Task Force: V2F

— Variant to Function (V2F)

V2F TF Priorities

To establish a coordinated international infrastructure for in vitro experimentation, high-throughput regulatory variant testing, and genome editing across livestock species, providing the functional data needed to close the loop between computational predictions and biological phenotypes. The FAANG V2F (Variant-to-Function) Task Force focuses on the precise manipulation of cellular environments to enable targeted perturbation experiments for variant-to-function validation in livestock species. The Task Force aims to: Precisely manipulate cellular environments and design targeted perturbations for variant-to-function validation; Validate and refine hypotheses generated by in silico and in vivo approaches; Explore and generate new working hypotheses using genome-wide functional screens (e.g. MPRA, CRISPR).

By providing robust experimental frameworks, the Task Force will enable systematic interpretation of regulatory and coding variants and their effects on molecular and biological phenotypes.

1. Establish shared in vitro functional genomics infrastructure
Develop and coordinate reference resources for in vitro experimentation in farmed animals, including:
• Cell lines
• Primary cell cultures
• Organoids and advanced cellular systems
These resources will provide standardized experimental platforms for variant-to-function validation across species.
2. Standardise experimental and perturbation protocols
Promote reproducible and interoperable experimental workflows by developing and sharing standard protocols for:
• Genome editing (e.g. CRISPR-based perturbations)
• In vitro perturbation models
• MPRA and other high-throughput reporter assays
3. Enable high-throughput regulatory variant testing
Support genome-wide functional screening approaches to:
• Validate computationally predicted regulatory variants
• Identify causal variants underlying complex traits
• Generate new working hypotheses for downstream in vivo validation
4. Integrate multi-modal functional data
Facilitate the integration of diverse experimental data types, including:
• Epigenomics
• Imaging
• Cell-state profiling
• Multi-omics
This will allow systematic interpretation of variant effects across molecular layers
5. Close the loop between prediction and phenotype
Provide the functional data needed to:
• Validate and refine in silico predictions
• Support variant prioritisation for breeding and genome editing
• Enable reproducible variant-to-phenotype pipelines in livestock
6. Promote interoperability across FAANG Task Forces
Ensure close alignment with:
• FAANG Predictions
• FAANG Comparative Genomics
• FAANG Single Cell
• Farm GTEx
• MetaFAIR and Metadata workflows
to support an integrated FAANG functional genomics ecosystem.
7. Build community capacity and training
Create opportunities for:
• Training and skills development
• Early-career researcher mobility
• Cross-disciplinary exchange

General planned activities

• Networking with established and new users and developers of in vitro research techniques in farmed animals
• Outreach to other FAANG communities
• Joint seminar series with other FAANG Task Forces (shared calendar)
• Identification and coordination of target measures, including:
• Sharing of reference samples
• Development of standard protocols