Biomarkers: pharma biomarkers | Pharma Observatory

A gene, protein variant or other biomarker with the evidence recorded for it.

Id: A biomarker route key, the id the web pages use: the gene symbol for a gene (BRAF, ERBB2), f.<feature> for a feature (f.pd-l1), v.<gene>.<change>.<hash> for a protein variant. Every biomarker dataset takes this same key. Evidence, literature, publishing-company and variant-mention datasets are gene-level: enter on the gene's route key. Matching is exact, case included.

Commands

Biomarkers commands
Command	Reads
`pharma biomarkers list`	Biomarkers
pharma biomarkers get <id>	One biomarker and the datasets reachable from it
`pharma biomarkers get <id> biomarker-bqp-assertions`	FDA biomarker qualification projects
`pharma biomarkers get <id> biomarker-cdx-assertions`	FDA companion diagnostic assertions
`pharma biomarkers get <id> biomarker-evidence`	Biomarker evidence
`pharma biomarkers get <id> biomarker-literature`	Trial-cited literature mentions
`pharma biomarkers get <id> biomarker-publishing-companies`	Companies publishing on a biomarker
`pharma biomarkers get <id> biomarker-relations`	Literature-extracted relations
`pharma biomarkers get <id> biomarker-sample-coverage`	Human sample screening coverage (GDC)
`pharma biomarkers get <id> biomarker-sample-prevalence`	Human sample screening reference (GDC cohorts)
`pharma biomarkers get <id> biomarker-validation`	Biomarker validation ladder
`pharma biomarkers get <id> biomarker-variant-mentions`	Protein variant mentions

Every command takes the paging, sorting and output flags described on the CLI page; the CLI prints the source credit with every result.

Pharma Observatory CLI

Biomarkers

pharma biomarkers list

The biomarkers object type's primary dataset, with the evidence counts by type.

One row per: biomarker (a gene, protein variant or other feature)
Key columns: biomarker_id

Source: Cancer Genome Interpreter, IRB Barcelona/ICREA/UPF (CC BY 4.0); UniProt (CC BY 4.0); ClinicalTrials.gov via AACT, CTTI (CC BY); NCI Genomic Data Commons; Open Targets Platform (CC0); PubMed, NCBI/NLM; US FDA

Columns 26

Biomarkers columns
Column	Type	Unit	Description
biomarker_id	text		The biomarker key.
route_key	text		The biomarker's route key, the id the web page uses and the one entry key every biomarker dataset takes (the gene symbol for a gene biomarker).
biomarker_kind	text		gene, protein_variant or another feature kind.
identity_status	text		Whether the biomarker's identity is confirmed.
display_name	text		The biomarker's display name.
parent_biomarker_id	text		The parent biomarker (a variant's gene).
gene_symbol	text		The gene symbol.
amino_acid_change	text		The amino-acid change, for a variant.
target_id	text		The target's Ensembl gene id.
hgnc_id	text		The HUGO Gene Nomenclature Committee (HGNC) gene id.
uniprot_accession	text		The UniProt accession.
feature_code	text		Feature code for a non-gene feature.
feature_type	text		Feature type for a non-gene feature.
evidence_tier	integer		Strongest evidence tier: 1 companion diagnostic of the US Food and Drug Administration (FDA) through 6 no evidence.
evidence_tier_label	text		The tier's name.
n_fda_cdx_assertions	integer	assertions	FDA companion diagnostic assertions.
n_fda_bqp_assertions	integer	assertions	FDA biomarker qualification project assertions.
n_cancer_actionable_cgi	integer	assertions	Cancer Genome Interpreter actionable rows.
n_ot_association	integer	associations	Open Targets target-disease associations.
n_trial_mention	integer	trial mentions	Trials that name the biomarker.
n_publication_variant_mentions	integer	papers	Publication variant mentions.
has_clinical_validation_evidence	boolean		Whether clinical validation evidence exists.
has_analytical_validation_evidence	boolean		Whether analytical validation evidence exists.
n_assay_provider_papers	integer	papers	Papers naming an assay provider for the biomarker.
n_assay_provider_suppliers	integer		Assay-provider suppliers named.
n_diagnostic_provider_suppliers	integer		Of those, diagnostic providers.

