Package 'otargen'

Description

This function queries the Open Targets GraphQL API to retrieve adverse events data for a specified drug.

Usage

adverseEventsQuery(chemblId, index = 0, size = 10)

Arguments

Value

Returns a tibble containing adverse events data for the specified drug.

Examples

## Not run: 
result <- adverseEventsQuery(chemblId = "CHEMBL1016", size = 10)
result <- adverseEventsQuery(chemblId = "CHEMBL1016", index = 0, size = 10)

## End(Not run)

Description

This function queries the Open Targets GraphQL API to retrieve ChEMBL evidence data for a specified gene and disease.

Usage

chemblQuery(ensemblId, efoId, cursor = NULL, size = 10)

Arguments

Value

Returns a tibble containing ChEMBL evidence data for the specified gene and disease.

Examples

## Not run: 
result <- chemblQuery(ensemblId = "ENSG00000080815", efoId = 
"MONDO_0004975",
 size = 10)
result <- chemblQuery(ensemblId = "ENSG00000080815", efoId = 
"MONDO_0004975",
 cursor = NULL, size = 10)

## End(Not run)

Description

This function queries the Open Targets GraphQL API to retrieve ClinVar evidence data for a specified gene and disease.

Usage

clinVarQuery(ensemblId, efoId, cursor = NULL, size = 10)

Arguments

Value

Returns a tibble containing ClinVar evidence data for the specified gene and disease.

Examples

## Not run: 
result <- clinVarQuery(ensemblId = "ENSG00000080815", efoId = 
"MONDO_0004975", size = 10)
result <- clinVarQuery(ensemblId = "ENSG00000080815", efoId = 
"MONDO_0004975", cursor = NULL, size = 10)

## End(Not run)

Description

This function queries the Open Targets GraphQL API to retrieve comparative genomics data for a specified gene.

Usage

compGenomicsQuery(ensemblId)

Arguments

Value

Returns a data frame containing comparative genomics data for the specified gene.

Examples

## Not run: 
result <- compGenomicsQuery(ensemblId = "ENSG00000169174")

## End(Not run)

Description

This function queries the Open Targets GraphQL API to retrieve DepMap essentiality data for a specified gene.

Usage

depMapQuery(ensgId)

Arguments

Value

Returns a tibble containing DepMap essentiality data for the specified gene.

Examples

## Not run: 
result <- depMapQuery(ensgId = "ENSG00000141510")

## End(Not run)

Description

This function queries the Open Targets GraphQL API to retrieve Europe PMC evidence data for a specified gene and disease.

Usage

europePMCQuery(ensemblId, efoId, cursor = NULL, size = 50)

Arguments

Value

Returns a tibble containing Europe PMC evidence data for the specified gene and disease.

Examples

## Not run: 
result <- europePMCQuery(ensemblId = "ENSG00000080815",
 efoId = "MONDO_0004975", size = 50)
result <- europePMCQuery(ensemblId = "ENSG00000080815", 
efoId = "MONDO_0004975", cursor = NULL, size = 50)

## End(Not run)

Description

This function queries the Open Targets GraphQL API to retrieve gene burden evidence data for a specified gene and disease.

Usage

geneBurdenQuery(ensemblId, efoId, size = 3500)

Arguments

Value

Returns a tibble containing gene burden evidence data for the specified gene and disease.

Examples

## Not run: 
result <- geneBurdenQuery(ensemblId = "ENSG00000137642", efoId = 
"MONDO_0004975", size = 3500)

## End(Not run)

Description

This function queries the Open Targets GraphQL API to retrieve gene ontology data for a specified gene.

Usage

geneOntologyQuery(ensgId)

Arguments

Value

Returns a tibble containing gene ontology data for the specified gene.

Examples

## Not run: 
result <- geneOntologyQuery(ensgId = "ENSG00000141510")

## End(Not run)

Description

This function queries the Open Targets Platform GraphQL API to retrieve genetic constraint data for a specified gene, such as pLI or LOEUF scores.

Usage

geneticConstraintQuery(ensgId)

Arguments

Value

Returns a tibble containing genetic constraint data for the specified gene.

Examples

## Not run: 
result <- geneticConstraintQuery(ensgId = "ENSG00000141510")

## End(Not run)

Description

This function queries the Open Targets GraphQL API to retrieve Genomics England evidence data for a specified gene and disease.

