Periodic Reporting for period 1 - Disc4All (Training network to advance integrated computational simulations in translational medicine, applied to intervertebral disc degeneration)
Reporting period: 2020-11-01 to 2022-10-31
The European community requires a new generation of researchers who can work across the boundaries of traditional disciplines, integrating experimental and in silico approaches to understand and manage highly prevalent multifactorial disorders, such as musculoskeletal disorders. The Disc4All training network utilises intervertebral disc degeneration (LDD) leading to low back pain (LBP) as a relevant application for the integration of data and computational simulations in translational medicine, to enable rational interpretations of the complexity of the interactions that eventually lead to symptoms.
LBP is the largest cause of morbidity worldwide, being the 4th leading cause of DALYs among Non-Communicable Diseases, already for the population between 25 and 49 years of age, according to the 2019 Global Disease Burden Report. Yet, there remains controversy as to the specific cause leading to poor treatment options and prognosis. LDD is reported to account for 50% of LBP in young adults, but the interplay of factors from genetics, environmental, cellular responses and social and psychological factors is poorly understood. Unfortunately, the integration of such data into a holistic and rational map of degenerative processes and risk factors has not been achieved, requiring creation of professional cross-competencies, which current training programmes in biomedicine, biomedical engineering and translational medicine fail to address, individually.
Disc4All aims to tackle this issue through collaborative expertise of clinicians; computational physicists and biologists; geneticists; computer scientists; cell and molecular biologists; microbiologists; bioinformaticians; and industrial partners. It provides interdisciplinary training in data curation and integration; experimental and theoretical/computational modelling; computer algorithm development; tool generation; and model and simulation platforms to transparently integrate primary data for enhanced clinical interpretations through models and simulations. Complementary training is offered in dissemination; project management; research integrity; ethics; regulation; policy; business strategy; and public and patient engagement. The Disc4All ESRs will provide a new generation of internationally mobile professionals with unique skill sets for the development of thriving careers in translational research applied to multifactorial disorders.
LBP is the largest cause of morbidity worldwide, being the 4th leading cause of DALYs among Non-Communicable Diseases, already for the population between 25 and 49 years of age, according to the 2019 Global Disease Burden Report. Yet, there remains controversy as to the specific cause leading to poor treatment options and prognosis. LDD is reported to account for 50% of LBP in young adults, but the interplay of factors from genetics, environmental, cellular responses and social and psychological factors is poorly understood. Unfortunately, the integration of such data into a holistic and rational map of degenerative processes and risk factors has not been achieved, requiring creation of professional cross-competencies, which current training programmes in biomedicine, biomedical engineering and translational medicine fail to address, individually.
Disc4All aims to tackle this issue through collaborative expertise of clinicians; computational physicists and biologists; geneticists; computer scientists; cell and molecular biologists; microbiologists; bioinformaticians; and industrial partners. It provides interdisciplinary training in data curation and integration; experimental and theoretical/computational modelling; computer algorithm development; tool generation; and model and simulation platforms to transparently integrate primary data for enhanced clinical interpretations through models and simulations. Complementary training is offered in dissemination; project management; research integrity; ethics; regulation; policy; business strategy; and public and patient engagement. The Disc4All ESRs will provide a new generation of internationally mobile professionals with unique skill sets for the development of thriving careers in translational research applied to multifactorial disorders.
Since it started, Disc4All has successfully collected hundreds of medical image and molecular data, from existing population cohorts such as the Northern Finland Birth Cohorts and the Twins UK cohort, and from a patient cohort built during a former European project (MySpine FP7-269909). This material is permitting the construction of advanced classifiers of different intervertebral disc degeneration phenotypes, highlighting the need for improvement of current disc degeneration grading systems to progress low back pain patient stratification. As the project uses bioinformatics methods to relate molecular information to clinical information such as comorbidities, we expect to improve the capacity to generate differential diagnoses of intervertebral disc degeneration. This shall support the development of improved personalized treatments, in the future.
Specific modelling and simulation technologies have already been developed during the project, including the personalised modelling of the intervertebral disc multi-physics behaviour, and the simulation of disc cell activity in presence of different types of cell stimulators. The cell activity models are being nourished by specific cell culture models perturbed by different biochemical and mechanical environments. Thanks to extended cell regulation computational models, cell sample proteome measurements are informing about possible differential activations of cell regulation pathways, depending on the experimental perturbation. In the next steps of the project, disc cell and organ model simulations will provide synthetic data, that will be tested against the capacity to enhance real world phenotype and molecular data for advanced stratification and risk factor identification in disc degeneration and low back pain. To cope with the computational burden, calculation software is being adapted to high performance computing, for the use of distributed supercomputing infrastructures. Remarkably, the project has already delivered the first versions of the data models and integration platform, for the exploitation of the Disc4All tools by third parties. Reusable versions are planned to be shared totally or partially by the end of the project.
