PANoptosis-Based Diagnostic Model Using Single-Cell and Transcriptome RNA Sequencing to Predict Rejection in Kidney

Qian Chen1, Sheng Chao, Chao Liu

  • 1From the Department of Organ Transplantation, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, China.

Abstract

Insights

Researchers identified seven core PANoptosis genes linked to kidney transplant rejection using single-cell and machine learning analysis. A predictive model showed promise, and tosyllysyl chloromethane was identified as a potential therapeutic agent for rejection.

Area of Science:

  • Immunology
  • Genomics
  • Transplantation Medicine

Background:

  • Kidney transplantation is the optimal treatment for end-stage renal failure.
  • Transplant rejection remains a significant clinical challenge.
  • The specific role of PANoptosis in kidney transplant rejection is not well-defined.

Purpose of the Study:

  • To investigate the role of PANoptosis-related genes in kidney transplant rejection.
  • To identify key PANoptosis genes associated with transplant rejection.
  • To develop a predictive model and identify potential therapeutic targets for rejection.

Main Methods:

  • Single-cell RNA sequencing analysis of PANoptosis-related genes in kidney transplant rejection.
  • Application of machine learning algorithms to identify core PANoptosis genes.
  • Construction and validation of a clinical predictive model.
  • Drug repurposing analysis using the DSigDB database.

Main Results:

  • Rejection samples exhibited altered cell proportions, including increased endothelial cells and macrophages.
  • Seven core PANoptosis genes were identified and found to be significantly correlated with rejection.
  • The developed predictive model demonstrated high accuracy and good calibration.
  • Tosyllysyl chloromethane was predicted as a potential therapeutic agent targeting NFKBIA.

Conclusions:

  • A proof-of-concept diagnostic model for kidney transplant rejection based on seven core PANoptosis genes was developed.
  • Clinical validation of these genes is necessary for diagnostic and prognostic applications.
  • Tosyllysyl chloromethane targeting NFKBIA presents a promising therapeutic strategy for renal transplant rejection.