Periodic Reporting for period 1 - EpiPrecise (Epigenetic profiling of menstrual blood for precision cancer detection and prevention)
Periodo di rendicontazione: 2024-04-01 al 2025-09-30
Tackling the growing cancer burden requires a multifactorial approach including understanding the fundamental drivers of cancer development; improving methods for detecting earlier those forms of cancer with the worst prognosis; predicting a person’s risk of developing cancer; and identifying appropriate targets for preventing cancer. One of the biggest obstacles in identifying tailored cancer prevention strategies is a lack of surrogate readout markers reflecting and integrating an individual’s response to the cancer-initiating and cancer-promoting factors that they are exposed to during their lifetime. Our team’s research delivers novel epigenetic tests relating to each of these key areas with an emphasis on women’s health and those who are at an increased risk for cancer due to an underlying condition such as endometriosis. A cellular deconvolution algorithm used to calculate the proportions of cell types within complex, mixed samples, such as cervical swabs, is central to this effort. In this project, we aimed expand this cellular deconvolution algorithm. The expansion included cell types in menstrual blood, which is an important and understudied clinical sample type.
The project focused on extending and technically validating the cellular reference framework required for deconvolution of menstrual blood samples.
Key activities included:
• Analysis of epigenetic data from purified cell populations, including fluorescence-activated cell sorting (FACS)–isolated fractions representing cell types relevant to menstrual blood.
• Curation and integration of publicly available epigenetic datasets, complemented by newly generated reference data, to improve coverage of relevant cellular states.
• Computational extension of the existing deconvolution framework, enabling the inclusion of additional cell types characteristic of menstrual blood.
• Evaluation of the expanded framework to assess its ability to resolve cellular composition in complex mixed samples.
Through these activities, the project achieved its primary technical objective: the successful extension of the cellular deconvolution algorithm to support menstrual blood. This represents an enabling methodological advance that improves the interpretability of epigenetic measurements derived from this biological material.
Outcomes of the Action
By the end of the project, the following outcomes were achieved:
- An expanded cellular deconvolution algorithm applicable to menstrual blood samples.
- High-quality reference epigenetic profiles for additional cell types relevant to women’s health applications.
- A validated methodological foundation for future epigenetic studies that require accurate adjustment for cellular heterogeneity in menstrual blood.
Key activities included:
• Analysis of epigenetic data from purified cell populations, including fluorescence-activated cell sorting (FACS)–isolated fractions representing cell types relevant to menstrual blood.
• Curation and integration of publicly available epigenetic datasets, complemented by newly generated reference data, to improve coverage of relevant cellular states.
• Computational extension of the existing deconvolution framework, enabling the inclusion of additional cell types characteristic of menstrual blood.
• Evaluation of the expanded framework to assess its ability to resolve cellular composition in complex mixed samples.
Through these activities, the project achieved its primary technical objective: the successful extension of the cellular deconvolution algorithm to support menstrual blood. This represents an enabling methodological advance that improves the interpretability of epigenetic measurements derived from this biological material.
Outcomes of the Action
By the end of the project, the following outcomes were achieved:
- An expanded cellular deconvolution algorithm applicable to menstrual blood samples.
- High-quality reference epigenetic profiles for additional cell types relevant to women’s health applications.
- A validated methodological foundation for future epigenetic studies that require accurate adjustment for cellular heterogeneity in menstrual blood.
The project advances the state of the art by extending cellular deconvolution methodologies beyond commonly used sample types to include menstrual blood. This expansion addresses a recognised methodological gap and enables more accurate interpretation of epigenetic data derived from a non-invasive and clinically relevant sample source.
The availability of a deconvolution framework for menstrual blood has the potential to support future research efforts aimed at improving risk assessment, early detection, and prevention strategies in women’s health. By reducing confounding effects introduced by cellular heterogeneity, the approach enhances the analytical resolution of downstream epigenetic analyses without presupposing specific biomarkers or clinical applications.
The results have the potential to:
• Enable more precise epigenetic biomarker discovery by reducing cellular confounding effects.
• Support earlier detection and risk stratification in women with endometriosis.
• Facilitate the development of scalable, non-invasive diagnostic and preventive tools tailored to women’s health.
The results are currently being prepared for publication.
The availability of a deconvolution framework for menstrual blood has the potential to support future research efforts aimed at improving risk assessment, early detection, and prevention strategies in women’s health. By reducing confounding effects introduced by cellular heterogeneity, the approach enhances the analytical resolution of downstream epigenetic analyses without presupposing specific biomarkers or clinical applications.
The results have the potential to:
• Enable more precise epigenetic biomarker discovery by reducing cellular confounding effects.
• Support earlier detection and risk stratification in women with endometriosis.
• Facilitate the development of scalable, non-invasive diagnostic and preventive tools tailored to women’s health.
The results are currently being prepared for publication.