Profiling Urine Methylation in Lupus Nephritis

Identifying urine DNA methylation signatures as a non-invasive biomarker for lupus nephritis class and disease progression.
Ongoing Systemic Diseases Systemic Lupus Erythematosus (SLE) Bioinformatics Biomarker Discovery Data-Driven & Quantitative Disease Subtyping Experimental Platforms & Models Human Cohorts Multi-omics Integration Single Cell Technologies Translational & Clinical

Funding Year: 2024

Project Overview

Diagnosing lupus nephritis currently requires a kidney biopsy — an invasive procedure with significant limitations. This project explores a non-invasive alternative by identifying DNA methylation signatures in urine that correlate with lupus nephritis class. DNA methylation is a stable, cost-effective, and reproducible marker that influences gene expression and reflects disease state. The research pursues two goals: establishing a link between urine cell-free DNA methylation patterns and lupus nephritis class using ddPCR, and characterizing the cellular landscape of lupus nephritis using single-nucleus RNA sequencing from FFPE tissue, correlated with bulk methylation sequencing from urine pellets.

Impact & Innovation

A urine test for lupus nephritis diagnosis

 

By identifying DNA methylation signatures in urine that correlate with lupus nephritis class, this project offers a stable, cost-effective, and reproducible alternative to kidney biopsy — with broad applicability across kidney disease contexts.

  • Establishes urine DNA methylation as a novel, non-invasive biomarker for lupus nephritis classification, applicable to IgA nephropathy, ANCA-associated disease, and beyond
  • Generates IP potential through a ddPCR-based diagnostic workflow and Matchmaker, a novel computational method for matching single-cell RNA to single-nucleus methylation data
  • Advances the Consortium’s From Mechanistic Insight to Translation pillar by bridging epigenetic discovery to a clinically deployable, non-invasive diagnostic tool
Research Approach

A framework designed for discovery

This project combines cell-free DNA methylation profiling with single-nucleus RNA sequencing and a novel computational matching method to establish non-invasive biomarkers for lupus nephritis class and characterize its cellular landscape. The work integrates molecular and epigenetic approaches to move from discovery to diagnostic application.

ddPCR-based analysis of DNA methylation patterns in urine cell-free DNA, single-nucleus RNA sequencing from FFPE kidney tissue, bulk methylation sequencing from urine pellets, and application of Matchmaker — a novel computational method for matching single-cell RNA sequencing clusters to single-nucleus methylation data.

Urine cell-free DNA and pellet samples from individuals with lupus nephritis, FFPE kidney tissue for single-nucleus RNA sequencing, and paired methylation and transcriptomic datasets used to build and validate the epigenetic atlas of lupus nephritis.

Identification of urine DNA methylation signatures that distinguish lupus nephritis classes and correlate with disease progression, with the goal of developing a cost-effective, non-invasive diagnostic tool applicable across kidney disease contexts and scalable for clinical use.

Investigators & Institutions

Powering the science

Principal Investigator

Christine Bakhoum, MD, MAS, Colton Consortium Member

Assistant Professor, Department of Pediatrics (Pediatric Nephrology), Yale School of Medicine, Yale University

Colton Centers & Institutions

Colton Center for Autoimmunity at Yale University

Research Outputs

From insight to impact

Publications

Associations between blood DNA methylation and histopathologic features in lupus nephritis

Kidney360
Demkowicz, PC; Kavaliauskaitė, I; Faulkner, SC; Kent, C; Shaw, M; Kumar, D; Ix, JH; Wilson, FP; Moledina, DG; Bakhoum, MF; Bakhoum, CY August 2025
BioinformaticsBiological & MechanisticBiomarker DiscoveryData-Driven & QuantitativeDisease SubtypingExperimental Platforms & ModelsHuman CohortsHuman GeneticsMulti-omics IntegrationTranslational & ClinicalSystemic DiseasesSystemic Lupus Erythematosus (SLE)Yale University