Trans-PCO: to detect trans-eQTLs of cellular pathways and gene networks

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Updates

Our paper has been online! See bioarxiv preprint and the site with downloadable results.

Introduction

We developed the trans-PCO pipeline to detect trans-eQTLs that are associated with the expression levels of a group of genes (gene module) by using a PC-based multivariate association test [@liu2019geometric] that combines multiple gene expression PCs.

Trans-PCO allows the use of many types of gene groups or sets. For example, genes with correlated expression levels in a co-expression gene network, or genes in the same pathway, or protein-protein interaction network.

Figure: Three main steps in trans-PCO pipeline. The first step of trans-PCO pre-processes RNA-seq data to reduce false positive trans-eQTL associations due to read alignment errors. The second step involves grouping genes into gene sets, such as co-expression modules or biological pathways. The last step tests for trans-eQTLs of each gene set by a PC-based multivariate association test.

Main analysis

Simulations to evaluate the power of Trans-PCO

• Null simulations to show trans-PCO is well-calibrated

• Power simulation to compare trans-PCO to two other commonly used methods.

Calculate p-values of SNPs across the genome for each gene module by trans-PCO

• Analyze a RNA-seq dataset by trans-PCO pipeline

• Look at the distribution of identified trans-eQTLs

• Look at cis genes of trans signals

Colocalization analysis of trans signals and complex traits

• Perform colocalization analysis

• Colocalization proportion of trans-eQTLs with GWAS loci

S-LDSC to eveluate the enrichment of trait heritability in gene modules

• Perform S-LDSC between gene modules and complex traits

• Visualize the heritability enrichment of traits in gene modules

Colocalization analysis of trans signals and cis genes

• Perform colocalization analysis of trans signals and cis genes

• Visualization

Weekly updates

I also host a website to keep track of my weekly work in progress (a wflowr project).