Genomic Variant Queries¶

For querying of genomic variations Beacon v2 builds on and extends the options provided by earlier versions.

Beacon Sequence Queries¶

Sequence Queries query for the existence of a specified sequence at a given genomic position. Such queries correspond to the original Beacon queries and are used to match short, precisely defined genomic variants such as SNVs and INDELs.

Parameters¶

referenceName
start (single value)
alternateBases
referenceBases

Example: EIF4A1 Single Base Mutation¶

This is an example for a single base mutation (G>A) at a specific position (GRCh38 chromosome 17 7577120) in the EIF4A1 eukaryotic translation initiation factor 4A1.

Beacon v2 GETBeacon v2 POSTBeacon v1Beacon v0.3

?referenceName=NC_000017.11&start=7577120&referenceBases=G&alternateBases=A

Optional¶

datasetIds=__some-dataset-ids__
filters ...

{
    "$schema":"beaconRequestBody.json",
    "meta": {
        "apiVersion": "2.0",
        "requestedSchemas": [
            {
                "entityType": "genomicVariation",
                "schema:": "https://raw.githubusercontent.com/ga4gh-beacon/beacon-v2/main/models/json/beacon-v2-default-model/genomicVariations/defaultSchema.json"
            }
        ]
    },
    "query": {
        "requestParameters": {
            "g_variant": {
                "referenceName": "NC_000017.11",
                "start": [7577120],
                "referenceBases": "G",
                "alternateBases": "A"
            }
        }
    },
    "requestedGranularity": "record",
    "pagination": {
        "skip": 0,
        "limit": 5
    }
}

There are optional parameters [datasetIds, filters ...] and also the option to specify the response type (through requestedGranularity) and returned data format (requestedSchemas). Please follow this up in the framework documentation.

?assemblyId=GRCh38&referenceName=17&start=7577120&referenceBases=G&alternateBases=A

Optional¶

datasetIds=__some-dataset-ids__

?ref=GRCh38&chrom=17&pos=7577121&referenceAllele=C&allele=A

Optional¶

beacon=__some-beacon-id__

Before Beacon v0.4 a 1-based coordinate system was being used.

Beacon Range Queries¶

Beacon Range Queries are supposed to return matches of any variant with at least partial overlap of the sequence range specified by reference_name, start and end parameters.

Beacon Range Query Schema

Parameters¶

referenceName
start (single value)
end (single value)
optional
- variantType OR alternateBases OR aminoacidChange
- variantMinLength
- variantMaxLength

Use of start and end

Range queries require the use of single start and end parameters, in contrast to Bracket Queries.

Example: Any variant affecting EIF4A1¶

Beacon v2 GETBeacon v2 POSTBeacon v1Beacon v0.3

?assemblyId=GRCh38&referenceName=17&start=7572837&end=7578641

{
    "$schema":"https://raw.githubusercontent.com/ga4gh-beacon/beacon-v2/main/framework/json/requests/beaconRequestBody.json",
    "meta": {
        "apiVersion": "2.0",
        "requestedSchemas": [
            {
                "entityType": "genomicVariation",
                "schema:": "https://raw.githubusercontent.com/ga4gh-beacon/beacon-v2/main/models/json/beacon-v2-default-model/genomicVariations/defaultSchema.json"
            }
        ]
    },
    "query": {
        "requestParameters": {
            "g_variant":
                "referenceName": "NC_000017.11",
                "start": [ 7572837 ],
                "end": [ 7578641 ]
            }
        }
    },
    "requestedGranularity": "record",
    "pagination": {
        "skip": 0,
        "limit": 5
    }
}

Range Queries are new to Beacon v2

Beacon GeneId Queries¶

GeneId Queries are in essence a variation of Range Queries in which the coordinates are replaced by the HGNC gene symbol. It is left to the implementation if the matching is done on variants annotated for the gene symbol or if a positional translation is being applied.

Beacon Gene Query Schema

Parameters¶

geneId
optional
- variantType OR alternateBases OR aminoacidChange
- variantMinLength
- variantMaxLength

Beacon v2 GET for geneId (deletion CNV)Beacon v2 POST for geneId (deletion CNV)

?geneId=EIF4A1&variantMaxLength=1000000&variantType=DEL

{
    "$schema":"https://raw.githubusercontent.com/ga4gh-beacon/beacon-v2/main/framework/json/requests/beaconRequestBody.json",
    "meta": {
        "apiVersion": "2.0",
        "requestedSchemas": [
            {
                "entityType": "genomicVariation",
                "schema:": "https://raw.githubusercontent.com/ga4gh-beacon/beacon-v2/main/models/json/beacon-v2-default-model/genomicVariations/defaultSchema.json"
            }
        ]
    },
    "query": {
        "requestParameters": {
            "g_variant":
                "geneId": "EIF4A1",
                "variantType": "EFO:0030067"
            }
        }
    },
    "requestedGranularity": "record",
    "pagination": {
        "skip": 0,
        "limit": 5
    }
}

Beacon Bracket Queries¶

Bracket Queries allow the specification of sequence ranges for both start and end positions of a genomic variation. The typical example here is the query for similar structural variants - particularly CNVs - affecting a genomic region but potentially differing in their exact base extents.

