Score a target's safety liability for inhibition or knockout.

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

ensgId: Character: ENSEMBL ID of the target gene (e.g., "ENSG00000141510").
include_essentiality: Logical: whether to query DepMap essentiality as part of the score. Set to FALSE to skip the extra API call (default: TRUE).
verbose: Logical: print the rationale to the console (default: TRUE).

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.

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.

Examples

if (FALSE) { # \dontrun{
# Score TP53 for inhibition liability
targetLiability(ensgId = "ENSG00000141510")

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