Specific modelling and simulation technologies have already been developed during the project, including the personalised modelling of the intervertebral disc multi-physics behaviour, and the simulation of disc cell activity in presence of different types of cell stimulators. The cell activity models are being nourished by specific cell culture models perturbed by different biochemical and mechanical environments. Thanks to extended cell regulation computational models, cell sample proteome measurements are informing about possible differential activations of cell regulation pathways, depending on the experimental perturbation. In the next steps of the project, disc cell and organ model simulations will provide synthetic data, that will be tested against the capacity to enhance real world phenotype and molecular data for advanced stratification and risk factor identification in disc degeneration and low back pain. To cope with the computational burden, calculation software is being adapted to high performance computing, for the use of distributed supercomputing infrastructures. Remarkably, the project has already delivered the first versions of the data models and integration platform, for the exploitation of the Disc4All tools by third parties. Reusable versions are planned to be shared totally or partially by the end of the project.
Beyond a training program that is increasing the potential of a new type of translational researchers and positively contribute to structuring doctoral training while strengthening the research innovation landscape at the European level, Disc4All is working on concrete exploitable results for its beneficiaries and the society at large, regarding data integration and computational simulations in translational medicine.
One main outcome of the project is a simulation platform offering access to the models and data contained therein, with the possibility of running further simulations and analyses. For the users of the platform, in other words the researchers, regulators, and doctors, the value offered is in modelling and simulation, pathway and data integration, knowledge extraction and biomarker identification. In the future, customers could come from backgrounds such as government, healthcare providers, medical equipment manufacturers, and the scientific community at large. But more immediately, the Disc4All infrastructure of data integration and systems modelling and simulations in intervertebral disc degeneration shall definitely contribute to open science, in the form of readily usable tools in scientific and clinical research.
New understanding about the origin, biology and treatment for low back pain and disc degeneration will emerge from the ‘cross-pollination’ of the input from all 15 research students until the end of the project.
Disc4All promotes the development of careers in translational research and provides a new generation of professionals with international mobility equipped with a set of unique capabilities to tackle the prevention and management of highly complex disorders through data and technology.
In particular, this project will result in beta tools for advanced diagnosis and stratification of low back pain patients, based on medical images, pain and molecular data, enhanced by model and simulation results, enabling targeted therapies.
At the socio-economic level, the Disc4All aims to raise awareness about low back pain and spinal health and promote improved self-monitoring and management, for both prevention and curation. Self-management includes the consciousness and basic knowledge of the capability to act on different factors, such as lifestyle, either preventively or to improve the outcome of a clinical therapy, through daily actions.
One main outcome of the project is a simulation platform offering access to the models and data contained therein, with the possibility of running further simulations and analyses. For the users of the platform, in other words the researchers, regulators, and doctors, the value offered is in modelling and simulation, pathway and data integration, knowledge extraction and biomarker identification. In the future, customers could come from backgrounds such as government, healthcare providers, medical equipment manufacturers, and the scientific community at large. But more immediately, the Disc4All infrastructure of data integration and systems modelling and simulations in intervertebral disc degeneration shall definitely contribute to open science, in the form of readily usable tools in scientific and clinical research.
New understanding about the origin, biology and treatment for low back pain and disc degeneration will emerge from the ‘cross-pollination’ of the input from all 15 research students until the end of the project.
Disc4All promotes the development of careers in translational research and provides a new generation of professionals with international mobility equipped with a set of unique capabilities to tackle the prevention and management of highly complex disorders through data and technology.
In particular, this project will result in beta tools for advanced diagnosis and stratification of low back pain patients, based on medical images, pain and molecular data, enhanced by model and simulation results, enabling targeted therapies.
At the socio-economic level, the Disc4All aims to raise awareness about low back pain and spinal health and promote improved self-monitoring and management, for both prevention and curation. Self-management includes the consciousness and basic knowledge of the capability to act on different factors, such as lifestyle, either preventively or to improve the outcome of a clinical therapy, through daily actions.