Olink Liver Proteomics Explorer: UK Biobank Analysis

🌐 Live Application

Access the interactive app here: https://tme34.shinyapps.io/proteomics/

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📋 Overview

This R Shiny application is an interactive exploratory platform designed to analyze the intersection of ~3,000 Olink protein measurements and liver-related clinical endpoints within the UK Biobank (UKBB).

The application allows researchers to move beyond simple observational associations by incorporating genetic variants and multiscale transcriptomic filters. This enables a triangulation approach to identify proteins that are biologically localized to the liver and potentially causal in disease progression.

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🧪 Key Features

🧫 Multiscale Biological Filtering

To ensure biological relevance, the app allows users to filter proteins based on their expression profiles across different scales:

• GTEx Bulk RNA-seq Integration: Filter for Liver-Specific proteins. This ensures that the proteins being analyzed are predominantly expressed in liver tissue, reducing systemic noise.
• Single-Cell RNA-seq Mapping: Filter proteins by their highest-expressing cell type (e.g., Hepatocytes, Stellate Cells, Kupffer Cells). This helps pinpoint which specific cell niche is driving the proteomic signal observed in the blood.

🧬 Genetic Triangulation

The app integrates genotype data for key genetic instruments for liver fat:

• PNPLA3 (rs738409), TM6SF2 (rs58542926), and HSD17B13 (rs72613567).
• $\beta$-$\beta$ Plot Mode: Compare observational protein-trait effects against genetic-protein effects to assess causality.

📊 Exploratory Analytics

• Volcano Plots: Rapidly visualize high-impact proteins for endpoints like PDFF, HCC, and Cirrhosis.
• Interactive Tables: Search and filter pre-computed regression statistics for all 3,000 proteins.

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📂 File Structure

The project is organized into a root directory containing the documentation and a dedicated /app folder containing the Shiny environment and databases:

├── README.md                   # Project documentation
└── app/                        # Main application directory
    ├── ui.R                    # User Interface script
    ├── server.R                # Server logic and data processing
    ├── proteomics_mri_ct1_dataset.csv     # Main UKBB regression results
    ├── proteomics_mri_ct1_dataset_inv.csv # Inverse-normalized datasets
    ├── average_protein_measurements_by_cell_type.csv # Cell-type expression data
    ├── scRNA_enriched.csv       # Single-cell enrichment/specificity metrics
    ├── .Rhistory                # R session history (Local use only)
    └── rsconnect/               # Deployment metadata for shinyapps.io