Beacon Bracket Query Schema

Parameters¶

referenceName
start (min) and start (max) - i.e. 2 start parameters
end (min) and end (max) - i.e. 2 end parameters
variantType (optional)

Use of start and end

Bracket queries require the use of two start and end parameters, in contrast to Range Queries.

List Parameters in GET Requests

Since the direct interpretation of list parameters in queries is not supported by some server environments (e.g. PHP, GO…), list parameters such as start and end should be provided as comma-concatenated strings when using them in GET requests.

Example: CNV Query - TP53 Deletion Query by Coordinates¶

The following example shows a "bracket query" for focal deletions of the TP53 gene locus:

The start of the deletion has to occurr anywhere from approx. 2.5Mb 5' of the CDR start to just before the end of the CDR.
The end of the matched CNVs has to be anywhere from the start of the gene locus to approx. 2.5Mb 3' of its end.

This leads to matching of deletion CNVs which have at least some base overlap with the gene locus but are not larger than approx. 5Mb (operational definitions of focality vary between 1 and 5Mb).

Beacon v2 GETBeacon v2 POSTBeacon v1Beacon v0.3

?datasetIds=TEST&referenceName=NC_000017.11&variantType=DEL&start=5000000,7676592&end=7669607,10000000

Optional¶

datasetIds=__some-dataset-ids__
filters ...

{
    "$schema":"https://raw.githubusercontent.com/ga4gh-beacon/beacon-v2/main/framework/json/requests/beaconRequestBody.json",
    "meta": {
        "apiVersion": "2.0",
        "requestedSchemas": [
            {
                "entityType": "genomicVariation",
                "schema:": "https://raw.githubusercontent.com/ga4gh-beacon/beacon-v2/main/models/json/beacon-v2-default-model/genomicVariations/defaultSchema.json"
            }
        ]
    },
    "query": {
        "requestParameters": {
            "g_variant": {
                "referenceName": "NC_000017.11",
                "start": [ 5000000, 7676592 ],
                "end": [ 7669607, 10000000 ],
                "variantType": "DEL"
            }
        }
    },
    "requestedGranularity": "record",
    "pagination": {
        "skip": 0,
        "limit": 5
    }
}

There are optional parameters [datasetIds, filters ...] and also the option to specify the response type (through requestedGranularity) and returned data format (requestedSchemas). Please follow this up in the framework documentation.

?assemblyId=GRCh38&referenceName=17&variantType=DEL&start=5000000,7676592&end=7669607,10000000

Optional¶

datasetIds=__some-dataset-ids__

CNV query options were only implemented with Beacon v0.4, based on Beacon⁺ prototyping.

Genomic Allele Query (Short Form)¶

When available variants can be identified through their genomic HGVS short form.

Beacon v2 GET

?genomicAlleleShortForm=NM_004006.2:c.4375C>T

Aminoacid Change Query¶

Annotated variants can potentiallyqueried using the single amino acid replacement format. The aminoacidChange parameter may be combined with e.g. a geneId to increase specificity

Beacon v2 GET

?aminoacidChange=V600E&geneId=BRAF

`variantType` Parameter Interpretation¶

The variantType parameter is essential for scoping queries beyond precise sequence queries. While versions of Beacon before v2 had demonstrated the use of a few, VCF derived values (particularly for CNV queries using DUP or DEL), the relation of these values to underlying genomic variations had not been precisely defined.

Implementation of variantType in Beacon Instances

The current Beacon query model does not limit the use of values for variantType since at this time no single specification provides unanimous definitions of genomic variation categories.

Future variantType parameter use

While for legacy reasons and widespread use of VCFs as input source Beacon v2 documents the use of VCF-like terms, in principle other variant terms can be used (though with possibly negative implications in federated settings). The field of structural genomic variant annotations is rapidly developing, with more specific terms now becoming available e.g. through the Experimental Factor Ontology or the GA4GH Variant Representation Standard VRS (which ligns with the main EFO terms).

CNV Term Use Comparison in Computational (File/Schema) Formats¶

This table is maintained in parallel with the hCNV community documentation.