FDA biomarker qualification projects

pharma biomarkers get <id> biomarker-bqp-assertions

Projects in the US Food and Drug Administration (FDA) Biomarker Qualification Program for a biomarker, with the submitter's company and group keys. Only a source status of exactly qualified is FDA-qualified.

One row per: FDA Biomarker Qualification Program assertion for a biomarker
Key columns: source_assertion_id

Source: US FDA

Columns 23

FDA biomarker qualification projects columns
Column	Type	Description
source_assertion_id	text	The assertion id.
route_key	text	The biomarker's route key, the entry key for the biomarkers object type.
biomarker_id	text	The biomarker key.
ddt_number	text	The drug development tool number the US Food and Drug Administration (FDA) assigns the project.
ddt_project_id	text	The FDA project id.
project_name	text	The project's name.
bqp_signal	text	The source status of the project. Only qualified means FDA-qualified; every other value is a project status.
is_fda_qualified	boolean	True only when the source status is exactly qualified.
submission_status	text	The submission status as the source words it.
submission_stage	text	The submission stage as the source words it.
submitter_name	text	The submitter as the source names it.
submitter_org_id	text	Legal-entity level: the organization record the submitter resolved to (null when unresolved).
submitter_company_id	text	Company level: the company the submitter belongs to (null when unresolved).
submitter_company_name	text	Display name of the submitter's company.
submitter_group_id	text	Group level: the submitter's current ultimate parent company; a root company's group is itself.
submitter_group_name	text	Display name of the submitter's group.
submitter_match_tier	text	How the submitter name matched an organization record.
submitter_role	text	The submitter's role on the project.
biomarker_role	text	The biomarker's role in the project (for example a diagnostic or a surrogate endpoint).
biomarker_role_method	text	How the biomarker role was assigned.
is_surrogate_endpoint_claim	boolean	True when the project claims a surrogate endpoint.
source_url	text	Link to the FDA project page.
snapshot_date	date	The date the source list was captured.

FDA companion diagnostic assertions

pharma biomarkers get <id> biomarker-cdx-assertions

Companion diagnostics of the US Food and Drug Administration (FDA) for a biomarker, one row per assertion, with the manufacturer's company and group keys.

One row per: FDA companion diagnostic assertion for a biomarker
Key columns: source_assertion_id

Source: US FDA

Columns 17

FDA companion diagnostic assertions columns
Column	Type	Description
source_assertion_id	text	The assertion id.
route_key	text	The biomarker's route key, the entry key for the biomarkers object type.
biomarker_id	text	The biomarker key.
biomarker_token	text	The biomarker as the FDA list names it.
diagnostic_name	text	The companion diagnostic's name.
indication	text	The indication.
sample_type	text	The sample type.
submission_cell	text	The submission number cell as listed.
latest_stated_decision_date	date	Latest decision date the list states.
source_url	text	Link to the FDA list.
manufacturer_name	text	The manufacturer as filed.
manufacturer_org_id	text	Legal-entity level: the organization record the manufacturer resolved to (null when unresolved).
manufacturer_company_id	text	Company level: the company the manufacturer belongs to (null when unresolved).
manufacturer_company_name	text	Display name of the manufacturer's company.
manufacturer_group_id	text	Group level: the manufacturer's current ultimate parent company; a root company's group is itself.
manufacturer_group_name	text	Display name of the manufacturer's group.
manufacturer_match_tier	text	How firmly the manufacturer name matched an organization.

Biomarker evidence

pharma biomarkers get <id> biomarker-evidence

One evidence dataset in place of the cgi, ot_association and trial_mention sections: filter by evidence_type.

