Shared and disease-specific pathways in frontotemporal dementia, Alzheimer’s and Parkinson’s diseases

Table of contents

• Introduction
• Content
• Data
• License
• Instructions

Introduction

This repository contains the code for bioinformatics analyses described in the article "Shared and disease-specific pathways in frontotemporal dementia, Alzheimer’s and Parkinson’s diseases".

This project investigated plasma proteomics data from the SomaScan 7K platform in over 10K individuals from the Global Neurodegeneration Proteomics Consortium (GNPC). This data is utilized to identify proteins associated with Alzheimer disease (AD), Parkinson disease (PD), and Frontotemporal dementia (FTD). Idnetified proteins were leveraged to create disease-spcific prediction models, uncover shared and distinct proteomic alterations across these diseases. We also performed biological pathways and cell type enrichment analyses to understand underlying disease biology.

Content

The code covers the following main analysis steps:

1. Data pre-processing: Proteomics data preparation, QC, and normalization
2. Differential expression analyses
3. Disease correlation analyses
4. Pathway enrichment analyses
5. Cell type enrichment analysis
6. Network and perturbation analyses
7. Prediction model development using Lasso regression
8. Sensitivity analyses

Data

Pre-processed and normalized proteomic datasets used in preparing this manuscript will be shared at the Global Neurodegeneration Proteomics Consortium (https://www.neuroproteome.org/) website in July 2025.

License

The code is available under the MIT License.

Instructions

The code was tested on R 4.3.0 on Linux operating systems, but should be compatible with later versions of R installed on current Linux, Mac, or Windows systems.

To run the code, the correct working directory containing the input data must be specified at the beginning of the R-scripts, otherwise the scripts can be run as-is.