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System analysis of seasonal Influenza - virus transmission and evolution in the City of Basel

English title System analysis of seasonal Influenza - virus transmission and evolution in the City of Basel
Applicant Stadler Tanja
Number 166258
Funding scheme Interdisciplinary projects
Research institution Computational Systems Biology Department of Biosystems, D-BSSE ETH Zürich
Institution of higher education ETH Zurich - ETHZ
Main discipline Infectious Diseases
Start/End 01.04.2016 - 31.12.2019
Approved amount 607'509.00
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All Disciplines (4)

Infectious Diseases
Social geography and ecology
Medical Statistics
Medical Microbiology

Keywords (4)

Epidemiology; Influenza; Evolution; Phylogenetics

Lay Summary (German)

Erkrankungen mit Influenzaviren sind mit hohem Einfluss auf die Gesundheit und Sterblichkeit sowie Gesundheitskosten assoziiert. Die Prävention der Influenzaübertragung hat deshalb eine hohe Priorität in der öffentlichen Gesundheit. Die Faktoren, welche die Übertragung der Grippe in einer Stadt wie Basel beeinflussen, sind aber nicht geklärt.
Lay summary
Im Rahmen unseres interdisziplinären Forschungsprojekts wollen wir die Transmission und Evolution der Influenza der Stadt Basel in Bezug auf patientenspezifischen, geographischen und virologischen Faktoren untersuchen. Insbesondere wollen wir den Einfluss von Kindern auf die Influenza-Ausbreitung quantifizieren. Was ist die Transmissionsrate von Kindern im Vergleich zu Erwachsenen? Evolviert der Influenza-Virus in Kindern neue Varianten gegen die Erwachsene nicht immun sind? Eine Beantwortung dieser Fragen erlaubt es zu evaluieren welche Massnahmen eine Grippe-Ausbreitung eindämmen, und insbesondere, ob eine Influenza-Impfempfehlung für Kinder sinnvoll sein könnte. 

Wir führen einerseits eine Bevölkerungsbefragung in Basel-Stadt zu Influenza durch (Abteilung Humangeographie des Departements Umweltwissenschaften der Universität Basel), und werden andererseits in einer prospektiven klinischen Studie Patientenproben mit Influenza-Viren sowie epidemiologische und demographische Daten sammeln (Abteilung Klinische Mikrobiologie des Universitätsspital Basel, Infektiologie und Vakkzinologie des Universitätskinderspitals beider Basel, universitäres Zentrum für Hausarztmedizin der Universität Basel). Die gesammelten Daten werde mit statistischen Methoden, die im Rahmen dieses Projekts entwickelt werden, ausgewertet (Gruppe Computational Evolution, ETH Zürich in Basel).
Direct link to Lay Summary Last update: 10.11.2016

Responsible applicant and co-applicants



Evaluation of two workflows for whole genome sequencing-based typing of influenza A viruses
Wüthrich Daniel, Lang Daniela, Müller Nicola F., Neher Richard A., Stadler Tanja, Egli Adrian (2019), Evaluation of two workflows for whole genome sequencing-based typing of influenza A viruses, in Journal of Virological Methods, 266, 30-33.
MASCOT: parameter and state inference under the marginal structured coalescent approximation
Müller Nicola F, Rasmussen David, Stadler Tanja (2018), MASCOT: parameter and state inference under the marginal structured coalescent approximation, in Bioinformatics, 3843-3848.


Group / person Country
Types of collaboration
Fred Hutchinson Cancer Research Center United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Universität Basel - Institut Hausarztmedizin Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Stiftung Blutspendezentrum SRK Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Clinical Microbiology, University Hospital Basel Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
UKBB - Universitaetskinderspital beider Basel Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
USB - Universitaetsspital Basel Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Institute Viollier Microbiology Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Special Seminar at the Doherty Institute Individual talk Estimating reassortment networks, events and rates of influenza viruses 06.03.2019 Melbourne, Australia Müller Nicola Felix;
New Zealand Phylogenomics Meeting Talk given at a conference Estimating reassortment rates of segmented viruses from genetic sequence data 11.02.2019 Napier, New Zealand Müller Nicola Felix;
Global Young Scientist Summit Poster Characterising the epidemic spread of Influenza A/H3N2 within a city through phylogenetics 20.01.2019 Singapur, Singapore Müller Nicola Felix;
Evolution conference Talk given at a conference Quantifying migration patterns and transmission fitness variation in pathogen epidemics 19.08.2018 Montpellier, France Stadler Tanja;
Invited Seminar Institute Pasteur Individual talk Pathogen dynamics through a phylogenetic lens 17.05.2018 Paris, France Stadler Tanja;
Invited seminar talk Individual talk Inference of population structure from genetic sequence data 02.02.2018 Ulm, Germany Müller Nicola Felix;
Microbial Source Attribution using Genomic Data Talk given at a conference Phylodynamics in structured Populations 26.05.2016 London, Great Britain and Northern Ireland Stadler Tanja; Müller Nicola Felix;


