Liquid Biopsy cfDNA Analysis | Tissue-of-Origin Profiling

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Circulating cell-free DNA (cfDNA) carries methylation signatures that reflect its tissue and cellular origin, enabling minimally invasive deconvolution of cellular injury, turnover, and disease activity from blood and other biofluids.
Renew provides integrated cfDNA sequencing and deconvolution bioinformatics services to identify the biological source of circulating DNA signals from plasma and other body fluids for research and translational applications.
Built on native nanopore sequencing and established deconvolution principles, this approach supports tissue-of-origin analysis across cell types, tissues, and disease areas where cfDNA source attribution is biologically or clinically meaningful.

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Cell-Type Informed Liquid Biopsy Analysis

Renew combines native whole-genome methylation atlas generation, classifier development, and cfDNA deconvolution to identify the tissue or cellular source of circulating DNA signals from blood and other body fluids.

This Approach Enables

Native whole-genome methylation reference atlas generation for specific cell types and tissues

Custom cell-of-origin classifier development for translational and disease-focused applications

Body fluid-based detection of tissue- and cell-type-informed cfDNA methylation signals

Which Supports

Direct methylation profiling without bisulfite conversion, PCR bias, or fixed array probe sets

Flexible expansion to additional cell populations, tissues, and biological questions over time

Minimally invasive monitoring of cell turnover, injury, and disease activity from plasma and other biofluids

Applications

Renew has applied this platform across internal and partner programs to bring cellular resolution to liquid biopsy, including NeuroLens for detecting elevated neuron-like cfDNA methylation signals associated with neurodegeneration in disorders such as Alzheimer's and Parkinson's disease, and NOA Guide for predicting fertility outcomes in men with non-obstructive azoospermia. Together, these applications demonstrate the platform's versatility in translating circulating DNA signals into biological insight across diverse disease areas.

Current blood biomarkers for neurodegenerative disease largely reflect aggregate pathology or downstream injury responses and provide limited insight into which brain regions or neuronal populations are actively affected. Cell-free DNA (cfDNA) offers a complementary signal because it retains methylation patterns linked to tissue and cellular origin, enabling cell-of-origin analysis from blood.

NeuroLens applies native nanopore methylation sequencing to generate a brain methylation atlas and deconvolute plasma cfDNA. For this proof-of-concept application, whole-genome methylation references were generated from primary human cortical, dopaminergic, and spinal motor neurons, along with astrocytes, microglia, and Schwann cells. Derived classifiers were applied to blood plasma samples from Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and healthy controls.

Nine NeuroLens ROC curves comparing sensitivity and false positive rate across AD, MCI, PD, ALS, and control groups.

Figure 1. Integrated primary neuron cfDNA methylation signatures improve disease-group discrimination across neurodegenerative conditions. NeuroLens classifiers based on primary cortical (A), dopaminergic (B), and spinal motor neuron-like (C) cfDNA methylation signatures were evaluated across Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and control cohorts. Individual primary neuron classifiers were compared with integrated multi-neuron models (D–F), which achieved strong discrimination for AD (AUC = 0.98), PD (AUC = 0.96), and ALS (AUC = 0.86) in multi-disease settings. Both individual and integrated primary neuron classifiers outperformed analogous iPSC-derived cortical, dopaminergic, and spinal motor neuron classifiers (AUCs = 0.51–0.64), supporting the value of primary human neuron methylation references and multi-neuron cfDNA methylation deconvolution for biologically informed liquid biopsy profiling of neurodegeneration.

Renew combines platform flexibility, nanopore expertise, and operational excellence to resolve areas of the genome that standard approaches cannot.

Methylation-Based Tissue-of-Origin Liquid Biopsy

Cell-Type Informed Liquid Biopsy Analysis

Applications