gpaasi/hbs-differentiation-uganda

Reproducible workflow to quantify HbS (HBB) differentiation across Ugandan subregions and test whether malaria burden and geography jointly align with locus-specific genetic structure. R pipeline, HWE/FIS, Weir–Cockerham FST, distance matrices (genetic, geographic, PfPR2–10), MMRR joint inference, PCoA/dbRDA, and Rousset IBD sensitivity analysis. # Malaria burden and geographic distance jointly predict HbS differentiation in Uganda ## Table of Contents - Overview - Repository structure - Data description - Installation and environment setup - Workflow 1: Data ingestion and subregion summaries - Workflow 2: Differentiation and distance matrices - Workflow 3: Primary joint inference (MMRR) - Workflow 4: Secondary analyses (PCoA and dbRDA) - Workflow 5: Sensitivity analyses (Mantel and Rousset) - Workflow 6: Figures, tables, and report rendering - Running the full pipeline - How to cite - License - Contact information --- ## Overview This repository contains code, configuration templates, and documentation to reproduce the analysis for: **Malaria burden and geographic distance jointly predict HbS differentiation in Uganda** We quantify locus-specific spatial structure at the sickle-cell variant (HbS) in **HBB** using haemoglobin genotype data aggregated to 15 Ugandan subregions. We then test whether pairwise differentiation aligns with malaria-burden dissimilarity (PfPR\(_{2–10}\)) after accounting for geographic separation. Objectives: - Summarize subregional genotype composition (HbAA, HbAS, HbSS) and HbS allele frequency. - Quantify locus-specific differentiation using global and pairwise Weir–Cockerham \(F_{ST}\). - Construct genetic, geographic, and malaria-burden dissimilarity matrices. - Estimate independent associations of geographic distance and PfPR dissimilarity with HbS differentiation using multiple matrix regression with randomization (MMRR) (primary inference). - Provide secondary multivariate summaries (PCoA, dbRDA) and sensitivity analyses (Mantel-family tests, Rousset IBD regression). - Produce manuscript-ready tables and figures. ## Repository structure ```text uganda-hbs-malaria-distance/ ├── README.md ├── CITATION.cff ├── LICENSE ├── .gitignore ├── .github/ │ └── workflows/ ├── code/ │ ├── config/ │ │ ├── config.yml │ │ └── paths.example.yml │ ├── pipeline/ │ …