Title Date Place
Taming the BEAST 23.04.2018 Oberaegeri, Switzerland
Taming the BEAST 26.06.2016 Engelberg, Switzerland

Communication with the public

Communication Title Media Place Year
Media relations: radio, television Grippe-Umfrage in Basler Quartieren SRF German-speaking Switzerland 2016
Media relations: print media, online media Grossoffensive gegen die Grippe BAZ German-speaking Switzerland 2016
New media (web, blogs, podcasts, news feeds etc.) Influenza in Basel Website Gruppe Stadler - Information International 2016


Title Year
ETH representatives to the Global Young Scientist Summit (GYSS), 20-25 January 2019 in Singapore. Includes travel stipend. 2019
IDEAS Research Exchange Grant "Analysis of the global spread of the different Influenza strains using novel phylogeographic methods" 2017

Use-inspired outputs


Name Year

Associated projects

Number Title Start Funding scheme
192515 Screening for multi-drug resistant pathogens: usage of rapid metagenomic technologies for screening and surveillance 01.08.2020 Project funding (Div. I-III)


Up to 500’000 people suffer influenza infection in Switzerland annually. Therefore, influenza epidemics are associated with substantial health-care costs, and considerable morbidity and mortality. At highest risk for adverse clinical outcomes are the young/elderly, and patients with chronic diseases or undergoing prolonged immunosuppression. Understanding the factors associated with transmission is a crucial element of improving current preventive strategies. The transmission events in the microenvironment of a population are highly complex. Influenza transmission is dependent on (a) ecological factors such as age distribution, density of schools, population density, and vaccine uptake rate; (b) viral factors such as strain characteristics and fitness; and (c) host factors such as the virus-induced immunity, which applies a potent selection pressure on viral replication. During influenza replication, the viral genome will acquire minor genetic alterations. Transmission of these strains drives continuous and rapid viral evolution in a community during each season. Nowadays, technologies allow rapid sequencing of the whole viral genome and determination of single nucleotide polymorphisms. This high-resolution analysis can be utilized to follow patient-to-patient transmission. For the influenza epidemics, the impact of factors (a-c) on transmission and viral genome evolution is not well described. Further, forecasting the evolution is difficult as illustrated by vaccines failing to protect against the predominant viral strains in circulation. Here, we propose a highly interdisciplinary analysis employing novel techniques from molecular epidemiology and geography with system biological tools that allow: (i) the exploration of the important drivers associated with influenza transmission, particularly with regard to age profiles and population density; and (ii) the analysis of the genetic evolution of circulating influenza lineages over time in selected areas of the city of Basel. We aim to devise novel algorithms capable of forecasting epidemic spread using real-time acquired data during a seasonal epidemic using insight obtained in (i) and (ii). This proposal builds upon the following key results of our work: (a) Comprehensive expertise in urban geography, (b) an extensive network for influenza diagnostics including “next generation sequencing” technologies, allowing the capture of influenza strains and analysis of isolates at a whole genome level; and (c) a recently developed temporal evolutionary model of influenza virus. The interdisciplinary project will expand on influenza data acquired from previous years, existing population data (e.g. population density), and established laboratory and computational techniques. We plan to acquire further epidemiological data (Urban Geography, University Basel). From prospective patient cohorts (University Hospital Basel, Paediatric University Hospital, and Centre of primary health care) we will conduct whole genome virus analysis using “next generation sequencing” (Clinical Microbiology, University Hospital Basel). We will develop a more complex computational model (BSSE, ETHZ) that describes the transmission of influenza considering system biological aspects at a broader sense, and quantify the parameters of that model using viral whole genome data.