Project Details
Description
Summary
Profiling small non-coding microRNAs (miRNAs) in biofluids is a practical and promising strategy for non-invasive diagnostics. MiRNAs are released into the blood in a mixture of soluble stabilizing carriers i.e. protein-complexes, lipoproteins, platelets and extracellular vesicles (EVs). EV-bound miRNAs are thought to be stably protected during sample collection, processing and storage. We discovered a panel of EV-miRNAs that predict disease activity in patients with Lymphoma before, during and after treatment. Nevertheless, key challenges remain before EV-miRNA signatures can be translated into clinical practice.
Key challenges
- Factors determining miRNA variability in plasma/urine are unknown
- Limitations in practical EV isolation/purification methods
- Demonstrating cancer-relatedness of EV-miRNAs in biofluids
- Inaccuracy EV-miRNA profiling techniques due to technical bias
HypothesisReducing technical and biological noise will unleash the promise of cell-freemiRNA as liquid biopsy strategy in clinical practice.
Objectives
1) Develop a practical, reproducible method for EV isolation and EV-miRNA extraction compatible with small RNAseq profiling and IVD-compliant qRT-PCR analysis
2) Demonstrate feasibility of a glycomics strategy to enrich for tumor-derived EV-miRNAs in plasma of patients with Lymphoma
3) Develop an unbiased EV-miRNAseq method, design and apply ‘calibrator spike-inns’ to guide quantitative bioinformatics data acquisition
4) Evaluate and develop machine learning and statistical classifier models for discovery and validation of EV-miRNA signatures/panels
Profiling small non-coding microRNAs (miRNAs) in biofluids is a practical and promising strategy for non-invasive diagnostics. MiRNAs are released into the blood in a mixture of soluble stabilizing carriers i.e. protein-complexes, lipoproteins, platelets and extracellular vesicles (EVs). EV-bound miRNAs are thought to be stably protected during sample collection, processing and storage. We discovered a panel of EV-miRNAs that predict disease activity in patients with Lymphoma before, during and after treatment. Nevertheless, key challenges remain before EV-miRNA signatures can be translated into clinical practice.
Key challenges
- Factors determining miRNA variability in plasma/urine are unknown
- Limitations in practical EV isolation/purification methods
- Demonstrating cancer-relatedness of EV-miRNAs in biofluids
- Inaccuracy EV-miRNA profiling techniques due to technical bias
HypothesisReducing technical and biological noise will unleash the promise of cell-freemiRNA as liquid biopsy strategy in clinical practice.
Objectives
1) Develop a practical, reproducible method for EV isolation and EV-miRNA extraction compatible with small RNAseq profiling and IVD-compliant qRT-PCR analysis
2) Demonstrate feasibility of a glycomics strategy to enrich for tumor-derived EV-miRNAs in plasma of patients with Lymphoma
3) Develop an unbiased EV-miRNAseq method, design and apply ‘calibrator spike-inns’ to guide quantitative bioinformatics data acquisition
4) Evaluate and develop machine learning and statistical classifier models for discovery and validation of EV-miRNA signatures/panels
| Short title | AQrate |
|---|---|
| Acronym | AQrate |
| Status | Finished |
| Effective start/end date | 4/01/2021 → 31/01/2023 |