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tooluniverse-gene-liability

Scores human safety liability of gene knockout, knockdown, or pharmacological inhibition using multi-source evidence.

1.7k|254|Updated Mar 3, 2025
Search Tags:#drug discovery#essentiality#genetic constraint#target safety#on-target toxicity#gene liability#knockout phenotype
One-click install
npx skills add https://github.com/mims-harvard/ToolUniverse --skill tooluniverse-gene-liability
Or copy as Structured Prompt for Agent▼
Please help me install this Agent Skill.
Skill: tooluniverse-gene-liability
Source: https://github.com/mims-harvard/ToolUniverse/tree/main/plugins/tooluniverse/skills/tooluniverse-gene-liability
Command: npx skills add https://github.com/mims-harvard/ToolUniverse --skill tooluniverse-gene-liability

SYSTEM DOCUMENTATION & REQUIREMENTS

What problem does it solve?

Deciding whether reducing a gene's function is safe requires synthesizing scattered evidence from genetics databases, knockout models, expression atlases, and drug safety records. This Skill automates that synthesis into a transparent 0-100 liability score with a recommended modulation strategy.

Core Features & Use Cases

  • Five-dimension scoring: Weighs human genetic constraint (gnomAD), mammalian knockout phenotype (OpenTargets/MGI), critical-organ expression (GTEx/HPA), observed on-target effects, and cellular essentiality (DepMap) into a single liability score.
  • Evidence-tiered confidence: Grades every observation T1-T4, reports evidence coverage, and refuses to publish a categorical score below 60% coverage.
  • Actionable recommendations: Translates the score into guidance on partial versus complete inhibition, transient versus irreversible modulation, tissue-targeted delivery, or deprioritization.
  • Use Case: A drug discovery team evaluating whether to advance a kinase inhibitor target can submit the gene symbol and modality to receive a scored liability verdict with citations, red flags, and the key experiments needed to close evidence gaps.

Quick Start

Evaluate the safety liability of knocking out gene PCSK9 with a reversible inhibitor modality and recommend a modulation strategy.

Frequently Asked Questions about tooluniverse-gene-liability

High-intent search queries and answers about installing and using this skill.

FAQPage Schema
How do I assess whether a gene is safe to knock out or inhibit?▼

Submit the gene symbol, Ensembl ID, or UniProt accession along with the intervention modality. The skill gathers human genetic constraint, knockout phenotype, expression, on-target, and essentiality evidence, then returns a 0-100 liability score with a modulation recommendation.

What databases are used for gene target safety assessment?▼

The workflow queries gnomAD for loss-of-function constraint, OpenTargets for mouse knockout phenotypes and target safety profiles, GTEx and HPA for tissue expression, ClinVar for variants, and DepMap for cancer-cell dependency data.

Does DepMap essentiality mean a gene is essential in normal tissue?▼

No. DepMap measures cancer-cell essentiality only and must not be interpreted as normal-tissue essentiality. The skill treats it as one 10-point dimension and marks it unavailable if only gene metadata without dependency scores is returned.

What happens when safety evidence for a gene is incomplete?▼

Missing dimensions are excluded from the denominator rather than scored as zero. If evidence coverage falls below 60%, the skill reports insufficient evidence and lists the specific experiments or datasets needed instead of publishing a score.

Can a gene liability score replace a clinical safety determination?▼

No. The output is a research risk assessment, not a clinical safety determination. It summarizes published evidence and recommends modulation strategies, but regulatory or clinical decisions require dedicated preclinical and clinical studies.

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