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Derivation of pediatric sepsis phenotypes using machine learning applied to clinical, functional and genomic data from the swiss pediatric sepsis study

English title Derivation of pediatric sepsis phenotypes using machine learning applied to clinical, functional and genomic data from the swiss pediatric sepsis study
Applicant Schlapbach Luregn
Number 201060
Funding scheme Project funding
Research institution Pediatric and Neonatal Intensive Care Unit Children`s Research Center University Children's Hospital Zurich
Institution of higher education University of Zurich - ZH
Main discipline Paediatrics
Start/End 01.04.2021 - 31.03.2024
Approved amount 930'302.00
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All Disciplines (5)

Discipline
Paediatrics
Information Technology
Immunology, Immunopathology
Internal Medicine
Medical Statistics

Keywords (10)

mortality; neonate; genomics; primary immunodeficiency; child; bacteremia; immunology; organ dysfunction; infant; sepsis

Lay Summary (German)

Lead
Sepsis ist eine der häufigsten Gründe für Mortalität und Morbidität bei Kindern. Weltweit versterben jeden Jahr 3 Mio Kinder an einer Sepsis. Sepsis ist definiert als lebensgefährliches Organversagen infolge schwerer Infektionen. Die genetischen und biologischen Ursachen, die zum Organversagen bei Sepsis führen, sind bisher zu wenig untersucht. Dieses Projekt wird mithilfe Artifizieller Intelligenz versuchen, besser zu verstehen, weshalb gewisse Kinder eine Sepsis entwickeln.
Lay summary

Inhalt und Ziele des Forschungsprojekts

Sepsis verursacht mehr Todesfälle bei Kindern jedes Jahr als Verkehrsunfälle oder viele kindliche Krebsarten. Dennoch bleibt unser Verständnis der Ursachen, die dazu führen, dass ein Kind eine schwere Sepsis entwickelt, begrenzt.

Die renommierte Schweizer Pädiatrische Sepsisstudie hat 1204 Kinder mit Blutkultur-bestätigter Sepsis in 10 Schweizer Kinderspitälern eingeschlossen. Diese Studie hat gezeigt, wie häufig Sepsis bei Kindern in der Schweiz auftritt und zu welchen Folgen sie führt.

Im Rahmen des neuen Forschungsprojekts werden nun erweiterte genetische und immunologische Untersuchungen in den Studienproben durchgeführt, so genannte «OMICs». Mit neuartigen Verfahren aus dem Bereich der Artifiziellen Intelligenz hat das Projekt zum Ziel, Muster und Mechanismen zu erkennen, die zur schweren Sepsis bei Kindern führen.

 

Wissenschaftlicher und gesellschaftlicher Kontext des Forschungsprojekts

Sepsis ist eine der Hauptursachen für Mortalität und Morbidität bei Kindern in der Schweiz und global. Dieses Forschungsprojekt baut auf einer gut etablierten Schweizer Kohortenstudie auf und verbindet Experten in den Bereichen Pädiatrie, Genomik, Immunologie und Bioinformatik aus einem Forschungsnetzwerk hervorragender Qualität. Die Studienresultate sollen das Verständnis der Mechanismen der Sepsis bei Kindern verbessern und dadurch helfen, in Zukunft bessere Diagnostik und Therapie zu entwickeln.

 

Direct link to Lay Summary Last update: 05.06.2021

Lay Summary (French)

Lead
La septicémie est une des causes les plus fréquentes de mortalité chez les enfants. Au niveau mondial on estime à trois millions par an le nombre d’enfants qui décèdent des suites d’une septicémie. La septicémie est défini comme un syndrome entraînant un dysfonctionnement vital des organes. À ce jour les mécanismes génétiques et biologiques de ce dysfonctionnement sont mal connus. A l’aide de l’intelligence artificielle appliquée aux données cliniques, génomiques et immunologiques, ce projet a pour objectif de comprendre pourquoi des enfants développent le sepsis.
Lay summary

Contenu et objectifs du projet de recherche

Le sepsis cause plus de décès chez les enfants par an que les accidents de la route ou le cancer. Pourtant nous connaissons mal les raisons pour lesquelles un enfant développe un sepsis grave, voire en décède.

L’étude suisse pour le sepsis pédiatrique est une cohorte nationale observationnelle prospective multicentrique qui englobe les 10 hôpitaux pédiatriques suisses, Au cours des dernières années, 1204 enfants présentant une septicémie bactérienne ont été enrôlés dans l’étude de cohorte. Cette étude montre la fréquence du sepsis chez les enfants en Suisse.

Nous envisageons à présent de réaliser des analyses génétiques et fonctionnelles additionnelles, nommé « OMICs ». Grâce à des méthodes innovantes soutenues par des méthodes computationnelles (« l’intelligence artificielle »), le projet cherche à mettre en évidence des modèles explicatifs des raisons pour lesquelles certains enfants développent une maladie grave pendant une septicémie.

 

Contexte scientifique et sociétal du projet de recherche

La septicémie est une cause importante de mortalité et de morbidité infantile en Suisse et dans le monde. Notre projet peut bénéficier d’une étude de cohorte suisse exceptionnelle et de l’association des réseaux d’experts scientifiques suisses d’excellence en pédiatrie, génomique, immunologie et informatique biologique. Les résultats de l’étude devraient servir à améliorer les connaissances du mécanisme de la septicémie chez les enfants et aider au développement de nouvelles approches de la maladie.

