Abstract
A pharmacogenomics-based pathway represents a series of reactions that occur between drugs and genes in the human body after drug administration. PG-path is a pharmacogenomics-based pathway that standardizes and visualizes the components (nodes) and actions (edges) involved in pharmacokinetic and pharmacodynamic processes. It provides an intuitive understanding of the drug response in the human body. A pharmacokinetic pathway visualizes the absorption, distribution, metabolism, and excretion (ADME) at the systemic level, and a pharmacodynamic pathway shows the action of the drug in the target cell at the cellular-molecular level. The genes in the pathway are displayed in locations similar to those inside the body. PG-path allows personalized pathways to be created by annotating each gene with the overall impact degree of deleterious variants in the gene. These personalized pathways play a role in assisting tailored individual prescriptions by predicting changes in the drug concentration in the plasma. PG-path also supports counseling for personalized drug therapy by providing visualization and documentation.
Highlights
Background frame and imageIn a PK pathway, a background frame modeled on the human body is utilized so that the proteins can be superimposed on the correct human compartments
Each pathway is produced by dividing the PK pathway, representing the ADME in the human body, and the PD pathway, describing the action of the drug at the target cell
PK pathways have been elucidated at the systemic level based on metabolism and transport, and PD pathways have been characterized at the cellular and molecular- level based on drug actions and responses
Summary
In a PK pathway, a background frame modeled on the human body is utilized so that the proteins can be superimposed on the correct human compartments. A comprehensive range of standard background compartments was selected to precisely express the ADME routes. In the standard PK pathway frame, the background anatomical organs are the eye, nose, mouth, brain, lung, heart, muscle, kidney, liver, adrenal gland, testis, intestines, placenta, and skin, in addition to other compartments that are needed for a few drugs. The routes of administration include eye drops, inhalation, sublingual and buccal absorption, oral ingestion, intravenous injection, intramuscular injection, and percutaneous absorption. (S1A and S1B Fig) We drew one background image, composed of standardized body compartments, to graphically visualize the ADME of the drug in the PK pathway. The tissues site at which metabolism or transport occurs depends on the expression levels of enzymes and transporters, which can be found by referring to the Protein Atlas databases. (S1A and S1B Fig) We drew one background image, composed of standardized body compartments, to graphically visualize the ADME of the drug in the PK pathway. (Table 1, S1C and S1D Fig)
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