Which pipelines do I need?

FunGen-xQTL computational protocol

Molecular QTL analysis from raw genotypes and phenotypes through discovery, meta-analysis, fine-mapping and GWAS integration.

Tell us about your data and goal

Molecular phenotypeAnyBulk RNA-seqsnRNA-seq / pseudobulkSplicingMethylationAPANone — summary statistics only

Analysis goalAnyDiscover xQTLsFine-map + TWAS weightsMulti-context sharingMeta-analyse cohorts 🚧Integrate with GWASRare-variant xQTL 🚧Enrichment / heritabilityScore variant impact

Fine-map fromAnyIndividual-level dataSummary statistics (needs LD reference)

Link to the trait byAnyNot doing GWAS integrationColocalisation, one phenotype vs one traitColocalisation across many phenotypes / contextsGene-level association (TWAS / cTWAS)Combine coloc and TWAS (INTACT)

Enrichment questionAnyNot running enrichmentDo my variants sit in this annotation?Enriched in regulatory features?Which pathways do my genes belong to?Heritability share (needs LD reference)

Genotype dataAnyRaw VCFPLINK, not yet QC'dPLINK, already QC'd and pruned

RelatednessAnyUnrelatedRelated individuals present

CohortsAnySingleMultiple

Contexts / cell typesAnySingleMultiple

Quantile / interaction QTLAnyNoYes

Try the example Reset

Inputs

Reference Data

• Ref. Preparation
• Generalized TADB
• LD Reference Pruning
• RSS LD Sketching
• LD Reference Generation

Quantification

Molecular Phenotype Quantification

Bulk RNA-seq

• Quantifying Expression
• Sample-level QC
• Counts Normalization

Single-nuclei / pseudobulk

• snRNA-seq Preprocessing
• Pseudobulk Preprocessing

Alternative splicing

• Splicing Calling
• Splicing Normalization

DNA methylation

• Methylation Calling

Polyadenylation

• APA Calling
• APA Imputation & QC

Pre-processing

Data Pre-processing

Genotype

• VCF QC
• Genotype Formatting
• GWAS QC
• PCA
• GRM

Phenotype

• Gene Annotation
• Phenotype Imputation
• Phenotype Formatting

Covariate

• Covariate Formatting
• Hidden Factors

Discovery

QTL Association Testing

• TensorQTL
• Quantile Regression QTL
• Post-processing

Multivariate modelling

Cross-cohort Meta-analysis

• METAL🚧

Multivariate Mixture (MASH)

• MASH Preprocessing
• Mixture Prior
• MASH Fitting
• MASH Posterior

Regression

High-dimensional Regression

Individual level

• Univariate fine-mapping
• Multivariate fine-mapping
• Univariate TWAS weights
• Multivariate TWAS weights

Summary statistics level

• Univariate SuSiE-RSS
• Univariate TWAS weights 🚧

Integration

GWAS Integration

• SuSiE-enloc
• TWAS & cTWAS
• ColocBoost
• INTACT

Rare-variant xQTL

• Watershed🚧

Interpretation

Enrichment & Validation

• Excess of Overlap (EOO)
• GSEA
• GREGOR
• S-LDSC

xQTL Modifier Score

• scEEMS Training
• scEEMS Prediction 🚧