One row per: evidence assertion
Key columns: biomarker_evidence_id

Source: Cancer Genome Interpreter, IRB Barcelona/ICREA/UPF (CC BY 4.0); Open Targets Platform (CC0); ClinicalTrials.gov via AACT, CTTI (CC BY)

Columns 19

Biomarker evidence columns
Column	Type	Unit	Description
biomarker_evidence_id	text		The evidence assertion id.
route_key	text		The biomarker route key of the gene this evidence is about (the gene symbol); the entry key for the biomarkers object type.
gene_symbol	text		The gene symbol the evidence is about.
target_id	text		The target's Ensembl gene id.
uniprot_accession	text		The UniProt accession.
biomarker	text		The biomarker as the source names it (the gene or the variant).
evidence_type	text		cancer_actionable_cgi, ot_association or trial_mention.
source	text		The source the assertion comes from.
condition_id	text		The condition key.
condition_name	text		The condition as the source names it.
therapeutic_area	text		The therapeutic area.
drug_name	text		The drug as filed.
drug_id	text		The drug key.
molecule_id	text		The molecule key. Null on every row: no evidence row carries a molecule.
response	text		The reported response (for example Responsive, Resistant).
score	double		The association score, for an Open Targets row.
variant_count	integer	variants	Variants the assertion covers.
trial_id	text		The trial registry id, for a trial-mention row.
sample_type	text		The sample type, for a trial-mention row.

Trial-cited literature mentions

pharma biomarkers get <id> biomarker-literature

Papers in the trial-cited corpus whose annotation names a biomarker gene, with citation metrics where iCite (the National Institutes of Health citation-metrics service) carries them.

One row per: gene and paper
Key columns: route_key, pmid

Source: PubMed, NCBI/NLM; iCite, NIH Office of Portfolio Analysis

Columns 11

Trial-cited literature mentions columns
Column	Type	Unit	Description
route_key	text		The route key of the gene the paper names, the entry key for the biomarkers object type.
gene_symbol	text		The gene symbol.
pmid	text		The PubMed id.
evidence_type	text		The evidence type (a publication mention).
title	text		The paper's title.
journal_nlm_id	text		The journal's National Library of Medicine (NLM) id.
journal_title	text		The journal's title.
pub_year	integer	calendar year	The publication year.
citation_count	integer	citations	Citations, where iCite carries them (null is not measured, never zero).
relative_citation_ratio	numeric		The iCite relative citation ratio, where measured.
display_order	bigint		The page's fixed order: newest year first, then citations.

Companies publishing on a biomarker

pharma biomarkers get <id> biomarker-publishing-companies

The companies that publish on a biomarker, one row per biomarker gene and company, counted from paper-level evidence.

One row per: biomarker gene and company
Key columns: gene_symbol, publisher_company_id

Source: PubMed, NCBI/NLM

Columns 14

Companies publishing on a biomarker columns
Column	Type	Unit	Description
route_key	text		The biomarker route key of the gene the papers name (the gene symbol); the entry key for the biomarkers object type.
gene_symbol	text		The gene symbol.
publisher_company_id	text		Company level: the publisher's company.
publisher_company_name	text		Display name of the publisher's company.
publisher_group_id	text		Group level: the publisher's current ultimate parent company; a root company's group is itself.
publisher_group_name	text		Display name of the publisher's group.
n_publications	integer	papers	Papers that name the gene from the company's organizations (a consortium paper is excluded).
n_member_orgs	integer	organization records	The company's organizations the papers reach.
best_match_tier	text		Strongest affiliation match tier.
first_pub_year	integer	calendar year	Earliest publication year.
last_pub_year	integer	calendar year	Latest publication year.
supporting_pmids	text[]		A sample of the supporting PubMed ids.
supporting_pmids_truncated	boolean		True when the sample is shorter than the paper count.
n_papers_excluded_as_consortium	integer		Papers left out because they name too many organizations.

Literature-extracted relations

pharma biomarkers get <id> biomarker-relations

Automated PubTator relation labels between a biomarker and a related gene, drug or condition, one row per related entity, source relation label and paper.

One row per: biomarker, related entity, source relation label and paper
Key columns: biomarker_id, related_entity_kind, related_entity_id, relation_type, pmid

