Federated artificial intelligence for privacy-preserving international stratification of colorectal cancer patients

Informations projet

Microb-AI-ome

N° de convention de subvention: 101079777

DOI

10.3030/101079777

Date de signature de la CE 16 Mars 2023

Date de début 1 Avril 2023

Date de fin 31 Mars 2028

Financé au titre de

• Health

Coût total

€ 5 996 700,25

Contribution de l’UE

€ 5 996 700,25

Coordonné par

UNIVERSITY OF HAMBURG
Germany

Periodic Reporting for period 2 - Microb-AI-ome (Federated artificial intelligence for privacy-preserving international stratification of colorectal cancer patients)

Période du rapport: 2024-10-01 au 2026-03-31

Résumé du contexte et des objectifs généraux du projet

In the EU, 1 in 35 women and 1 in 23 men will be diagnosed with colorectal cancer (CRC) in their life span (ca. 340,000 cases and 156,000 deaths in 2020) causing an annual economic burden of ca. 20 billion EUR. Identifying CRC early enables better treatment options. Screening usually entails a quantitative faecal immunological test (FIT) to predict the need of colonoscopy for the detection of colorectal lesions, an expensive and invasive procedure. We aim to predict this need with specificity increased by >20 percentage points by using metagenomic microbiomes. We hypothesise that computational microbiome profiles extracted using artificial intelligence (Al) technology will also allow for optimised personal therapy stratification. However, clinicians do not have access to broad microbiome datasets. With Microb-AI-ome, we will develop a novel kind of computational stratification technology to enable microbiome-enhanced precision medicine of CRC. Metagenomic microbiome data that has been generated to date is distributed over many national registries, and privacy regulations are hindering its effective integration. With Microb-AI-ome, we will overcome this barrier by establishing the first privacy-preserving federated big data network in CRC research. We will integrate isolated, national databases into one international federated database network - rather than a cloud - covering metagenomes for over 5,000 individuals screened for CRC, and an expected total of 100,000 by 2026. Microb-AI-ome ensures that no sensitive patient data will leave the safe harbours of the local databases while still allowing for the classification of clinical CRC phenotypes, which we will demonstrate in clinical practice allowing regulatory bodies to adopt evidence-based guidelines. Our consortium combines expertise in CRC and its treatment, microbiomics, artificial intelligence, software development, and privacy protection to close the gap between privacy and big data in international medical research.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

In the second period, the Microb-AI-ome consortium finished the prototype of the federated database network Microb-AI-Net. The prototype was sandboxed and containerized, extended with time series support and intensely tested. Microb-AI-Net is the foundation for federated training of the AI models, the so-called Microb-AIs. To this end, the evaluation of batch effect correction methods has been finalized and a preprocessing and machine learning pipeline for training AI stratification models has been established. This pipeline has been started to be transferred to a federated setting, including analytic support that the centralised and federated analysis pipelines output equivalent results. Patient recruitment in France and Ireland has continued. It has reached ca. 50% of the recruitment target in Ireland. In France, recruitment has been expanded from French Gut colo to the entire French Gut cohort and ca. 2,700 participants have been recruited to date in France. In parallel, contact with critical national and international regulatory bodies has been maintained to pave the way for update of Microb-AI-ome's results into future clinical and screening practice. Work on the legal and ethical framework as well as the Combined Impact Assessment for Microb-AI-ome has continued. Dissemination and communication activities have intensified including an extended digital presence, continuous outreach via the project website and social media and the generation of new communication materials. At the same time, future sustainablity of the project has remained a central point of consideration culminating in an updated exploitation plan, a map of the key market players as well as the survey of the current patent landscape. Throughout all of the second period, the project management infrastructure was maintained to help optimally support the project's work in accordance with it's objectives and contractual obligations.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

Microb-AI-ome adresses all three of the expected outcomes as stated in the work programme:

Clinical researchers use effective health data integration solutions for the classification of the clinical phenotypes - Microb-AI-Net will provide an infrastructure to CRC clinicians and researchers that, for the first time, allows the integrated analysis of international microbiome and healthcare data for the training of CRC stratification models.

Researchers and/or health care professionals use robust and validated data-driven computational tools to successfully stratify patients - The trained Microb-AIs for prediction of a colonoscopy based on microbiome data will be validated for their robustness and stratification performance as part of the project and made available through the CRC Stratifier software. Once validated, these models can be integrated into medical guidelines, where appropriate.

Regulatory bodies approve computer-aided patient stratification strategies to enable personalised diagnosis and/or personalised therapy strategies. Health care professionals adopt evidence-based guidelines for stratification-based patient management superior to the standard-of-care. To prepare for the clinical deployment of Microb-AI-ome beyond the project runtime, we will develop protocols that comply with both EU and US regulatory standards, particularly in the final phase of clinical deployment. We will seek in-house accreditation for our protocols according to ISO 15189 and Clinical laboratory ISO 13485 standards for in vitro diagnostics. This will ensure that we meet the relevant CLIA and EU lab accreditation requirements, EU/CE mark standards, and FDA requirements. During the final clinical validation phase, we will implement a Quality Management System (QMS) and data handling procedures to comply with ISO 13485, ISO 15189, and 21 CFR 820, as well as Regulation (EU) 2017/746. We will also ensure compliance with evolving medical diagnostic regulations and with GDPR requirements.