Usage

genomicsEnglandQuery(ensemblId, efoId, size = 3500)

Arguments

Value

Returns a tibble containing Genomics England evidence data for the specified gene and disease.

Examples

## Not run: 
result <- genomicsEnglandQuery(ensemblId = "ENSG00000080815", efoId = 
"MONDO_0004975", size = 3500)

## End(Not run)

Description

This function retrieves colocalisation data for a specific study locus from a GWAS study with other GWAS studies. It returns a data frame of the studies that colocalise with the input study locus, including details on the study, reported trait, index variant, and calculated colocalisation method outputs.

Usage

gwasColocalisation(study_locus_id, size = 500, index = 0)

Arguments

Value

Returns a data frame of the studies that colocalise with the input study locus. The table consists of the following data structure:

• study.studyId: Character vector. Study identifier.

• study.traitReported: Character vector. Reported trait associated with the colocalisation.

• study.projectId: Character vector. Project identifier for the study.

• study.publicationFirstAuthor: Character vector. First author of the publication.

• indexVariant.id: Character vector. Index variant identifier.

• indexVariant.position: Integer vector. Index variant position.

• indexVariant.chromosome: Character vector. Index variant chromosome.

• indexVariant.referenceAllele: Character vector. Reference allele of the variant.

• indexVariant.alternateAllele: Character vector. Alternate allele of the variant.

• pValueMantissa: Numeric vector. Mantissa of the p-value for the colocalisation.

• pValueExponent: Integer vector. Exponent of the p-value for the colocalisation.

• numberColocalisingVariants: Integer vector. Number of colocalising variants.

• colocalisationMethod: Character vector. Method used for colocalisation analysis.

• h3: Numeric vector. H3 value associated with the colocalisation.

• h4: Numeric vector. H4 value associated with the colocalisation.

• clpp: Numeric vector. Colocalisation posterior probability.

• betaRatioSignAverage: Numeric vector. Average sign of the beta ratio.

References

Giambartolomei, Claudia et al. “Bayesian test for colocalisation between pairs of genetic association studies using summary statistics.” PLoS genetics vol. 10,5 e1004383. 15 May. 2014, doi:10.1371/journal.pgen.1004383

Examples

## Not run: 
colocalisation_data <- gwasColocalisation(study_locus_id = "5a86bfd40d2ebecf6ce97bbe8a737512",
 size = 500, index = 0)

## End(Not run)

Description

Provided with a study ID and a lead variant ID, this function returns a data frame consisting of all the associated credible set tag variants with the corresponding statistical data.

Usage

gwasCredibleSet(study_id, variant_id)

Arguments

Value

Returns a data frame of results from the credible set of variants for a specific lead variant with the following columns:

• tagVariant.id: Data frame. A table of IDs of the tag variant.

• tagVariant.rsId: Character vector. rsID of the tag variant.

• beta: Numeric. Beta value.

• postProb: Numeric. Posterior probability.

• pval: Numeric. P-value.

• se: Numeric. Standard error.

• MultisignalMethod: Character vector. Multisignal method.

• logABF: Numeric. Logarithm of approximate Bayes factor.

• is95: Logical. Indicates if the variant has a 95

• is99: Logical. Indicates if the variant has a 99

Examples

## Not run: 
result <- gwasCredibleSet(study_id="GCST90002357", 
variant_id="1_154119580_C_A")
result <- gwasCredibleSet(study_id="GCST90002357", variant_id="rs2494663")

## End(Not run)

Description

This function queries the Open Targets Platform GraphQL API to retrieve GWAS credible sets evidence data for a specified target gene and disease.

Usage

gwasCredibleSetsQuery(ensemblId, efoId, size = 500)

Arguments

Value

A tibble with credible set evidence or NULL if no data found.

Examples

## Not run: 
  result <- gwasCredibleSetsQuery(
    ensemblId = "ENSG00000169174",
    efoId = "EFO_0004911",
    size = 5
  )
  print(result)

## End(Not run)

Description

This function queries the Open Targets GraphQL API to retrieve cancer hallmarks data for a specified gene.

Usage

hallmarksQuery(ensgId)

Arguments

Value

Returns a tibble containing cancer hallmarks data for the specified gene.

Examples

## Not run: 
result <- hallmarksQuery(ensgId = "ENSG00000141510")

## End(Not run)

Description

This function queries the Open Targets GraphQL API to retrieve indications data for a specified drug.

