Toward Composite Molecular Signatures in the Phenotyping of Asthma

Abstract

The complex biology of respiratory diseases such as asthma is feeding the discovery of various disease phenotypes. Although the clinical management of asthma phenotypes by using a single biomarker (e.g., sputum eosinophils) is successful, emerging evidence shows the requirement of multiscale, high-dimensional biological and clinical measurements to capture the complexity of various asthma phenotypes. High-throughput "omics" technologies, including transcriptomics, proteomics, lipidomics, and metabolomics, are increasingly standardized for biomarker discovery in asthma. The leading principle is obeying available guidelines on omics analysis, thereby strictly limiting false discovery. In this review we address the concept of transcriptomics using microarrays or next-generation RNA sequencing and their applications in asthma, highlighting the strengths and limitations of both techniques, and review metabolomics in exhaled air (breathomics) as a noninvasive alternative for sampling the airways directly. These developments will inevitably lead to the integration of molecular signatures in the phenotyping of asthma and other diseases.

A European Respiratory Society technical standard: exhaled biomarkers in lung disease

“…Molecular analysis of exhaled breath volatiles (breathomics) provides a noninvasive tool for exploring the human body, including the lung and other organs [85][86][87][88][89]. High-throughput omics technologies based on unbiased systems biology approaches, including transcriptomics, proteomics, lipidomics and metabolomics, are increasingly used for phenotype discovery and have potential as "point-of-care" diagnostic tools [90][91][92][93][94][95][96].…”

Mast cells in asthma: biomarker and therapeutic target

“…The molecular analysis of highly characterised cohorts of asthma patients should help to identify biomarkers of asthma subtypes, which might lead to more efficient and personalised therapies for asthma [1,2]. So far, asthma has been mainly divided into two subtypes: T-helper cell type 2 (Th2)-high asthma, which comprises patients with airway and systemic eosinophilia who are responsive to glucocorticoids; and Th2-low asthma, which comprises patients without airway or systemic eosinophilia who are not responsive to glucocorticoids [3].…”

Non-invasive Biomarkers in Asthma: Promises and Pitfalls

“…There are several different triggers in asthma, with various pathophysiological pathways in parallel resulting in clinical expression that may be rather similar. Therefore, repeated multiscale, multidimensional measurements may be needed to capture this complexity, which may yield more useful information than single or even panels of combined biomarkers [60]. In this view, molecular composite signatures may be obtained by highthroughput "omics" technologies, which are increasingly standardised.…”

“…In this view, molecular composite signatures may be obtained by highthroughput "omics" technologies, which are increasingly standardised. Several large-scale studies of the genome, transcriptome, proteome or metabolome have produced an enormous amount of data and it is pivotal to follow the available guidelines in order to avoid false discoveries [60]. The composite high-dimensional signatures or fingerprints are based on pattern recognition underlying complex non-linear biology systems.…”