EFO	Beacon	VCF	SO	GA4GH VRS ⇒ VRS proposal¹	Notes
`EFO:0030070` copy number gain	`DUP`² or `EFO:0030070`	`DUP` `SVCLAIM=D`³	`SO:0001742` copy_number_gain	`low-level gain` (implicit) ⇒ `EFO:0030070` copy number gain	a sequence alteration whereby the copy number of a given genomic region is greater than the reference sequence
`EFO:0030071` low-level copy number gain	`DUP`² or `EFO:0030071`	`DUP` `SVCLAIM=D`³	`SO:0001742` copy_number_gain	`low-level gain` ⇒ `EFO:0030071` low-level copy number gain
`EFO:0030072` high-level copy number gain	`DUP`² or `EFO:0030072`	`DUP` `SVCLAIM=D`³	`SO:0001742` copy_number_gain	`high-level gain` ⇒ `EFO:0030072` high-level copy number gain	commonly but not consistently used for >=5 copies on a bi-allelic genome region
`EFO:0030073` focal genome amplification	`DUP`² or `EFO:0030073`	`DUP` `SVCLAIM=D`³	`SO:0001742` copy_number_gain	`high-level gain` ⇒ `EFO:0030073` focal genome amplification	commonly but not consistently used for >=5 copies on a bi-allelic genome region, of limited size (operationally max. 1-5Mb)
`EFO:0030067` copy number loss	`DEL`² or `EFO:0030067`	`DEL` `SVCLAIM=D`³	`SO:0001743` copy_number_loss	`partial loss` (implicit) ⇒ `EFO:0030067` copy number loss	a sequence alteration whereby the copy number of a given genomic region is smaller than the reference sequence
`EFO:0030068` low-level copy number loss	`DEL`² or `EFO:0030068`	`DEL` `SVCLAIM=D`³	`SO:0001743` copy_number_loss	`partial loss` ⇒ `EFO:0030068` low-level copy number loss
`EFO:0020073` high-level copy number loss	`DEL`² or `EFO:0020073`	`DEL` `SVCLAIM=D`³	`SO:0001743` copy_number_loss	`partial loss` ⇒ `EFO:0020073` high-level copy number loss	a loss of several copies; also used in cases where a complete genomic deletion cannot be asserted
`EFO:0030069` complete genomic deletion	`DEL`² or `EFO:0030069`	`DEL` `SVCLAIM=D`³	`SO:0001743` copy_number_loss	`complete loss` ⇒ `EFO:0030069` complete genomic deletion	complete genomic deletion (e.g. homozygous deletion on a bi-allelic genome region)

Last updated 2023-03-22 by @mbaudis (EFO:0020073)¶

updated 2023-03-20 by @mbaudis (VRS proposal)¶

Query Parameter Change Log¶

Beacon v2¶

use of sequence reference id's which obviate the need for a assemblyId parameter
range queries
- with specified single start and end parameters a query should match any vatiant with partial or complete overlap with this sequence range
- additional parameters (e.g. referenceBases, alternateBases, variantType...) may be used to scope the range query
query by aminoacidChange
query by geneId
variantMinLength, variantMaxLength

Beacon v1 (based on v0.4)¶

switch to 0-based interbase coordinates for the API with 1-based coordinates recommended for query forms
- this represents the common GA4GH usage and the practice e.g. of the UCSC genome browser
introduction of bracketed queries
- specification of intervals for start and end positions when querying multi-base variants allows for "fuzzy" CNV queries
support of a variantType parameter to specify e.g. CNV queries (DUP, DEL)
- variantType is not required for precise queries with specified referenceBases and alternateBases

The VRS annotations refer to the status at v1.2 (2022). The GA4GH VRS team is currently (Spring 2023) preparing an updated specification which will introduce the new class CopyNumberChange (discussion...) with the use of the EFO terms (including a new term for high level deletion (EFO:0020073) in the April 2023 EFO release). ↩
While the use of VCF derived (DUP, DEL) values had been introduced with beacon v1, usage of these terms has always been a recommendation rather than an integral part of the API. We now encourage the support of more specific terms (particularly EFO) by Beacon developers. As example, the Progentix Beacon API uses EFO terms but provides an internal term expansion for legacy DUP, DEL support. ↩↩↩↩↩↩↩↩
VCFv4.4 introduces an SVCLAIM field to disambiguate between in situ events (such as tandem duplications; known adjacency/ break junction: SVCLAIM=J) and events where e.g. only the change in abundance / read depth (SVCLAIM=D) has been determined. Both J and D flags can be combined. ↩↩↩↩↩↩↩↩

Genomic Variant Queries¶

Beacon Sequence Queries¶

Parameters¶

Example: EIF4A1 Single Base Mutation¶

Optional¶

Optional¶

Optional¶

Beacon Range Queries¶

Parameters¶

Example: Any variant affecting EIF4A1¶

Beacon GeneId Queries¶

Parameters¶

Beacon Bracket Queries¶

Parameters¶

Example: CNV Query - TP53 Deletion Query by Coordinates¶

Optional¶

Optional¶

Genomic Allele Query (Short Form)¶

Aminoacid Change Query¶

variantType Parameter Interpretation¶

CNV Term Use Comparison in Computational (File/Schema) Formats¶

Last updated 2023-03-22 by @mbaudis (EFO:0020073)¶

updated 2023-03-20 by @mbaudis (VRS proposal)¶

Query Parameter Change Log¶

Beacon v2¶

Beacon v1 (based on v0.4)¶

`variantType` Parameter Interpretation¶