48275363C>A', 'gene_symbol': 'COL1A1', 'gene_ids': {'hgnc_id': 'HGNC:2197', 'entrez_gene_id': '1277', 'ensembl_gene_id': 'ENSG00000108821', 'ucsc_id': 'uc002iqm.4', 'omim_id': ['120150'], 'ccds_ids': ['CCDS11561']}, 'annotations': {'db_xref': {'CCDS': 'CCDS11561.1', 'select': 'MANE', 'ncbigene': '1277', 'ensemblgene': None, 'hgnc': 'HGNC:2197'}, 'chromosome': '17', 'map': '17q21.33', 'note': 'collagen type I alpha 1 chain', 'variant': '0', 'refseq_select': True, 'mane_select': True, 'ensembl_select': False, 'mane_plus_clinical': False}, 'transcript_description': 'Homo sapiens collagen type I alpha 1 chain (COL1A1), mRNA', 'hgvs_transcript_variant': 'NM_000088.4:c.589G>T', 'genome_context_intronic_sequence': '', 'refseqgene_context_intronic_sequence': '', 'hgvs_refseqgene_variant': '', 'hgvs_predicted_protein_consequence': {'tlr': 'NP_000079.2:p.(Gly197Cys)', 'slr': 'NP_000079.2:p.(G197C)', 'lrg_tlr': 'LRG_1p1:p.(Gly197Cys)', 'lrg_slr': 'LRG_1p1:p.(G197C)'}, 'validation_warnings': ['RefSeqGene record not available'], 'hgvs_lrg_transcript_variant': '', 'hgvs_lrg_variant': '', 'alt_genomic_loci': [], 'primary_assembly_loci': {'grch37': {'hgvs_genomic_description': 'NC_000017.10:g.48275363C>A', 'vcf': {'chr': '17', 'pos': '48275363', 'ref': 'C', 'alt': 'A'}}, 'hg19': {'hgvs_genomic_description': 'NC_000017.10:g.48275363C>A', 'vcf': {'chr': 'chr17', 'pos': '48275363', 'ref': 'C', 'alt': 'A'}}, 'grch38': {'hgvs_genomic_description': 'NC_000017.11:g.50198002C>A', 'vcf': {'chr': '17', 'pos': '50198002', 'ref': 'C', 'alt': 'A'}}, 'hg38': {'hgvs_genomic_description': 'NC_000017.11:g.50198002C>A', 'vcf': {'chr': 'chr17', 'pos': '50198002', 'ref': 'C', 'alt': 'A'}}}, 'reference_sequence_records': {'transcript': 'https://www.ncbi.nlm.nih.gov/nuccore/NM_000088.4', 'protein': 'https://www.ncbi.nlm.nih.gov/nuccore/NP_000079.2'}}, 

'metadata': {'variantvalidator_version': '1.0.4.dev214+g9cf795f.d20210407', 'variantvalidator_hgvs_version': '2.0.1.dev1+gb3a18e0', 'vvta_version': 'vvta_2021_2', 'vvseqrepo_db': 'VV_SR_2021_2/master', 'vvdb_version': 'vvdb_2021_4'}}
>>>

Peter-J-Freeman commented 3 years ago

>>> import json
>>> import VariantValidator
>>> vval = VariantValidator.Validator()
>>> variant = 'NC_000017.10:g.48275363C>A'
>>> genome_build = 'GRCh37'
>>> select_transcripts = 'refseq_select'
>>> validate = vval.validate(variant, genome_build, select_transcripts)
>>> validation = validate.format_as_dict(with_meta=True)
>>> print(validation)
{'flag': 'gene_variant', 

