Resolving Clinical Phenotypes into Endotypes in Allergy: Molecular and Omics Approaches

Mersha, Tesfaye B.; Afanador, Yashira; Johansson, Erika; Proper, Steven P.; Bernstein, Jonathan A.; Rothenberg, Marc E.; Hershey, Gurjit K. Khurana

doi:10.1007/s12016-020-08787-5

Cited by 25 publications

(14 citation statements)

References 209 publications

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“…Therefore, to achieve multi-omics integration and application to precision medicine asthma, it is important to address the current challenges by establishing a solid evidence base. This can be accomplished through more rigorous study designs, integration of high-dimensional data from various sources, development of computational approaches for large amounts of data, and a reduction in cost of omics analyses [206].…”

Section: Integrating Omics In Asthmamentioning

confidence: 99%

Multi-Omics Profiling Approach to Asthma: An Evolving Paradigm

Gautam

Johansson

Mersha

2022

JPM

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Asthma is a complex multifactorial and heterogeneous respiratory disease. Although genetics is a strong risk factor of asthma, external and internal exposures and their interactions with genetic factors also play important roles in the pathophysiology of asthma. Over the past decades, the application of high-throughput omics approaches has emerged and been applied to the field of asthma research for screening biomarkers such as genes, transcript, proteins, and metabolites in an unbiased fashion. Leveraging large-scale studies representative of diverse population-based omics data and integrating with clinical data has led to better profiling of asthma risk. Yet, to date, no omic-driven endotypes have been translated into clinical practice and management of asthma. In this article, we provide an overview of the current status of omics studies of asthma, namely, genomics, transcriptomics, epigenomics, proteomics, exposomics, and metabolomics. The current development of the multi-omics integrations of asthma is also briefly discussed. Biomarker discovery following multi-omics profiling could be challenging but useful for better disease phenotyping and endotyping that can translate into advances in asthma management and clinical care, ultimately leading to successful precision medicine approaches.

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Section: Integrating Omics In Asthmamentioning

confidence: 99%

Multi-Omics Profiling Approach to Asthma: An Evolving Paradigm

Gautam

Johansson

Mersha

2022

JPM

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“…While allergists have for several decades participated in the precision afforded by personalized allergen immunotherapy for allergic rhinitis and conjunctivitis (allergy shots), it was not until relatively recently that biologics offered more specific treatment options for other allergic diseases. The use of anti-interleukin (IL)-5 agents in asthma is an illustrative example of the power and simultaneous challenge of precision medicine in allergy (15). When anti-IL-5 antibodies were first tested in mild or moderate severity asthmatics, they failed to show clinical benefit despite reductions in eosinophils (16,17); however, when studies were limited to steroid-dependent asthmatics with persistently elevated eosinophil counts, it performed well with significant steroid-sparing effect leading to the first new class of asthma medications in 12 years (18,19).…”

Section: Precision Treatment In Allergymentioning

confidence: 99%

Achieving Precision Medicine in Allergic Disease: Progress and Challenges

2021

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Allergic diseases (atopic dermatitis, food allergy, eosinophilic esophagitis, asthma and allergic rhinitis), perhaps more than many other traditionally grouped disorders, share several overlapping inflammatory pathways and risk factors, though we are still beginning to understand how the relevant patient and environmental factors uniquely shape each disease. Precision medicine is the concept of applying multiple levels of patient-specific data to tailor diagnoses and available treatments to the individual; ideally, a patient receives the right intervention at the right time, in order to maximize effectiveness but minimize morbidity, mortality and cost. While precision medicine in allergy is in its infancy, the recent success of biologics, development of tools focused on large data set integration and improved sampling methods are encouraging and demonstrates the utility of refining our understanding of allergic endotypes to improve therapies. Some of the biggest challenges to achieving precision medicine in allergy are characterizing allergic endotypes, understanding allergic multimorbidity relationships, contextualizing the impact of environmental exposures (the “exposome”) and ancestry/genetic risks, achieving actionable multi-omics integration, and using this information to develop adequately powered patient cohorts and refined clinical trials. In this paper, we highlight several recently developed tools and methods showing promise to realize the aspirational potential of precision medicine in allergic disease. We also outline current challenges, including exposome sampling and building the “knowledge network” with multi-omics integration.

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“…The intelligent integration of 'omics' data with detailed clinical, environmental and lifestyle information has the potential to identify the molecular identity and subclasses of the underlying disease aetiologies. 25,26 Yet generating,…”

Section: Atopic Dermatitis and Psoriasis Are The Most Common Chronic Inflammatory Skin Diseasesmentioning

confidence: 99%