What is the issue?
Infections with the Respiratory Syncytial Virus (RSV) occur worldwide and are seasonally more frequent during the winter months. By the end of the second year of life, almost all children had contact with the pathogen at least once. In most cases, the infection of small children leads to a mild cold that heals untreated. However, in about 1% of children, the progression of the disease leads to complications that result in inflammation of the upper and lower respiratory tract. These children are hospitalized and may need to be ventilated, in rare cases the infection can be fatal.
Currently there are no active vaccines available to protect against infection with the virus. Passive immunization with a virus-neutralizing antibody is offered to children who are at high risk for a severe infection. These risk groups include, for example, premature babies who will be protected from RSV infection in their first year of life by the antibody. However, even children without known risk factors repeatedly develop severe RSV infections. The factors that cause such severe RSV infections are not fully understood. Seriously ill children are treated symptomatically, since a causal, directly antiviral therapy is not available. Research is therefore concentrating on the development of new therapies and an active vaccine. Thus, the identification of risk factors contributing to the development of an infection should help to provide optimal protection for susceptible children and to find starting points for a therapy.
What are our goals?
In the INDIRA project, we want to investigate the causes that are responsible for different RSV disease progressions among young children. For example, we want to understand which genetic factors contribute to the severe pathology in some children, while other children only develop a mild cold. We want to learn how such genetic traits influence immune control and/or virus replication and how the course of the disease is controlled. In the long term, we want to use computer models and bioinformatic methods to develop diagnostic procedures from this data that can make a prognosis about a child's risk of infection using just a few markers. To achieve this goal, we have developed a multidisciplinary research approach that brings together physicians, researchers and computer experts. In addition, we are investigating whether factors that influence the course of the disease are suitable for the development of a therapy.
How do we reach our goals?
To achieve this goal, we have developed a multidisciplinary research approach that brings together physicians, researchers and computer experts. The basis of the research project is the development of a complete integration of clinical, molecular, genetic and metabolic data in order to gain a deeper understanding of the infection process. By using state-of-the-art computer-based methods (artificial intelligence and machine learning), this complex multidimensional information will be processed to unlock the individual determinants that contribute to the onset of infection.
The project builds on clinical data obtained from anonymous seasonal patients affected by RSV. The initial data originate from pre-existing cohorts such as the IRIS cohort and data from the cluster of excellence RESIST. For the season 2019 - 2020 and 2020 – 2021, new cohorts will be generated for the INDIRA project and the generated data will produce the main body of the project analysis.
For the respective cohorts, the analysis will start from the clinical data acquired for each patient and their integration with genomic and metabolic analyses. In parallel, in vitro studies will be carried out that will generate additional genetic and metabolic information on the RSV infection. Finally, the data shall be analyzed and integrated through calculation procedures based on artificial intelligence and machine learning.
Prof. Dr. Thomas Pietschmann
Institute for Experimental Virology TWINCORE - Centre for Experimental and Clinical Infection Research Feodor-Lynen-Str. 7-9 30625 Hannover Germany
Phone: +49 511 22 00 27-130
Fax: +49 511 22 00 27-139
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Dr. Robert Geffers
HZI | Technology Platform Genome Analytics
Phone: +49 531 6181-3058
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Prof. Dr. Gesine Hansen
MHH | Clinic for Pediatric Pneumology, Allergology and Neonatology
Phone: +49 511 532 - 9138
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Prof. Dr. Karsten Hiller
TU Braunschweig | Department of Bioinformatics and Biochemistry
Phone: +49 531 391-55201
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Prof. Dr. Lars Kaderali
University Medicine Greifswald | Institute of Bioinformatics
Phone: +49 3834 86-5441
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Prof. Dr. Jörn Ostermann
LUH | Institute of Information Processing
Phone: +49 511 762-5316
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Prof. Dr. Jörg Overmann
DSMZ | Department of Microbial Ecology and Diversity
Phone: +49 531 2616-352
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Prof. Dr. Bodo Rosenhahn
LUH | Institute of Information Processing
Phone: +49 511 762-5316
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Prof. Dr. Chris Lauber
TWINCORE | Research Group Computational Virology
Phone: +49 511 220027-238
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Dr. Emmanuel Saliba
HIRI | Research Group Single-Cell Analysis
Phone: +49 931 31-81341
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Involved Institutions
TRAIN (Translational Alliance in Lower Saxony), CiiM (Centre for individualized infection Medicine), MHH (Medical School Hannover), HZI (Helmholtz Centre for Infection Research),TU-BS (Technical University Braunschweig), Leibniz Institute DSMZ (German Culture Collection of Microorganisms and Cell Cultures), TWINCORE – Centre for Experimental and Clinical Infection Research, LUH (Leibniz University Hannover)
External Partners: University Medicine Greifswald, HIRI (Helmholtz Institute for RNA-based Infection Research)
Milestones
- The INDIRA consortium met for a kick off meeting in 2019 as well as annual meetings in 2020 and 2021. Between the events, there were meetings among the working groups (Machine Learning, Visual analytics, Proof of Concept and Replica cohort) to organize and coordinate the ongoing analysis.
updated 03/2021