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STAT Hyperactivation in Pediatric Sepsis

JCI Article GEO

This repository contains analysis code associated with the following manuscript:

Aberrant STAT signaling and T cell dysregulation define a targetable pediatric sepsis endotype Robert B. Lindell et al. Journal of Clinical Investigation. 2026;136(14):e202867. https://doi.org/10.1172/JCI202867


Overview

Sepsis and multiple organ dysfunction syndrome (MODS) in children are characterized by substantial immune heterogeneity, limiting the development of targeted immunomodulatory therapies. In this study, we integrated plasma proteomics, immune phenotyping, single-cell transcriptomics, T cell receptor repertoire analysis, and phosphoflow cytometry to define immune endotypes in critically ill children with MODS.

The study identifies a high-severity pediatric sepsis/MODS endotype characterized by IL-6/IFN-γ-associated inflammation, STAT1/STAT3 signaling dysregulation, T cell activation, impaired T cell transcriptional programs, and altered CD8+ T cell responses.

This repository is intended to provide analysis code and documentation supporting transparency and reproducibility of selected analyses from the published manuscript.


Repository Contents

.
├── README.md
└── R Codes/
    ├── ProcessData.R
    ├── Plot_Figure6.R
    ├── TCR_screpertoire_code.R
    └── cellchat.R

Script Descriptions

Script Description
R Codes/ProcessData.R Data processing and formatting steps used for downstream analyses. This script includes preprocessing operations applied to study-derived datasets before figure generation and analytic workflows.
R Codes/Plot_Figure6.R Code used for analyses and visualization related to Figure 6 of the manuscript.
R Codes/TCR_screpertoire_code.R Code used for T cell receptor repertoire analysis, including workflows based on the scRepertoire R package.
R Codes/cellchat.R Code used for cell-cell communication analysis, including workflows based on the CellChat R package.

Data Availability

Resource Location
Transcriptional data GEO accession GSE303333
Figure source values Published article’s Supporting Data Values file
Analysis code This GitHub repository

Important

This repository contains analysis code and associated materials intended to support transparency and reproducibility of the published analyses. It does not contain protected health information. Raw or potentially identifiable human subject-level clinical data are not included in this repository.


Reproducibility Notes

The scripts in this repository document selected analytic workflows used in the manuscript. Some analyses require input files generated from study-specific preprocessing pipelines or data files available through the journal supplement, GEO accession, or controlled study records.

Package versions, input data formatting, and computational environments may affect exact reproduction of figures and summary statistics. Required R packages are loaded within the individual scripts.

Note

Users who wish to reproduce specific analyses should review the corresponding script, ensure that required input files are available in the expected format, and update local file paths as needed.


Citation

Please cite the published manuscript if using this code:

Lindell RB, et al. Aberrant STAT signaling and T cell dysregulation define a targetable pediatric sepsis endotype. Journal of Clinical Investigation. 2026;136(14):e202867. https://doi.org/10.1172/JCI202867


Contact

For questions about the code or analyses, please contact:

Robert B. Lindell, MD
Children’s Hospital of Philadelphia
University of Pennsylvania
Website: Lindell Lab
Email: LindellR@chop.edu
GitHub: https://github.com/Lindell-Lab

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