LAUSR

Graphical AbstractMoving from the genome to the transcriptome to the proteome reveals increasing biological complexity for understanding pathways of atherosclerotic disease and its progression. The process of gene expression in which coding DNA strands are transcribed into mRNA and translated into specific proteins are only the first steps in understanding the increasingly complex biological interactions that subsequently occur within proteins (which include post-translational modifications such as phosphorylation, acetylation, glycosylation, and methylation) as well as between proteins (such as protein–protein network interactions). In turn, proteins have diverse impacts on cell, tissue, organ, and organism structures and functions, including between cell signalling, control of metabolism, and regulation of growth and senescence. Unlike genetic data and associated polygenic risk scores (which are inherently static), protein data and associated protein-based risk scores are dynamic and responsive to a wide variety of environmental and behavioural stimuli including, as examples, lifestyle change, exercise, and nutrition. As such, moving from a genomics focus to a proteomics focus may provide therapeutic insights not only for late-stage drug development (secondary prevention, modestly modifiable) but also for early-stage primordial and primary prevention (highly and moderately modifiable).