Usage

indicationsQuery(chemblId)

Arguments

Value

Returns a tibble containing indications data for the specified drug.

Examples

## Not run: 
result <- indicationsQuery(chemblId = "CHEMBL1016")

## End(Not run)

Description

This function queries the Open Targets GraphQL API to retrieve molecular interaction data for a specified gene.

Usage

interactionsQuery(ensgId, sourceDatabase = NULL, index = 0, size = 10)

Arguments

Value

Returns a tibble containing interactions data for the specified gene.

Examples

## Not run: 
result <- interactionsQuery(ensgId = "ENSG00000141510",
 sourceDatabase = "intact", size = 10)
result <- interactionsQuery(ensgId = "ENSG00000141510",
 sourceDatabase = "intact", index = 0, size = 10)

## End(Not run)

Description

This function queries the Open Targets GraphQL API to retrieve indications and clinical report data for a specified drug.

Usage

knownDrugsChemblQuery(chemblId)

Arguments

Value

Returns a tibble containing indications data for the specified drug.

Examples

## Not run: 
result <- knownDrugsChemblQuery(chemblId = "CHEMBL1016")

## End(Not run)

Description

This function queries the Open Targets GraphQL API to retrieve drug and clinical candidate data for a specified gene.

Usage

knownDrugsGeneQuery(ensgId)

Arguments

Value

Returns a data frame containing drug and clinical candidate data for the specified gene.

Examples

## Not run: 
result <- knownDrugsGeneQuery(ensgId = "ENSG00000169174")

## End(Not run)

Description

This function queries the Open Targets GraphQL API to retrieve locus-to-gene prediction data for a specified study locus.

Usage

locus2GeneQuery(studyLocusId)

Arguments

Value

Returns a tibble containing locus-to-gene prediction data for the specified study locus.

Examples

## Not run: 
result <- locus2GeneQuery(studyLocusId = "fa375739ca2a6b825ce5cc69d117e84b")

## End(Not run)

Description

This function queries the Open Targets GraphQL API to retrieve mechanisms of action data for a specified drug.

Usage

mechanismsOfActionQuery(chemblId)

Arguments

Value

Returns a tibble containing mechanisms of action data for the specified drug.

Examples

## Not run: 
result <- mechanismsOfActionQuery(chemblId = "CHEMBL1016")

## End(Not run)

Description

This function queries the Open Targets GraphQL API to retrieve mouse phenotypes data for a specified gene.

Usage

mousePhenotypesQuery(ensemblId)

Arguments

Value

Returns a data frame containing mouse phenotypes data for the specified gene.

Examples

## Not run: 
result <- mousePhenotypesQuery(ensemblId = "ENSG00000169174")

## End(Not run)

Description

This function queries the Open Targets GraphQL API to retrieve Orphanet evidence data for a specified gene and disease.

Usage

orphanetQuery(ensemblId, efoId, size = 3500)

Arguments

Value

Returns a tibble containing Orphanet evidence data for the specified gene and disease.

Examples

## Not run: 
result <- orphanetQuery(ensemblId = "ENSG00000080815", efoId = 
"MONDO_0004975", size = 3500)

## End(Not run)

Description

For an input study ID and a list of other study IDs, this function returns two elements. One contains the overlap information in a table format, and the other element is the variant intersection set, representing an overlap between two variants of the two given studies.

Usage

overlapInfoForStudy(study_id, study_ids = list())

Arguments

Value

A list containing a data frame of overlap information and the variant intersection set. The overlap information table (overlap_info) consists of the following columns:

• studyId: Character vector. Study ID.

• traitReported: Character vector. Reported trait.

• traitCategory: Character vector. Trait category.

• variantIdA: Character vector. Variant ID from study A.

• variantIdB: Character vector. Variant ID from study B.

• overlapAB: Integer vector. Number of overlaps between variants A and B.

• distinctA: Integer vector. Number of distinct variants in study A.

• distinctB: Integer vector. Number of distinct variants in study B.

• study.studyId: Character vector. Study ID from study list.

• study.traitReported: Character vector. Reported trait from study list.

• study.traitCategory: Character vector. Trait category from study list.

The variant intersection set (variant_intersection_set) is a character vector representing the intersection of variants.

