Network-based Analysis of Trans-eQTLs in Schizophrenia

This repository contains code, data structures, and documentation supporting the MSc Bioinformatics thesis project “Network-based Analysis of Trans-eQTLs in Schizophrenia”.
The project applies graph-theoretic and functional genomics approaches to investigate how noncoding genetic variants regulate gene expression across human brain regions.

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Overview

Schizophrenia (SCZ) is a highly polygenic psychiatric disorder where most risk variants map to noncoding regulatory regions. Many of these variants influence gene expression through expression quantitative trait loci (eQTLs).

While cis-eQTLs (local regulation) are well-characterised, trans-eQTLs (distal regulation) remain underexplored due to smaller effect sizes and statistical challenges. This project develops a systems-level framework to study trans-eQTLs by:

• Constructing bipartite SNP–gene networks from MODULE-predicted trans-eQTL weights.
• Applying stochastic block modelling (SBM) with the graph-tool library to infer modular structure.
• Computing node centrality (degree, PageRank, betweenness) to identify hub SNPs and genes.
• Visualising module–module interactions with Sankey diagrams.
• Performing GO enrichment analysis of high-centrality genes to uncover functional themes.
• Comparing SBM-derived modules with WGCNA co-expression modules using normalized mutual information (NMI).

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Computational Environment

Python (3.10.11, macOS M1 Pro)

• graph-tool – SBM inference and centrality metrics
• pandas, numpy – data handling
• matplotlib, seaborn, plotly – plots and Sankey diagrams
• scikit-learn – NMI computation
• pyreadr – import of .rds files

R (4.3.1, Windows 10)

• topGO, org.Hs.eg.db, AnnotationDbi – GO enrichment
• dplyr, readr, ggplot2 – data handling and plots
• tibble, purrr, stringr, janitor – supporting utilities

All analyses are reproducible through scripted pipelines with structured outputs.

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Citation

If you use this code or data, please cite:

Azaadeh, Y. (2025). Network-based Analysis of Trans-eQTLs in Schizophrenia (MSc Thesis, University of Birmingham).

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License

This project is licensed under the Creative Commons Attribution 4.0 International License (CC BY 4.0).
You are free to share and adapt the material with appropriate credit.

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Contact

Author: Yasmin Azaadeh
GitHub: @YasminAzaadeh

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