'NM_000088.4:c.589G>T': {'selected_assembly': 'GRCh37', 'submitted_variant': 'NC_000017.10:g.48275363C>A', 'gene_symbol': 'COL1A1', 'gene_ids': {'hgnc_id': 'HGNC:2197', 'entrez_gene_id': '1277', 'ensembl_gene_id': 'ENSG00000108821', 'ucsc_id': 'uc002iqm.4', 'omim_id': ['120150'], 'ccds_ids': ['CCDS11561']}, 'annotations': {'db_xref': {'CCDS': 'CCDS11561.1', 'select': 'MANE', 'ncbigene': '1277', 'ensemblgene': None, 'hgnc': 'HGNC:2197'}, 'chromosome': '17', 'map': '17q21.33', 'note': 'collagen type I alpha 1 chain', 'variant': '0', 'refseq_select': True, 'mane_select': True, 'ensembl_select': False, 'mane_plus_clinical': False}, 'transcript_description': 'Homo sapiens collagen type I alpha 1 chain (COL1A1), mRNA', 'hgvs_transcript_variant': 'NM_000088.4:c.589G>T', 'genome_context_intronic_sequence': '', 'refseqgene_context_intronic_sequence': '', 'hgvs_refseqgene_variant': '', 'hgvs_predicted_protein_consequence': {'tlr': 'NP_000079.2:p.(Gly197Cys)', 'slr': 'NP_000079.2:p.(G197C)', 'lrg_tlr': 'LRG_1p1:p.(Gly197Cys)', 'lrg_slr': 'LRG_1p1:p.(G197C)'}, 'validation_warnings': ['RefSeqGene record not available'], 'hgvs_lrg_transcript_variant': '', 'hgvs_lrg_variant': '', 'alt_genomic_loci': [], 'primary_assembly_loci': {'grch37': {'hgvs_genomic_description': 'NC_000017.10:g.48275363C>A', 'vcf': {'chr': '17', 'pos': '48275363', 'ref': 'C', 'alt': 'A'}}, 'hg19': {'hgvs_genomic_description': 'NC_000017.10:g.48275363C>A', 'vcf': {'chr': 'chr17', 'pos': '48275363', 'ref': 'C', 'alt': 'A'}}, 'grch38': {'hgvs_genomic_description': 'NC_000017.11:g.50198002C>A', 'vcf': {'chr': '17', 'pos': '50198002', 'ref': 'C', 'alt': 'A'}}, 'hg38': {'hgvs_genomic_description': 'NC_000017.11:g.50198002C>A', 'vcf': {'chr': 'chr17', 'pos': '50198002', 'ref': 'C', 'alt': 'A'}}}, 'reference_sequence_records': {'transcript': 'https://www.ncbi.nlm.nih.gov/nuccore/NM_000088.4', 'protein': 'https://www.ncbi.nlm.nih.gov/nuccore/NP_000079.2'}}, 