Source: PubMed, NCBI/NLM

Columns 19

Literature-extracted relations columns
Column	Type	Unit	Description
route_key	text		The biomarker's own route key, the entry key for the biomarkers object type (the gene symbol for a gene, the variant key for a protein variant).
biomarker_id	text		The biomarker's key.
biomarker_kind	text		Whether the row describes a gene or a protein variant.
gene_symbol	text		The gene symbol.
amino_acid_change	text		The protein change, for a variant.
related_entity_kind	text		The kind of the related entity (gene, drug or condition).
related_entity_id	text		The related entity's key in its own vocabulary (a gene symbol, a drug id such as unii:..., or a condition key).
related_display_name	text		The related entity's name.
relation_type	text		The source's relation label, as the source states it.
pmid	text		The PubMed id of the paper the relation was extracted from.
title	text		The paper's title.
journal_nlm_id	text		The journal's National Library of Medicine (NLM) id.
journal_title	text		The journal's title.
pub_year	integer	calendar year	The paper's publication year.
n_source_assertions	bigint	assertions	Source assertions of this relation in the paper.
n_relation_papers	bigint	papers	Papers that carry this biomarker, related entity and relation label.
evidence_type	text		The evidence type (a text-mined relation, never a clinical claim).
source	text		The source of the evidence.
display_order	bigint		The order the web page lists the relation in within its kind.

Human sample screening coverage (GDC)

pharma biomarkers get <id> biomarker-sample-coverage

How each protein variant of a gene matched the somatic-mutation catalogue of the National Cancer Institute Genomic Data Commons (GDC), one row per variant and data release, so a variant with no exact match or several matches is a row with its status.

One row per: protein variant and GDC data release
Key columns: variant_biomarker_id, gdc_data_release

Source: NCI Genomic Data Commons

Columns 10

Human sample screening coverage (GDC) columns
Column	Type	Unit	Description
route_key	text		The route key of the gene the variants belong to, the entry key for the biomarkers object type.
gene_symbol	text		The gene symbol.
variant_biomarker_id	text		The variant's own biomarker key.
variant_route_key	text		The variant's own route key (the id its web page uses).
amino_acid_change	text		The protein change, for example p.V600E.
gdc_data_release	text		The Genomic Data Commons data release the match was made against.
normalization_status	text		How the variant matched: resolved_single_ssm, no_exact_ssm, multiple_exact_ssms or source_error.
match_count	integer	mutations	Somatic mutations in the catalogue that encode the same protein change.
resolution_reason	text		The reason for the status, in words.
measured_project_count	bigint	projects	Research projects with an observed frequency for the variant in biomarker_sample_prevalence.

Human sample screening reference (GDC cohorts)

pharma biomarkers get <id> biomarker-sample-prevalence

Exact protein-variant observations in named research cohorts of the National Cancer Institute Genomic Data Commons (GDC), one row per variant, cohort and data release. A screening reference for named cohorts.

One row per: protein variant, GDC research cohort and data release
Key columns: variant_biomarker_id, gdc_project_id, gdc_data_release

Source: NCI Genomic Data Commons

Columns 20

Human sample screening reference (GDC cohorts) columns
Column	Type	Unit	Description
route_key	text		The route key of the gene the variants belong to, the entry key for the biomarkers object type.
gene_symbol	text		The gene symbol.
variant_biomarker_id	text		The variant's own biomarker key.
variant_route_key	text		The variant's own route key (the id its web page uses).
amino_acid_change	text		The protein change, for example p.V600E.
gdc_ssm_id	text		The identifier of the somatic mutation in the Genomic Data Commons.
gdc_project_id	text		The Genomic Data Commons research project (cohort) the counts come from.
gdc_project_name	text		The name of the research project.
condition_id	text		The condition key (a MeSH, Medical Subject Headings, descriptor id) the project's disease maps to, where one is mapped.
condition_name	text		The mapped condition's MeSH heading.
source_disease_types	text[]		The disease types the source states for the project.
source_primary_sites	text[]		The primary sites the source states for the project.
affected_case_count	bigint	cases	Cases in the cohort with the exact variant.
ssm_profiled_case_count	bigint	cases	Cases in the cohort profiled for somatic mutations, the denominator of the observed frequency.
all_case_count	bigint	cases	All cases in the project.
observed_frequency	numeric	fraction	Affected cases over mutation-profiled cases in this cohort.
frequency_ci95_low	numeric	fraction	Lower bound of the 95 percent confidence interval of the observed frequency.
frequency_ci95_high	numeric	fraction	Upper bound of the 95 percent confidence interval of the observed frequency.
gdc_data_release	text		The Genomic Data Commons data release the counts come from.
claim_type	text		What the figure states; an observed frequency in a named cohort.

