50 - OMICs in Stroke: Insight Into Stroke Through Epigenomics, Transcriptomics, Proteomics, Lipidomics, and Metabolomics

Abstract

OMICs-based technologies prove the opportunity to assess multiple nucleic acids, proteins, lipids, and metabolites associated with stroke. They could prove useful in understanding the pathophysiology of ischemic stroke (IS) and intracerebral hemorrhage (ICH) as well as potentially providing novel biomarkers for diagnosis, prognosis, treatment selection, cause of IS and ICH, and discovery of novel subgroups. In this chapter we review OMICs-based approaches in stroke including epigenomics, transcriptomics, proteomics, metabolomics, and lipidomics. Epigenetics is DNA methylation, histone modifications, transcription factors, microRNAs, and long intervening noncoding RNAs. Transcriptomics refers to the entire transcriptome of ∼20,000 genes which are alternatively spliced into ∼250,000 alternatively spliced, unique mRNA transcripts. RNAseq, arrays, and other technologies are used to study the transcriptome. Proteomics refers to all of the proteins found within a cell or biofluid (like serum or plasma), with >250,000 proteins from their mRNA transcripts. Mass spectrometry, antibody arrays, and other approaches are used to study the proteome. Metabolomics refers to the study of all metabolites in a cell or biological fluid, and similarly lipidomics is the study of all lipids in a cell or fluid. Nuclear magnetic resonance spectroscopy and mass spectrometry are used to study the metabolome and lipidome. To date, there are emerging studies providing proof of principle that OMICs approaches might eventually be used to diagnose and differentiate IS or ICH, identify the causes of IS and ICH, predict the cause of cryptogenic stroke, differentiate transient ischemic attacks (TIAs) from TIA mimics, predict patients likely to develop stroke, predict prognosis of IS and ICH, identify patients at greatest risk for hemorrhagic transformation, and potentially stratify patients for different types of treatments. While no OMICs-based test is currently used in practice, ongoing studies over the next decade will likely identify precision markers to aid clinicians in the diagnosis, treatment decisions, and risk classification of patients with stroke.