Opeoluwa-Shodipe/Malariares2025

After the publication "Eradicating Malaria in Africa: Potentials and Challenges of Vaccine Deployment" I was inspired to see eradication from another point of view (POV) by applying my bioinfomatics skillset, I need to see firsthand what is happening in the genome, and what is causing resistance? # Replication of Single-cell Transcriptomics Revealing Inter-ethnic Variation in Immune Response to *Plasmodium falciparum* This repository contains a **full replication analysis** of the study: > **Shahin et al. (2025)** > *Single-cell transcriptomics reveals inter-ethnic variation in immune response to Falciparum malaria* > **The American Journal of Human Genetics**, 112, 709–723 Using publicly available single-cell RNA sequencing data, this project reproduces and visualizes key findings demonstrating how **ethnicity-driven immune programming**, rather than infection status alone, shapes malaria outcomes. --- ## 🎯 Scientific Motivation Why do Fulani children in West Africa experience **less severe malaria** than neighboring Mossi children despite comparable exposure to *P. falciparum*? This analysis addresses that question by exploring **baseline and infection-induced immune states** across more than **70,000 single immune cells**, revealing how population-level genetic and transcriptional differences shape disease tolerance. --- ## 🧠 Key Biological Insights (Replication Summary) ### 1️⃣ Ethnicity Dominates Immune Variation Across multiple immune cell types, **ethnicity explains 10–40× more transcriptional variation** than infection status itself. **Implication:** Disease severity may be predicted by **pre-infection immune states**, not just pathogen burden. --- ### 2️⃣ Trained Tolerance in Fulani Monocytes Fulani monocytes exhibit: - ↓ Pro-inflammatory cytokines (TNF-α, IL-6, NF-κB) - ↑ Phagocytic and parasite-clearance receptors (e.g. CD36) **Interpretation:** Parasites are cleared efficiently **without triggering harmful inflammation**, reducing risk of severe malaria. --- ### 3️⃣ Compartmentalized Immune Strategy Different immune compartments play distinct roles: | Cell type | Dominant function | |---------|------------------| | Monocytes | Silent parasite clearance | | B cells | Robust antibody activation | | CD4⁺ T cells | Dampened activatio …