Platform

How Aqtual measures active disease biology from a blood draw

Aqtual analyzes active-chromatin cfDNA from a single blood draw to measure biological activity associated with different tissues and cellular programs. Explore how the assay works, the evidence behind the approach, and where it can be applied.

Capturing active gene expression in cell-free DNA

Most liquid biopsy assays profile short nucleosomal cfDNA fragments, which primarily reflect the global chromatin state. Emerging active chromatin cfDNA methods rely on antibody-based chromatin immunoprecipitation, limiting their scope and scalability. Aqtual's platform instead selectively captures longer cfDNA fragments associated with active gene expression. These regulatory-chromatin fragments preserve epigenetic and transcription-coupled signatures, providing a direct, RNA- and antibody-free readout of a cell's gene expression activity.

FRAGMENT SIZE DISTRIBUTIONRecovered cfDNA fragmentsConventional cfDNA100200300400500600700800FRAGMENT SIZE (BP)~167 BPAqtual active-chromatin cfDNA100200300400500600700800FRAGMENT SIZE (BP)~370 BPSHORT-FRAGMENT BIASMisses regulatory signalLONGER-FRAGMENT RECOVERYEnables regulatory insightsCONVENTIONAL cfDNA······ENHANCERPROMOTERGENE BODYAQTUAL ACTIVE-CHROMATIN cfDNAEnhancer signalRegulatory elementsrevealedPromoter signalClear initiationactivityGene-body readoutTranscribed regionscaptured

Functional disease biology resolved as tissue states.

Genomic features from active chromatin cfDNA are mapped to known blood- and tissue-specific pathways to determine the signal's origin. Regulatory programs and actively transcribed genes underpin the functional state of the originating cell or tissue. The resulting data readout is a structured, universal, pathway-based ontology that can be compared across cohorts, time points, and treatments.

  1. PatientRoutine blood draw
  2. PlasmaActive-chromatin cfDNA
  3. SignalResolved by tissue
Patient tissue state
Inflam.IFNTNF/NF-kBJAK-STATProlif.FibrosisRepairSynoviumSkinGut epitheliumMyeloidT cellsB cellsLiverKidneyEndothelium

Each box is one tissue or cell type running one biological program; intensity shows deviation from a healthy baseline.

BaselineShifted

Changes in tissue states indicate disease trajectory.

Our active-chromatin profiling connects liquid and tissue biopsies, enabling a practical, non-invasive clinical method to assess tissue-specific biology at multiple time points. This approach supports longitudinal studies, offering new insights into patient treatment and disease progression that were previously inaccessible without invasive tissue biopsies.

Assessing how tissue states shift their trajectories provides mechanistic context for addressing key translational questions:

  • How do biological programs active at baseline change as disease burden increases?
  • How do individual baseline programs respond to different treatment modalities?
  • What resistance versus protective mechanisms evolve with treatment, leading to disease progression or remission?

Linking assay results to clinical outcomes clarifies how tissue states change directionality across the disease course.

DEVIATION FROM HEALTHY →UNTREATEDRESPONDERREMISSIONNON-RESPONDERRESISTANCE / PROGRESSIONBASELINEDISEASE PROGRESSIONDISEASE COURSE →

Structured disease ontology for addressing translational and clinical research questions

Active-chromatin functional liquid biopsy reveals the tissue-specific biological processes underpinning disease and response to therapy. By comparing cohorts and tracking changes in individual patients, we are advancing disease detection, combination therapy, and patient stratification and monitoring in fields such as rheumatoid arthritis, autoimmune diseases, and oncology.

Prevention

Can early intervention rescue trajectories trending toward disease?

PRE-DISEASE
Diagnosis

What tissue state reflects the transition from healthy to disease?

ONSET
Therapy selection

What drug mechanism of action best resolves the patient's disease tissue state?

DECISION
Monitoring

Does the altered trajectory align with expectations?

ON THERAPY
Drug development

What quantitative biomarkers inform therapy-dependent changes in trajectory?

TRIALS
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