README for TEDDY Microbiome-Genetics Analysis

This repository contains the code for the manuscript "Gut Microbiome Maturation in Early Childhood Interacts with Host Genetics to Predict Type 1 Diabetes Risk." The code covers analyses of microbiome maturation pattern clustering, comparisons of IA/T1D risk across clusters, and linear mixed models for genetic–microbiome associations over time in the TEDDY study.

1. Dependencies

R (version 4.2.3) with the following packages:

• tidyverse (v2.0.0)
• lmerTest (v3.1.2)
• traj (v2.0.1)
• survival (v3.5-5)
• doParallel (v1.0.17)
• foreach (v1.5.2)

To install all required packages, run:

install.packages(c("tidyverse", "lmerTest", "traj", "survival", "doParallel", "foreach"))

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2. Scripts

Analysis Scripts:

• Analysis scripts are stored in the analysis_script/ folder:
  • run_trajactory.R: Performs clustering of microbiome maturational patterns and compares the relative risk of IA/T1D across different clusters.
  • run_LMM.R: Implements linear mixed models with random effects to study genetic and microbiome associations over time.

Figures Scripts: The Figure_scripts/ folder contains all scripts used to generate the figures in the manuscript.

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3. Demo

Demo data are included in the demo/ folder, containing:

• microbiome_demo.tsv: Example microbiome data.
• genetics_demo.tsv: Example genetic data.
• metadata_demo.tsv: Example metadata.

To run the trajectory analysis and generate results:

Rscript run_trajactory.R -i ./demo/microbiome_demo.tsv \
                        -g ./demo/genetics_demo.tsv \
                        -m ./demo/metadata_demo.tsv \
                        -o ./demo/output

To run linear mixed models to study genetic and microbiome associations over time:

Rscript run_LMM.R -m ./demo/metadata_demo.tsv \
                    -g ./demo/genetics_demo.tsv

Expected Outputs:

• output/cluster_results.tsv.pdf: Trajectory clustering results.
• output/relative_risk.tsv: Relative risk results of trajectory patterns.
• output/model_anova_total.tsv: Results for genetic and microbiome associations over time.

Expected run time for the demo on a standard desktop computer is approximately less than 1 minutes.

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