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Computational Physiology and Biostatistics

This group is a subunit of the pediatric pulmonology research unit led by Prof. Urs Frey at the University Children's Hospital and the Clinical Morphology & Biomedical Engineering Department at University of Basel.

Our research activities are devoted to the analysis of pathyophysiological measurements, particularly those related to respiratory and cardiac function, using mathematical, computational, and statistical techniques. Of central interest to our group is the study of physiological and pathological reactions to environmental stimuli such as air pollution and exposure to tobacco smoke.

Our unit works in close collaboration with clinical researchers and epidemiologists. We use well established computational techniques to analyze clinical data. We also work on the efficient implementation of such techniques, and on the improvement and de novo development of computational methods.

Main current projects

Please note that not every project listed here was necessarily initiated by our group.

Patient phenotyping based on lung function fluctuation

Research questions/goals: Approaches to identifying phenotypes or endotypes in asthma have become increasingly relevant. However, in the majority of published approaches, the characterising parameters are only assessed at a single point in time, yielding phenotypes that might not remain stable as time progresses. We hypothesised that we could identify asthma and functional healthy phenotypes by investigating the patterns of fluctuation in airway function measured over a predetermined, sufficiently long time window of observation.

Current main results and/or publications: We have developed and applied a computational data-driven method that allows us to classify healthy individuals and different types of asthmatic patients according to the fluctuation patterns in their lung function. By applying this methodology to three different patient cohorts, we were able to validate our approach. Moreover, we found evidence for the existence of subtypes of asthma patients, who, if properly identified, would benefit from therapeutic strategies that differ from the commonly used anti-inflammatory treatment schemes. Check out our very recent paper: Functional phenotypes determined by fluctuation-based clustering of lung function measurements in healthy and asthmatic cohort participants.
Currently we are investigating in a cohort of adult asthma and COPD patients the mid-term temporal stability of the phenotype determined with our methodology.

Collaborators: Prof. Sven-Erik Dahlén and Dr. Maciej Kupczyk from the Experimental Asthma and Allergy Research Unit, The National Institute of Environmental Medicine, at Karolinska Institutet, Stockholm, Sweden. Prof. Erika von Mutzius, from the Dr. von Hauner Children's Hospital, Ludwig Maximilians University, Munich, Germany.

Assessing the effects of tobacco smoke and air pollution exposure on heart rate variability

Research questions/goals: In this project we aim to establish associations between air pollution and tobacco smoke exposure and changes in hear rate dynamics. To this end, we are using non-linear time series analysis methods to study interbeat interval time series from participants of the SAPALDIA cohort.

Current main results and/or publications: We have demonstrated a statistically significant association between tobacco smoke exposure and changes in heart rate variability, heart rate dynamics, and in the properties of the cardiovascular regulation. Moreover, we have explored the potential long term cardiovascular benefits of smoking cessation in former light and heavy smokers. We were honored with the "Best Paper of 2015" award by the scientific journal "Environmental research" for this work:

Long-term smoking cessation and heart rate dynamics in an aging healthy cohort: Is it possible to fully recover?

Funding: Tabakpräventionsfonds, Bundesamt für Gesundheit and Forschungsfond für Nachwuchsforschende der Universität Basel.

Collaborators: Prof. Nicole Probst-Hensch, Prof. Nino Künzli, Dr. Emmanuel Schaffner, and Dr. Martin Adam from the Swiss Tropical and Public Health Institute and the SAPALDIA team.

Understanding the molecular mechanisms of angiogenesis

Research questions/goals: In collaboration with scientists at University of Leeds (UK), we have developed an experimental platform that will help improve our understanding of the molecular mechanisms that govern angiogenesis, i.e. vessel growth in the human body, in both physiological and pathological (e.g. tumor induced) conditions. To this end, we have developed and validated an experimental approach that combines microfluidics technologies with fluorescence imaging, and spectral analysis.

