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The absorption, distribution and excretion of drugs are largely determined by their transporters (DTs), the variability of which has thus attracted considerable attention. There are three aspects of variability: epigenetic regulation and genetic polymorphism, species/tissue/disease-specific DT abundances, and exogenous factors modulating DT activity. The variability data of each aspect are essential for clinical study, and a collective consideration among multiple aspects becomes crucial in precision medicine. However, no database is constructed to provide the comprehensive data of all aspects of DT variability.
Herein, the Variability of Drug Transporter Database (VARIDT) was introduced to provide such data. First, 177 and 146 DTs were confirmed, for the first time, by the transporting drugs approved and in clinical/preclinical, respectively. Second, for the confirmed DTs, VARIDT comprehensively collected all aspects of their variability (23 947 DNA methylations, 7317 noncoding RNA/histone regulations, 1278 genetic polymorphisms, differential abundance profiles of 257 DTs in 21 781 patients/healthy individuals, expression of 245 DTs in 67 tissues of human/model organism, 1225 exogenous factors altering the activity of 148 DTs), which allowed mutual connection between any aspects. Due to huge amount of accumulated data, VARIDT made it possible to generalize characteristics to reveal disease etiology and optimize clinical treatment.
Multiple aspects and sub-aspects of variability described in VARIDT. ERGPDT (red): epigenetic regulations and genetic polymorphisms of DT; DSTSPA (dark blue): disease-, species- and tissue-specific protein abundance of DT; EFMDTA (gray): exogenous factors modulating DT activity. The leaf of the corresponding sub-aspect indicated its typical/potential application.
Yin J, Sun W, Li F, et al. VARIDT 1.0: variability of drug transporter database [published correction appears in Nucleic Acids Res. 2020 Jan 8;48(D1):D1171]. Nucleic Acids Res. 2020;48(D1):D1042-D1050. doi:10.1093/nar/gkz779
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