The leaders of MICROB-PREDICT's 11 work packages, including research (WP1-7), ethics (WP8 and WP11), communication, training & exploitation (WP9), and project management (WP10).
MICROB-PREDICT consists of seven different scientific work packages (WPs) which interact with each other, two ethics WPs, the WP for communication, training & exploitation, and the project management WP. Briefly, characterization and harmonization of clinical cohorts with already existing data and samples yet to be analysed build WP1. The de novo analysis of the samples including microbiota and host multi-omics (WP2, WP3) will deliver deep and holistic insight into the microbiome composition, functionalities and microbiome-host interaction. These data together with the knowledge generated in WP6, using in vitro and in vivo models, will form the basis for better understanding of the microbiome functionalities and microbiome-host interaction and will deliver rationales for identification of novel targets and development of novel treatments.
The data generated in WP2 and WP3, together with previously existing data harmonized in WP1, represent the key substance of WP4, which will integrate and model the de novo generated data to identify biomarkers or signatures, which will be validated in silico by the existing data. The next level of validation will consist of samples from independent patients and cohorts, which will then be performed using cheaper and easy-to-use methods, as well as novel cost-effective nanobiosensors in preparation for the up-scaling of these tools in clinical studies (WP5).
WP7 will perform the first clinical trial using a personalized medicine approach for the treatment response in human cirrhosis. WP11 is responsible for strict compliance with ethics guidelines. Health ethics and economics (WP8) will answer questions arising from the use of personalized medicine in these vulnerable patients and elaborate the improvement of the societal and health care burden of the disease. Having on board the stakeholders representing patients, industry and academia, the dissemination activities (WP9) will start early in the project and will cover social media approaches at a layperson’s level all the way to the clinical and scientific guideline improvements at scientific community levels.
All activities will be overseen by WP10 (management).
Clinical, genetic, expositional and geographic characterization of existing dataMore information
Lead beneficiary: UNIDEB
The aims of WP1 are to harmonize the available clinical and biological data (meta-data and microbiome-, other omics-datasets) of previously established large international patient cohorts with various stages of liver disease and healthy controls, to transfer the collected data and biological samples to the partners responsible for the analysis in WPs 2, 3, 4, and 5.
Characterization of the microbiomeMore information
Lead beneficiary: EMBL
The main objectives of WP2 are: (a) to achieve longitudinal whole metagenome shotgun sequencing (WMGS) in existing and novel cohorts; (b) to generate for a subcohort in a coordinated way relevant multi-omics data revealing in-depth knowledge on microbiome functionalities in different body sites; (3) to deliver the basis for identification of biomarkers, which can guide prognostic and therapeutic clinical decisions.
Proteomics and metabolomics of host and microbiomeMore information
Lead beneficiary: MPG
Besides structure and dynamics of genetic material of the microbiome (WP2), WP3 will assess the interplay between host and the gut reflected by changes or synergy in proteome and metabolome in decompensated and ACLF patients.
Data management, integration and systems modellingMore information
Lead beneficiary: UCPH
WP4 aims to manage, integrate and analyse host-microbial multi-omics data to characterize the oral-gut-liver-blood axis in decompensated cirrhosis and ACLF towards early diagnosis, patient stratification, and treatment options.
Validation of biomarker candidates and biosensor developmentMore information
Lead beneficiary: CEA
The novel biomarkers for prediction of decompensation and ACLF development, as well as the response to treatments (Rifaximin and Albumin), must be validated and also integrated to useful tools for end-users to improve personalized medicine. Therefore, molecular signatures coming from metabolomic, proteomic and metagenomics experiments will be obtained using analytical tools dedicated to global and semi-quantitative approaches. Their relevance in terms of specificity and sensitivity towards pathology or a syndrome needs to be confirmed on validation cohorts. To reach this goal, quantitative assays, targeted on a selected number of molecules, will be used in WP5. This is more cost effective and less time consuming than global approaches, and is easy to implement by clinical chemistry laboratories. Thereafter, the most promising biomarkers have to be extensively used and clinically validated before their approval by regulatory agencies, requiring the development of rapid tests and biosensors that can be implemented in clinical units at the bedside.
In vitro and in vivo experimental validation of targetsMore information
Lead beneficiary: GUF
WP6 aims to uncover the mechanisms by which Rifaximin and albumin interact with microbiota, cells of the gut-liver axis and rodent models. Both drugs are suggested to beneficially influence disease progression in cirrhosis, however, mechanisms of action are unknown. Rifaximin is a non-resorbable antibiotic and will be investigated in gut microbiota and cells of gut epithelium. Albumin circulates in the body and is excreted in the gut in cirrhosis and will be investigated in immune, hepatic and intestinal cells, as well as in gut microbiota. Therefore, this WP aims to unveil the mechanisms by which Rifaximin and albumin might be beneficial.
Clinical validation of signature guided interventions (ALB-TRIAL)More information
Lead beneficiary: OUH
The overall objective of WP7 is to validate the biomarkers and biosensors from WP5 in a randomised clinical trial in patients stratified by the treatment response to albumin. The aim is to provide clinical tool for personalized treatment with albumin that can detect high-risk patients who are likely to benefit from treatment, and those who are unlikely to benefit from treatment. WP7 will thereby accelerate the development of biomarkers to be ready for implementation in clinical practice and enable personalised medicine.
Ethics, health, and socio-economicsMore information
Lead beneficiary: UB
MICROB-PREDICT is a multidisciplinary consortium including stakeholders of patients, academia and industry and includes a broad and complex spectrum of methods and tasks. Therefore, several important ethical, legal and socioeconomic issues arise in this project, which will be addressed by this work package and can be summarized in the following main objectives of this WP:
- To develop and implement ethical and legal issues linked to the collection, analysis, transfer and use of human and animal data and samples
- To develop and implement ethical and societal issues related to patients with decompensated cirrhosis
- To compute the economic impact of decompensated cirrhosis in Europe, regional differences and project the effect of MICROB-PREDICT on the methodological changes and health-care costs
Dissemination, training, communication, exploitation and guideline developmentMore information
Lead beneficiary: LUMC
The objective of WP9 is the development and execution of a communication strategy and dissemination plan aimed at outreaching the potential stakeholders of the EU member states, namely patients, health care professionals, regulatory agencies, politicians as well as healthcare insures, both public and private providers.
Ethics requirementsMore information
Lead beneficiary: EF CLIF
This work package sets the ethics requirements that the project must comply with, and ensures proper compliance by all partners throughout the runtime of the project.
Project managementMore information
Lead beneficiary: EF CLIF
Effective project management is a central element of successful research. This is because large research projects entail a lot of administrative work. WP10 will take care of MICROB-PREDICT achieving its objectives and delivering its milestones and deliverables in time, and maintaining oversight of the budget and quality – all in line with the contractual provisions.