Seasonal Allergic Rhinitis and Systems Biology-Oriented Biomarker Discovery

  • Erik W. Baars
  • Andreas F. M. Nierop
  • Huub F. J. Savelkoul
Reference work entry
Part of the Biomarkers in Disease: Methods, Discoveries and Applications book series


There is an increasing interest in science and medicine in the systems approach. Instead of the reductionist approach that focuses on the physical and chemical properties of the individual components, systems biology aims to describe, understand, and explain from the complex biological systems that are studied: all levels of structural and functional complexity, explicitly including the supracellular domain; their systems behavior or phenotypes; their networks with relationships that interact with the genome, the environment, and the phenotype; and their multifactorial processes involved in maintaining homeostasis and the breakdown of homeostasis within the system. This shift from a more reductionist to a more holistic approach on both the epistemological (theoretical) and the methodological level is also important for the conceptualization and the development of biomarkers.

Based on the dataset of a randomized controlled trial on the effects of a treatment of seasonal allergic rhinitis, using five different methods of permuted stepwise regression, three systems biology-oriented immunological pattern variables (biomarkers) were developed that demonstrated larger CV correct values than the separate cytokines with regard to the classification of cytokine samples in baseline (before treatment) and post-baseline (after treatment).

This example demonstrates that a systems biological approach in both the conceptualization and development of biomarkers is promising. However, more empirical studies with larger datasets are necessary to confirm the positive results of the presented study.


Biomarkers Cytokines Systems biology Permuted stepwise regression Seasonal allergic rhinitis 

List of Abbreviations






Cluster of Differentiation 4


A Rescaled Version of Lasso

CV Correct

Cross-Validated Correct Rate of Classification


Deoxyribonucleic Acid


Interferon Gamma






Least Absolute Shrinkage and Selection Operator




The Netherlands


Orthogonal Matching Pursuit


Peripheral Blood Mononuclear Cell Fraction

Phl p 1

Phleum Pretense


Permuted Stepwise Regression


R Squared


Radioallergosorbent Testing


Ribonucleic Acid


Seasonal Allergic Rhinitis


Forward Stepwise Selection


Stepwise Selection


Transforming Growth Factor Beta

Th Cells

T-Helper Cells


Tumor Necrosis Factor Alpha

Treg Cells

Regulatory T Cells





Parts of the text of this article concerning the development of the systems biological biomarkers are previously published in Baars et al. (2012).


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Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  • Erik W. Baars
    • 1
    • 2
  • Andreas F. M. Nierop
    • 3
  • Huub F. J. Savelkoul
    • 4
  1. 1.University of Applied Sciences LeidenLeidenThe Netherlands
  2. 2.Louis Bolk InstituteDriebergenThe Netherlands
  3. 3.MuvaraLeiderdorpThe Netherlands
  4. 4.Cell Biology and Immunology GroupWageningen UniversityWageningenThe Netherlands

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