Pharmacological dataset on drug-induced TdP risk assessment

A manually collected dataset that investigates the proarrhythmic risk of 109 drugs using parameters obtained from biophysical models. The dataset defines 4 torsade de pointes (TdP) risk categories in the parameter “class”. For each of 109 drugs, IC50 values and Hill coefficients (h) for INa, INaL, IKr, Ito, ICaL, IK1, and IKs and human effective free therapeutic plasma concentration (EFTPC) were obtained (see [1]). Detailed description follows. A dash in the dataset means that no value was found publicly available, thus it was considered that the drug effect on that current was negligible. The dataset can be used (and is important) while studing causal discovery methods to infer ion channels selection for the drug-induced TdP risk Size of dataset: 109 Number of features: 16 Ground truth: No Type of graph: to be estimated Features: Class - class of the drug according to the torsade de pointes (TdP) is a life-threatening arrhythmia characterised by a gradual change in the amplitude and twisting of the QRS complexes. Class 1 (known risk of TdP), class 2 (possible risk of TdP), class 3 (conditional risk of TdP), class 4 (drugs with a lack of evidence of TdP). EFTPC —effective free therapeutic plasma concentration, defined as the drug concentration in the plasma required to produce the desired therapeutic effect in the body. IC50- value that represents the minimal concentration of a drug that is required for 50% inhibition in vitrovalues (given in nm). hIKr, hINa,hINaL, hICaL, hIKs, hIK1, hIto - Hill coefficients of the currents. See more information in the file medications_description.html. See more information to run in R environment in the file medications_description.Rmd References: [1] Llopis-Lorente, Jordi and Gomis-Tena, Julio and Cano, Jordi and Romero, Lucía and Saiz, Javier and Trenor, Beatriz. InSilico Classifiers for the Assessment of Drug Proarrhythmicity. Journal of Chemical Information and Modeling, 2020, 60(10), 5172--5187 [2] Al-Ali,Safaa and Llopis-Lorente, Jordi and Mora, Maria Teresa and Sermesant, Maxime and Trénor, Beatriz and Balelli, Irene. A causal discovery approach for streamline ion channels selection to improve drug-induced TdP risk assessment. 2023.hal-04105144本数据集为人工采集所得，旨在基于生物物理模型获取的参数，探究109种药物的致心律失常风险。本数据集在「class」参数中定义了4种尖端扭转型室性心动过速（torsade de pointes, TdP）风险等级。 针对全部109种药物，本数据集采集了其针对INa、INaL、IKr、Ito、ICaL、IK1、IKs这7种离子通道的半数抑制浓度（IC50）与希尔系数（Hill coefficient，记为h），以及人体有效游离治疗血浆浓度（effective free therapeutic plasma concentration, EFTPC）相关数据（详见参考文献[1]）。下文将提供详细说明。 数据集中的短横线表示未查询到公开可用的对应数值，因此认为该药物对对应离子电流的影响可忽略不计。本数据集在研究用于推断药物诱导TdP风险相关离子通道选择的因果发现方法时具有重要应用价值。 数据集基本信息如下： - 样本量：109 - 特征数：16 - 真实标签：无 - 图结构类型：待估计 - 特征说明： 1. Class（药物风险类别）：基于尖端扭转型室性心动过速（TdP）风险划分的药物等级。TdP是一种以QRS波群振幅逐渐变化、形态扭转为特征的致命性心律失常。具体等级如下： - 1级：明确存在TdP风险 - 2级：可能存在TdP风险 - 3级：条件性TdP风险 - 4级：无TdP相关证据的药物 2. EFTPC（有效游离治疗血浆浓度）：指在人体内产生预期治疗效果所需的血浆药物浓度。 3. IC50（半数抑制浓度）：指体外实验中实现50%抑制所需的最低药物浓度，单位为纳摩尔（nm）。 4. hIKr、hINa、hINaL、hICaL、hIKs、hIK1、hIto：对应离子电流的希尔系数。 更多详情请参阅medications_description.html文件；关于R环境下的运行说明，请参阅medications_description.Rmd文件。 参考文献： [1] Llopis-Lorente, Jordi、Gomis-Tena, Julio、Cano, Jordi、Romero, Lucía、Saiz, Javier、Trenor, Beatriz. 用于药物致心律失常风险评估的硅基分类器. 化学信息与建模杂志, 2020, 60(10): 5172–5187 [2] Al-Ali, Safaa、Llopis-Lorente, Jordi、Mora, Maria Teresa、Sermesant, Maxime、Trénor, Beatriz、Balelli, Irene. 一种用于简化离子通道选择以改进药物诱导TdP风险评估的因果发现方法. 2023, hal-04105144