Biomarker validation ladder

pharma biomarkers get <id> biomarker-validation

The validation ladder of a gene: which organizations can supply evidence toward running its assay, in what role, at what tier and citing what, across six kinds of evidence (companion diagnostic authorization, trial endpoint, trial eligibility, trial specimen collection, trial text mention and ClinVar clinical testing).

One row per: evidence assertion on a gene
Key columns: biomarker_validation_id

Source: ClinicalTrials.gov via AACT, CTTI (CC BY); US FDA; ClinVar, NCBI/NLM

Columns 27

Biomarker validation ladder columns
Column	Type	Description
biomarker_validation_id	text	The evidence assertion id.
route_key	text	The biomarker's route key, the entry key for the biomarkers object type; for a gene it is the gene symbol.
gene_symbol	text	The gene symbol (HGNC, the HUGO Gene Nomenclature Committee).
biomarker_id	text	The biomarker key.
biomarker_display_name	text	The biomarker's display name.
biomarker_kind	text	The kind of biomarker the evidence is filed against.
organization_name	text	The organization that can supply the evidence, as the source names it (null when the source names none that resolved).
organization_org_id	text	Legal-entity level: the organization record (null when unresolved).
organization_company_id	text	Company level: the organization's company (null when unresolved).
organization_company_name	text	Display name of the organization's company.
organization_group_id	text	Group level: the organization's current ultimate parent; a root's group is itself.
organization_group_name	text	Display name of the organization's group.
organization_role	text	What the organization is to the evidence: lead_sponsor, collaborator, contract_vendor, assay_manufacturer, qualification_submitter, testing_lab or publishing_org.
organization_match_tier	text	How the organization name matched an organization record.
tier	integer	The rung on the validation ladder, 1 to 4. A rung is a kind of evidence, never a score: rows are not ranked across organizations or evidence types.
tier_label	text	The rung's name, for example fda_authorized_companion_diagnostic or named_in_inclusion_criteria.
evidence_type	text	The evidence lane: fda_bqp_qualification, fda_cdx_authorization, aact_endpoint_role, aact_eligibility_section, aact_biospecimen, trial_mention or clinvar_clinical_testing.
evidence_count	integer	Sibling rows sharing this biomarker, organization and role. Not the number of source records behind a ClinVar row (clinvar_scv_count).
evidence_ref	text	The source reference the row cites.
evidence_ref_kind	text	What kind of reference evidence_ref is.
trial_id	text	The trial key (an NCT id) when the evidence is a trial; null otherwise.
citation_url	text	A link to the cited record.
citation_verified	boolean	False for the FDA Biomarker Qualification Program arm, whose captured links are known to go stale; true otherwise. A link marked false may not resolve.
evidence_snippet	text	The text span the evidence rests on, where the source gives one.
biomarker_role	text	The biomarker's role in the evidence, where the source states it.
is_surrogate_endpoint_claim	boolean	True when the evidence is a claim that the biomarker is a surrogate endpoint.
clinvar_scv_count	integer	For a ClinVar row, the number of ClinVar submission records the row collapses; null otherwise.

Protein variant mentions

pharma biomarkers get <id> biomarker-variant-mentions

Exact protein variants of a gene that papers in the trial-cited corpus name, with the paper counts and sample citations.

One row per: protein variant biomarker with literature mentions
Key columns: variant_biomarker_id

Source: PubMed, NCBI/NLM

Columns 14

Protein variant mentions columns
Column	Type	Unit	Description
route_key	text		The route key of the gene the variants belong to, the entry key for the biomarkers object type.
gene_symbol	text		The gene symbol.
variant_biomarker_id	text		The variant's own biomarker key.
variant_route_key	text		The variant's own route key (the id its web page uses).
display_name	text		The variant's display name.
amino_acid_change	text		The protein change, for example V600E.
biomarker_kind	text		The kind of biomarker the row describes (a protein variant).
evidence_type	text		The evidence type (a literature mention, never an actionability claim).
source	text		The source of the evidence.
n_papers	bigint	papers	Distinct papers that name the variant.
first_publication_year	integer	calendar year	Earliest publication year.
last_publication_year	integer	calendar year	Latest publication year.
sample_pmids	text[]		Up to five sample PubMed ids, newest first.
sample_citations	text[]		Up to five sample citations, newest first.

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