Examples

## Not run: 
result <- overlapInfoForStudy(study_id = "GCST90002357",
 study_ids = list("GCST90025975", "GCST90025962"))

## End(Not run)

Description

This function queries the Open Targets GraphQL API to retrieve pathways data for a specified gene.

Usage

pathwaysQuery(ensgId)

Arguments

Value

Returns a tibble containing pathways data for the specified gene.

Examples

## Not run: 
result <- pathwaysQuery(ensgId = "ENSG00000105397")

## End(Not run)

Description

This function queries the Open Targets GraphQL API to retrieve pharmacogenomics data for a specified drug.

Usage

pharmacogenomicsChemblQuery(chemblId)

Arguments

Value

Returns a tibble containing pharmacogenomics data for the specified drug.

Examples

## Not run: 
result <- pharmacogenomicsChemblQuery(chemblId = "CHEMBL1016")

## End(Not run)

Description

This function queries the Open Targets GraphQL API to retrieve pharmacogenomics data for a specified gene.

Usage

pharmacogenomicsGeneQuery(ensgId)

Arguments

Value

Returns a tibble containing pharmacogenomics data for the specified gene.

Examples

## Not run: 
result <- pharmacogenomicsGeneQuery(ensgId = "ENSG00000141510")

## End(Not run)

Description

This function queries the Open Targets GraphQL API to retrieve pharmacogenomics data for a specified variant.

Usage

pharmacogenomicsVariantQuery(variantId)

Arguments

Value

Returns a tibble containing pharmacogenomics data for the specified variant.

Examples

## Not run: 
result <- pharmacogenomicsVariantQuery(variantId = "12_111446804_T_C")

## End(Not run)

Description

Displays the top adverse events ranked by log-likelihood ratio (logLR) with a dashed reference line at the critical value threshold.

Usage

plot_adverse_events(df, top_n = 20)

Arguments

Value

A ggplot object.

Examples

## Not run: 
ae <- adverseEventsQuery(chemblId = "CHEMBL941")
plot_adverse_events(ae)

## End(Not run)

Description

Scatter plot of the H4 posterior probability (shared causal variant) against the number of colocalising variants, with labels for each colocalising trait and a threshold reference line at H4 = 0.8.

Usage

plot_colocalisation(df, h4_threshold = 0.8)

Arguments

Value

A ggplot object.

Examples

## Not run: 
coloc <- gwasColocalisation(study_locus_id = "5a86bfd40d2ebecf6ce97bbe8a737512")
plot_colocalisation(coloc)

## End(Not run)

Description

Faceted horizontal bar chart showing disease indications grouped by clinical trial stage. Each stage gets its own panel listing the individual disease names.

Usage

plot_indications(df, top_n = 10)

Arguments

Value

A ggplot object.

Examples

## Not run: 
ind <- indicationsQuery(chemblId = "CHEMBL941")
plot_indications(ind)

## End(Not run)

Description

Draws a circular network layout of molecular interaction partners with edge thickness proportional to the interaction confidence score.

Usage

plot_interactions(df, top_n = 20)

Arguments

Value

A ggplot object.

Examples

## Not run: 
int <- interactionsQuery(ensgId = "ENSG00000141510",
  sourceDatabase = "intact", size = 25)
plot_interactions(int)

## End(Not run)

Description

Displays candidate genes ranked by their L2G score as a horizontal bar chart with a color gradient.

Usage

plot_l2g(df, top_n = 15)

Arguments

Value

A ggplot object.

Examples

## Not run: 
l2g <- locus2GeneQuery(studyLocusId = "fa375739ca2a6b825ce5cc69d117e84b")
plot_l2g(l2g)

## End(Not run)

Description

This function queries the Open Targets GraphQL API to retrieve QTL credible sets data for a specified variant.

Usage

qtlCredibleSetsQuery(variantId, size = 500, index = 0)

Arguments

Value

Returns a tibble containing QTL credible sets data for the specified variant.

Examples

## Not run: 
result <- qtlCredibleSetsQuery(variantId = "19_10352442_G_C", size = 500, 
index = 0)

## End(Not run)

Description

This function queries the Open Targets GraphQL API to retrieve safety liabilities data for a specified gene.

Usage

safetyQuery(ensgId)

Arguments

Value

Returns a tibble containing safety liabilities data for the specified gene.

