VARIDT 1.0: variability of drug transporter database

Abstract

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, and is freely accessible at: https://db.idrblab.org/varidt/ and http://varidt.idrblab.net/.

Drosophila SLC22 Orthologs Related to OATs, OCTs, and OCTNs Regulate Development and Responsiveness to Oxidative Stress

“…Out of the seven transporters chosen by the International Transporter Consortium and the FDA for evaluation during drug development, three (OAT1, OAT3, and OCT2) are members of the SLC22 family [49]. 17 SLC22 members are also identified as drug transporters by the VARIDT database [50]. In addition to their pharmacological importance, many of these transporters transport metabolites that play a role in the response to endogenous stressors such as oxidative stress induced by reactive oxygen species.…”

Are in vitro and in silico approaches used appropriately for animal-based major depressive disorder research?

“…Nowadays there is an increasing number of databases on human and animal protein expression differences (for a review see [12]) which, on the one hand, makes it easier for researchers to locate and cite existing data; but, on the other hand, might stimulate animal research to be conducted independently of in vitro and in silico data to populate such databases.…”

RF-PseU: A Random Forest Predictor for RNA Pseudouridine Sites

“…As an alternative to costly and labor-intensive laboratory experiments, robust, swift, and inexpensive computational methods for RNA chemical modification prediction have emerged recently, owing to the increasing amount of data generated in this post-genomics era (Libbrecht and Noble, 2015). A large number of m6A (Chen et al, 2015(Chen et al, , 2018a(Chen et al, ,b, 2019aZhou et al, 2016;Zhao et al, 2019;Zou et al, 2019) and m5C (Feng et al, 2016;Qiu et al, 2017;Li et al, 2018;Sabooh et al, 2018;Zhang et al, 2018;Yin et al, 2019) site predictors based on traditional machine learning and emerging deep learning algorithms have been proposed. However, few computational tools have been developed to predict pseudouridine sites.…”