Title:Phenomics of Vascular Disease: The Systematic Approach to the Combination Therapy
VOLUME: 13 ISSUE: 4
Author(s):Yeshan Han, L i Li, Yaping Zhang, Hong Yuan, Linda Ye, Jianzhong Zhao and Dayue Darrel Duan
Affiliation:Laboratory of Cardiovascular Phenomics, Department of Pharmacology, University of Nevada School of Medicine, Center for Molecular Medicine 303F, 1664 N Virginia Street/MS 318, Reno, Nevada 89557-0318, USA.
Keywords:Vascular disease, phenomics, hypertension, stroke, combination therapy.
Abstract:Vascular diseases are usually caused by multifactorial pathogeneses involving genetic and
environmental factors. Our current understanding of vascular disease is, however, based on the focused
genotype/phenotype studies driven by the “one-gene/one-phenotype” hypothesis. Drugs with “pure
target” at individual molecules involved in the pathophysiological pathways are the mainstream of current
clinical treatments and the basis of combination therapy of vascular diseases. Recently, the combination of genomics,
proteomics, and metabolomics has unraveled the etiology and pathophysiology of vascular disease in a big-data fashion
and also revealed unmatched relationships between the omic variability and the much narrower definition of various clinical
phenotypes of vascular disease in individual patients. Here, we introduce the phenomics strategy that will change the
conventional focused phenotype/genotype/genome study to a new systematic phenome/genome/proteome approach to the
understanding of pathophysiology and combination therapy of vascular disease. A phenome is the sum total of an organism’s
phenotypic traits that signify the expression of genome and specific environmental influence. Phenomics is the
study of phenome to quantitatively correlate complex traits to variability not only in genome, but also in transcriptome,
proteome, metabolome, interactome, and environmental factors by exploring the systems biology that links the genomic
and phenomic spaces. The application of phenomics and the phenome-wide associated study (PheWAS) will not only
identify a systemically-integrated set of biomarkers for diagnosis and prognosis of vascular disease but also provide novel
treatment targets for combination therapy and thus make a revolutionary paradigm shift in the clinical treatment of these
devastating diseases.