Current main results and/or publications: Our measurements suggest that the macroscopic outcomes (e.g., cell proliferation, cell migration, and eventually angiogenesis) of exposing vascular endothelial cells to extracellular growth factors appear to be frequency modulated, i.e., the rate at which pulses of biochemical responses emerge within the cell, rather than the amplitude of these pulses, regulates and controls further cellular processes. This counterintuitive finding, if found to be also valid in a more physiological in vivo context, might challenge the conventional view of dose-response relationship that underlies traditional, and unfortunately poorly performing anti-angiogenic treatment approaches to cancer. A first publication is currently in preparation.

Collaborators: Dr. Sreenivasan Ponnambalam and Prof. Carmen Molina-Paris,University of Leeds, UK.

Image of a human umbilical vein endothelial cell (HUVEC) obtained using fluorescence confocal microscopy. Within our project, we record and analyze the emission spectrum in such images in order to obtain real-time information about pathway activity upon stimulation with extracellular growth factors.

Mathematical modeling and computer simulation of host-pathogen interactions

Research questions/goals: Currently, our focus is to elucidate the mechanisms that allow for persistent Epstein-Barr virus (EBV) infection in humans using mathematical modeling and computer simulation.

Current main results and/or publications: Hawkins JB, Delgado-Eckert E, Thorley-Lawson DA, Shapiro M. The cycle of EBV infection explains persistence, the sizes of the infected cell populations and which come under CTL regulation. PLoS Pathogens. 2013 Oct;9(10):e1003685. doi:10.1371/journal.ppat.1003685.
If you are interested in this topic, please watch the following video of a talk I gave at the 3rd Workshop and Conference on "Modeling Infectious Diseases" organized by The Indian Institute of Mathematical Sciences (IMSc), Chennai, India, November 2015.

Funding: New collaborations and facets of this research line were funded by a Marie Curie International Research Staff Exchange Scheme grant from the European Union, which started on May 2013.

Collaborators: Dr. Michael Shapiro, Prof. David Thorley-Lawson at Tufts Medical School, Tufts University, Boston, and Dr. Jared Hawkins at the Laboratory for Personalized Medicine at Harvard Medical School, Boston

Biological model of EBV infection in humans

Many years of scientific research have led our collaborators to propose a cycle of replication for the Epstein-Barr virus (EBV) in the human body. Indeed, experimental evidence suggests that the virus takes advantage of the physiological cycle of B cells. We have tested some of the logical consequences of this model using mathematical modelling and computer simulation. We were able to derive consequences concerning the differences in the pathology of EBV infection between individuals in a population of EBV positive persons. It turns out that the differences predicted by the model are actually observed in the human population! This is a strong argument in favor of the validity of the “cyclic pathogen model” of EBV infection. Find out more.

Assessment of body temperature control in preterm infants

Research questions/goals: In this project we are looking at time series of body temperature measurements in infants to learn more about the relationship between physiological development and temperature regulation mechanisms.

Current main results and/or publications: We finished recruiting participants, and a large amount of measurements have been successfully completed. The collected time series of body temperature measurements have been analyzed. Furthermore, we have found associations between some of the time-series analysis parameters and clinical, particularly developmental, magnitudes. The results of this analysis have been recently published.

Currently, we are analyzing this data set from a control theoretical point of view.

Collaborators: Prof. Sven Schulzke, Dr. med. Isabelle Pramana, and Dr. Kerstin Jost, from UKBB.

Spatio-temporal model of NO2 pollution levels in the Canton Bern and in the city of Bern

Research questions/goals: Many epidemiological studies require the assessment of the participants’ individual air pollution exposure during periods of weeks or months (e.g. during pregnancy). In this project we aimed at developing a model capable of making NO2 air concentration predictions in the city and canton of Bern, Switzerland, as a function of geographic coordinates, time of the year, and other variables. Our model was trained using NO2 measurements from a countryside fixed air quality monitoring station, length of major roads and population density, traffic load, distance to the nearest major road, industrial land use, temperature, and boundary layer height, among others.

Current main results and/or publications: We have constructed a final model after a variable selection process. The model has been trained and validated with an external data set. Read more in our recent article: Air pollution modelling for birth cohorts: a time-space regression model.

Collaborators: Dr. Elena Proietti; Dr. Danielle Vienneau and Prof. Martin Röösli from the Swiss Tropical and Public Health Institute.

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