Linking childhood allergic asthma phenotypes with endotype through integrated systems biology: current evidence and research needs

Abstract

<jats:title>Abstract</jats:title> <jats:p>Asthma and other complex diseases results from a complex web of interactions involving inflammation, immunity, cell cycle, apoptosis, and metabolic perturbations across multiple organ systems. The extent to which various degrees of the age at onset, symptom severity, and the natural progression of the disease reflect multiple disease subtypes, influenced by unique process of development remains unknown. One of the most critical challenges to our understanding stems from incomplete understanding of the mechanisms. Within this review, we focus on the phenotypes of childhood allergic asthma as the basis to better understand the endotype for quantitative define subtypes of asthma. We highlight some of the known mechanistic pathways associated with the key hallmark events before the asthma onset. In particular, we examine how the recent advent of multiaxial -omics technologies and systems biology could help to clarify our current understanding of the pathway. We review how a large volume of molecular, genomic data generated by multiaxial technologies could be digested to identify cogent pathophysiologic molecular networks. We highlight some recent successes in application of these technologies within the context of other disease conditions for therapeutic interventions. We conclude by summarizing the research needs for the predictive value of preclinical biomarkers.</jats:p>

Impact Of “eHealth” in Allergic Diseases and Allergic Patients

“…In systems biology, large data sets collected by multiple modalities in populations, ideally with multiple dimensions of data for each individual, are used to generate networks that link phenotyping information to interdependent genetic, regulatory, metabolic, and environmental profiles. The resulting networks are used to predict behavior of the trait and generate novel, biologically relevant information [74].…”

Systems biology and in vitro validation identifies family with sequence similarity 129 member A (FAM129A) as an asthma steroid response modulator

“…Genomic systems biology approaches – defined as those that take a holistic approach to disease understanding informed by multiple disciplines, genomics, and bioinformatic data sources(13, 14) – have previously been effective at identifying biological processes contributing to the etiology of complex genetic diseases. (15, 16) Here, we take a systems approach to address the genomics of ICS response in individuals with asthma, building on our previous Bayesian-network based methodology, Reverse Engineering and Forward Simulation (REFS). (17) This method uses patient genomic and outcome data to identify genes driving the associations of interest, enriching for likely causal importance of such associations.…”

Perspectives in allergen immunotherapy: 2017 and beyond

“…In the last 2 years, several studies and reviews have sought to link allergic disease phenotypes and endotypes with potential targets for treatment in a precision medicine approach . In January 2017, the PRACTALL group published a summary on the potential for precision medicine in allergic disease, which concluded that while some progress has been made in defining endotypes for allergic disease and identifying biomarkers to guide a precision medicine approach to treatment, further validation and quantification of these biomarkers are needed to allow their translation into practice in the clinical management of allergic disease …”