'NM_000088.3:c.589G>T': {'selected_assembly': 'GRCh37', 'submitted_variant': 'NC_000017.10:g.48275363C>A', 'gene_symbol': 'COL1A1', 'gene_ids': {'hgnc_id': 'HGNC:2197', 'entrez_gene_id': '1277', 'ensembl_gene_id': 'ENSG00000108821', 'ucsc_id': 'uc002iqm.4', 'omim_id': ['120150'], 'ccds_ids': ['CCDS11561']}, 'annotations': {'db_xref': {'CCDS': 'CCDS11561.1', 'select': 'RefSeq', 'ncbigene': '1277', 'ensemblgene': None, 'hgnc': 'HGNC:2197'}, 'chromosome': '17', 'map': '17q21.33', 'note': 'collagen type I alpha 1 chain', 'variant': '0', 'refseq_select': True, 'mane_select': False, 'ensembl_select': False, 'mane_plus_clinical': False}, 'transcript_description': 'Homo sapiens collagen type I alpha 1 chain (COL1A1), mRNA', 'hgvs_transcript_variant': 'NM_000088.3:c.589G>T', 'genome_context_intronic_sequence': '', 'refseqgene_context_intronic_sequence': '', 'hgvs_refseqgene_variant': 'NG_007400.1:g.8638G>T', 'hgvs_predicted_protein_consequence': {'tlr': 'NP_000079.2:p.(Gly197Cys)', 'slr': 'NP_000079.2:p.(G197C)', 'lrg_tlr': 'LRG_1p1:p.(Gly197Cys)', 'lrg_slr': 'LRG_1p1:p.(G197C)'}, 'validation_warnings': ['A more recent version of the selected reference sequence NM_000088.3 is available (NM_000088.4): NM_000088.4:c.589G>T MUST be fully validated prior to use in reports: select_variants=NM_000088.4:c.589G>T', 'RefSeqGene record not available'], 'hgvs_lrg_transcript_variant': 'LRG_1t1:c.589G>T', 'hgvs_lrg_variant': 'LRG_1:g.8638G>T', 'alt_genomic_loci': [], 'primary_assembly_loci': {'grch37': {'hgvs_genomic_description': 'NC_000017.10:g.48275363C>A', 'vcf': {'chr': '17', 'pos': '48275363', 'ref': 'C', 'alt': 'A'}}, 'hg19': {'hgvs_genomic_description': 'NC_000017.10:g.48275363C>A', 'vcf': {'chr': 'chr17', 'pos': '48275363', 'ref': 'C', 'alt': 'A'}}, 'grch38': {'hgvs_genomic_description': 'NC_000017.11:g.50198002C>A', 'vcf': {'chr': '17', 'pos': '50198002', 'ref': 'C', 'alt': 'A'}}, 'hg38': {'hgvs_genomic_description': 'NC_000017.11:g.50198002C>A', 'vcf': {'chr': 'chr17', 'pos': '50198002', 'ref': 'C', 'alt': 'A'}}}, 'reference_sequence_records': {'transcript': 'https://www.ncbi.nlm.nih.gov/nuccore/NM_000088.3', 'protein': 'https://www.ncbi.nlm.nih.gov/nuccore/NP_000079.2', 'refseqgene': 'https://www.ncbi.nlm.nih.gov/nuccore/NG_007400.1', 'lrg': 'http://ftp.ebi.ac.uk/pub/databases/lrgex/LRG_1.xml'}}, 

'metadata': {'variantvalidator_version': '1.0.4.dev214+g9cf795f.d20210407', 'variantvalidator_hgvs_version': '2.0.1.dev1+gb3a18e0', 'vvta_version': 'vvta_2021_2', 'vvseqrepo_db': 'VV_SR_2021_2/master', 'vvdb_version': 'vvdb_2021_4'}}
>>>

Peter-J-Freeman commented 3 years ago

Needs testing, but this should be available to the API immediately (will need documenting - and will be ready when the servers are built) and should work in the batch tool. Again, needs documenting

ifokkema commented 3 years ago

Thanks for the tag! Since we might not know if there are any MANE select transcripts available, it would likely be more efficient to make just one call instead of two (i.e., select all and check for MANE transcripts rather than requesting for MANE transcripts, no results, select again for all). Actually, I think that's also best in the LOVD interface - show all, but highlight the MANE select transcript.

Peter-J-Freeman commented 3 years ago

Since we might not know if there are any MANE select transcripts available, it would likely be more efficient to make just one call instead of two (i.e., select all and check for MANE transcripts rather than requesting for MANE transcripts, no results, select again for all). Actually, I think that's also best in the LOVD interface - show all, but highlight the MANE select transcript.

Yep, this is why I used the tag "select". We can safely assume, I would hope at least, that every gene will have a RefSeq select (and ensembl select when relevant).

So for your purposes, use "select" rather than "all"

Options are

select Returns all transcripts deemed as “canonical” by reference sequence databases
mane_select Returns all transcripts deemed as “canonical” by the MANE project
refseq_select Returns all transcripts deemed as “canonical” by the RefSeq sequence database

Peter-J-Freeman commented 3 years ago

Updated the code in VV and VVweb

https://github.com/openvar/VVweb/commit/9755d14a01ad1b0d24952354c0ac9a3d9f263ecf

https://github.com/openvar/variantValidator/commit/9fefb3bf44a05758f43ebf6b55f4a84ccb55cf14

Peter-J-Freeman commented 3 years ago

Closes this issue

openvar / variantValidator

Add a select transcripts = select feature #298