Using Omics to Understand and Treat Pulmonary Vascular Disease

Abstract

Pulmonary arterial hypertension (PAH) is a devastating disease for which there is no cure. Presently this condition is differentiated from other diseases of the pulmonary vasculature by a practitioner's history, physical examination, and clinical studies with clinical markers of disease severity primarily guiding therapeutic choices. New technologies such as next generation DNA sequencing, high throughput RNA sequencing, metabolomics and proteomics have greatly enhanced the amount of data that can be studied efficiently in patients with PAH and other rare diseases. There is emerging data on the use of these "Omics" for pulmonary vascular disease classification and diagnosis and also new work that suggests molecular markers, including Omics, may be used to more efficiently match patients to their own most effective therapies. This review focuses on the state of knowledge on molecular classification and treatment of PAH. Strengths and weaknesses of current Omic technologies are discussed and how these new technologies can be used in the future to improve diagnosis of pulmonary vascular disease, more effectively treat patients with existing and future drugs, and generate new understanding of disease pathogenesis and mechanisms underlying treatment success or failure. Bioinformatic methods to analyze the large volumes of data are developing rapidly, but still present major challenges to interpretation of potential Omic findings in pulmonary vascular disease, with low numbers of patients studied and a potentially high false discovery rate. With more experience, precise and established drug response definitions, this field with move forward and will likely be a major component of the clinical care of PH patients in the future.

Keywords: OMICS data; omics-technologies; precision medicine; pulmonary hypertension; right ventricle.

Figure 1

(A) Histograms of survival in ongoing survivors (n = 25) vs. deceased patients (n = 14). Y axis depicts years since initiation of IV epoprostenol. Patients with good response may be considered those still alive after 8 years of drug or those who are deceased but after 8 years of IV epoprostenol therapy. Eight years is the median survival in our cohort (31). (B) Table showing proposed single or combined metrics of response to parenteral prostacyclin therapy.

Figure 2

Schematic of how Omic data could be used in a precision medicine trial of a drug in pulmonary arterial hypertension.