Direct link to Lay Summary Last update: 05.06.2021

Lay Summary (Italian)

Lead
La sepsi costituisce la causa più frequente di mortalità e morbilità in età infantile. A livello mondiale muoiono ogni anno 3 milioni di bambini per Sepsi. La sepsi è definita un guasto organico dovuto a gravi infezioni. Le cause genetiche e biologiche di questo guasto organico che portano alla sepsi sono state finora scarsamente analizzate. Con l’ausilio dell’intelligenza artificiale questo Progetto cercherà di comprendere meglio il perché alcuni bambini sviluppano una sepsi.
Lay summary

Soggetto e obiettivi del Progetto di ricerca

 

Ogni anno la sepsi causa più morti di bambini degli incidenti stradali o di molte forme di neoplasia infantile. Ciononostante, la nostra comprensione del perché un bambino sviluppi una Sepsi grave, rimane limitata.

Il rinomato studio pediatrico svizzero della sepsi ha esaminato 1204 bambini affetti da Sepsi comprovata da emocoltura in 10 ospedali pediatrici svizzeri. Questa ricerca ha mostrato quanto sia frequente in Svizzera la sepsi infantile e quali possono essere le conseguenze. Nel quadro di questo nuovo progetto di ricerca verranno eseguiti esami genetici e immunologici più estesi, i cosiddetti “OMICs”. Grazie ai nuovi procedimenti nell’ambito dell’intelligenza artificiale il progetto intende determinare il modello e i meccanismi che causano la sepsi infantile grave.

 

Contesto scientifico e sociale del Progetto di ricerca

 

Come si è visto la sepsi è la causa principale di mortalità e morbilità tra i bambini in Svizzera e a livello globale. Questo progetto di ricerca si basa su uno studio di coorte svizzero ben costruito al quale partecipano esperti nell’ambito della pediatria, della genomica, dell’immunologia e della bioinformatica, ricercatori di una rete di qualità eccellente. I risultati dello studio dovrebbero migliorare la comprensione dei meccanismi della sepsi nei bambini, facilitando così a sviluppare in futuro una diagnostica e una terapia migliori.


Direct link to Lay Summary Last update: 05.06.2021

Lay Summary (English)

Lead
Sepsis is a leading cause of death and disability in children globally accounting for three million childhood deaths each year. Sepsis is defined as “detrimental response of the body to infection leading to life-threatening failure of organ”. The biological and genetic mechanisms underlying sepsis in children are poorly understood. Using machine learning applied to clinical, genomic, and immunologic data, this project aims to discover why some children develop sepsis.
Lay summary

Content and aims of the research proposal:
Sepsis kills more children every year than road traffic accidents or than diseases such as childhood cancer. Yet, our understanding of why some children become extremely unwell or die doe to sepsis remains limited.

The landmark Swiss Pediatric Sepsis Study is a prospective national observational multicenter cohort study including all 10 major Swiss children`s hospitals and has recruited 1204 children with blood culture-proven bacterial sepsis over the past years. The study has highlighted the high burden of sepsis in children.

Using this world-wide largest study on blood culture-confirmed sepsis in children we will now perform additional genetic and functional analyses, so called “OMICs”. Using novel innovative computational methods (“artificial intelligence”) we seek to discover patterns which explain why some children become severely ill in the course of sepsis.

Scientific and societal context of the research project:

Sepsis represents a leading cause of childhood mortality and morbidity in Switzerland, and globally. This study will benefit from a unique cohort and is building on the combined expertise in pediatrics, genomics, immunology, and computational science across a high performing Swiss research network. The study findings are expected to improve our understanding of sepsis in children, and to help to develop novel approaches to the disease.

Direct link to Lay Summary Last update: 05.06.2021

Responsible applicant and co-applicants

Employees

Project partner

Associated projects

Number Title Start Funding scheme
153158 Swiss Pediatric Sepsis Study - a national prospective cohort study to assess epidemiology, novel immunodeficiencies and the impact of genetic variation on susceptibility to sepsis in children 01.07.2014 Project funding (special)

Abstract

Sepsis is severe infection, leading to life-threatening shutdown of organs. Sepsis represents a leading cause of death and disability in children: Over three million children die each year due to sepsis and one out of three childhood sepsis survivors will suffer from ongoing health problems. In fact, the risk of acquiring sepsis is never as high as during early childhood. A recent resolution by the WHO endorsed by Switzerland highlighted that sepsis is a global threat, demanding urgent actions to improve understanding and therapy of sepsis. While it is well known that bacteria and other pathogens such as viruses cause infections, the mechanisms underlying the severe response of the body to infection which ultimatively results in sepsis are not well understood. There is a need for studies in children with sepsis which investigate the genetic and immunologic features of the disease.The landmark Swiss Pediatric Sepsis Study is a national observational multicenter cohort study including all 10 major children`s hospitals which recruited 1204 children with bacterial sepsis in Switzerland. The purpose of the new project is to investigate the clinical, genomic, and functional information from this unique study. We suspect that different children develop different patterns of their body`s response to infection. Using new methods, such as Artificial Intelligence, we aim to find groups of children which are particularly unwell due to sepsis, and which are more likely to one day benefit from specific interventions. For this purpose, we will investigate the genes involved, as well as markers of the body`s response to infection.As a first objective, we will explore the role of genetic variation to understand why some children are very vulnerable to sepsis. As a second objective, we will then compare how the immune system of different children responds to sepsis. It is possible that we may find that some children with sepsis suffer from underlying alterations in their immune system, which makes them more susceptible to sepsis.Finally, using new computational methods, so called machine learning, we will try to integrate the wealth of genetic, clinical, and functional data to gain a completely new perspective on why some children become severely unwell due to sepsis.This world-wide largest contemporary study on bacterial sepsis in children has the potential to identify key mechanisms determining sepsis risk and sepsis outcomes in children. Our hope is that it can thereby improve our understanding of the progression from infection to sepsis. Ultimately, we hope to gain a better understanding of the individual susceptibility to sepsis. Thereby, we hope to help to enable better treatment of children with sepsis in the future, for example through personalized medicine.
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