Systems biology of asthma and allergic diseases: a multiscale approach

Abstract

Systems biology is an approach to understanding living systems that focuses on modeling diverse types of high-dimensional interactions to develop a more comprehensive understanding of complex phenotypes manifested by the system. High-throughput molecular, cellular, and physiologic profiling of populations is coupled with bioinformatic and computational techniques to identify new functional roles for genes, regulatory elements, and metabolites in the context of the molecular networks that define biological processes associated with system physiology. Given the complexity and heterogeneity of asthma and allergic diseases, a systems biology approach is attractive, as it has the potential to model the myriad connections and interdependencies between genetic predisposition, environmental perturbations, regulatory intermediaries, and molecular sequelae that ultimately lead to diverse disease phenotypes and treatment responses across individuals. The increasing availability of high-throughput technologies has enabled system-wide profiling of the genome, transcriptome, epigenome, microbiome, and metabolome, providing fodder for systems biology approaches to examine asthma and allergy at a more holistic level. In this article we review the technologies and approaches for system-wide profiling, as well as their more recent applications to asthma and allergy. We discuss approaches for integrating multiscale data through network analyses and provide perspective on how individually captured health profiles will contribute to more accurate systems biology views of asthma and allergy.

Keywords: Systems biology; allergy; asthma; atopic; big data; epigenome; genome; individual health profile; metabolome; microbiome; network; transcriptome.

Figure 1. Relationship between system-wide profiles in asthma and allergy

Data on the genome, transcriptome, epigenome, microbiome, and metabolome in asthma and allergy have been generated. These types of data are interdependent and interact. Systems biology approaches can be used to model the multidimensional interactions that characterize complex disease.

Figure 2. Moving toward a systems biology view of asthma and allergic diseases

The colored circular nodes represent genetic, regulatory, metabolite, and environmental entities associated with asthma and allergic disorders. Their identification and potential connectivity can be assessed by the profiling represented in the large rectangular nodes. Green rectangular nodes represent diseases of interest. Orange lines (edges) denote evidence for associations between the implicated nodes in asthma and allergy, many of which are reviewed in this article. Dashed blue edges denote relationships that are currently less well-studied. Examination of the network’s collective nodes and edges, or a substantial subset thereof, would move us toward a systems biology understanding of asthma and allergy.

Figure 3. Personal health profiles captured by individuals themselves will add the next big data dimension to understanding asthma and allergic diseases

Data that individuals gather passively through wearable devices and mobile apps for personal health will enable deeper phenotyping and real-time profiling of environmental exposures. Combined with continued advances in system-wide profiling, network models of asthma and allergic disease will become more accurate for disease prediction and therapeutics.