Examples

## Not run: 
result <- safetyQuery(ensgId = "ENSG00000141510")

## End(Not run)

Description

This function queries the Open Targets GraphQL API to retrieve shared trait studies data for specified disease IDs.

Usage

sharedTraitStudiesQuery(diseaseIds, size = 500, index = 0)

Arguments

Value

Returns a tibble containing shared trait studies data for the specified diseases.

Examples

## Not run: 
result <- sharedTraitStudiesQuery(diseaseIds = c("EFO_0004587"), size = 500, 
index = 0)

## End(Not run)

Description

targetLiability() is a convenience wrapper that combines the evidence returned by geneticConstraintQuery, safetyQuery and (optionally) depMapQuery into a single, interpretable liability score with a written rationale. It is intended as a quick triage step when prioritising drug targets: genes that are highly constrained, essential in cell lines, or already associated with safety events are flagged as risky for full inhibition, while genes lacking these signals may tolerate a partial or tissue-restricted approach.

Usage

targetLiability(ensgId, include_essentiality = TRUE, verbose = TRUE)

Arguments

Details

The overall liability_score is a weighted average (range 0-1, higher means greater liability) of up to three normalised components: genetic constraint (weight 0.40), known safety liabilities (0.35) and DepMap essentiality (0.25). Components without data are dropped and the remaining weights are renormalised. See Details for the mapping of each component.

Genetic constraint uses the loss-of-function (LoF) decile bin from geneticConstraintQuery() (gnomAD LOEUF, where bin 0 is the most constrained and bin 9 the least). The most constrained bin scores 1 and the least constrained scores 0.

Safety liabilities count the distinct events reported by safetyQuery(); the component saturates at five or more events.

Essentiality uses the median CRISPR gene-effect score across DepMap screens; a score of 0 (non-essential) maps to 0 and -1 (strongly essential) maps to 1.

This is a heuristic aid, not a validated clinical safety measure; always review the underlying evidence before acting on the score.

Value

A one-row tibble with the input identifiers, the individual component scores and flags, the combined liability_score, a liability_category ("Low", "Moderate" or "High"), a recommendation, and a human-readable rationale. Returns NULL if none of the underlying queries return data.

Examples

## Not run: 
# Score TP53 for inhibition liability
targetLiability(ensgId = "ENSG00000141510")

# Skip the DepMap essentiality call
targetLiability(ensgId = "ENSG00000169174", include_essentiality = FALSE)

## End(Not run)

Description

This function queries the Open Targets GraphQL API to retrieve UniProt literature evidence data for a specified gene and disease.

Usage

uniprotLiteratureQuery(ensemblId, efoId, size = 3500)

Arguments

Value

Returns a tibble containing UniProt literature evidence data for the specified gene and disease.

Examples

## Not run: 
result <- uniprotLiteratureQuery(ensemblId = "ENSG00000130203", efoId = 
"MONDO_0004975", size = 3500)

## End(Not run)

Description

This function queries the Open Targets GraphQL API to retrieve UniProt variants data for a specified variant.

Usage

uniProtVariantsQuery(variantId)

Arguments

Value

Returns a tibble containing UniProt variants data for the specified variant.

Examples

## Not run: 
result <- uniProtVariantsQuery(variantId = "4_1804392_G_A")

## End(Not run)

Description

This function queries the Open Targets GraphQL API to retrieve variant effect predictor data for a specified variant.

Usage

variantEffectPredictorQuery(variantId)

Arguments

Value

Returns a tibble containing variant effect predictor data for the specified variant.

Examples

## Not run: 
result <- variantEffectPredictorQuery(variantId = "4_1804392_G_A")

## End(Not run)

Description

This function queries the Open Targets GraphQL API to retrieve variant effect data for a specified variant.

Usage

variantEffectQuery(variantId)

Arguments

Value

Returns a tibble containing variant effect data for the specified variant.

Examples

## Not run: 
result <- variantEffectQuery(variantId = "4_1804392_G_A")

## End(Not run)

Description

This function queries the Open Targets GraphQL API to retrieve variants data for a specified study locus.

Usage

variantsQuery(studyLocusId, size = 500, index = 0)

Arguments

Value

Returns a tibble containing variants data for the specified study locus.

Examples

## Not run: 
result <- variantsQuery(studyLocusId = "fa375739ca2a6b825ce5cc69d117e84b", 
size = 500, index = 0)

## End(Not run)