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APD, QT interval and Tx Values

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APD, QT interval and Tx Values

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Nombre: How to use.pdf
Tamaño: 202.0Kb
Formato: PDF
Descripción: 09/11/2017
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[Excel]
Nombre: APD.xlsx
Tamaño: 2.288Mb
Formato: Microsoft Excel 2007
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[Excel]
Nombre: QT.xlsx
Tamaño: 41.36Kb
Formato: Microsoft Excel 2007
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[Excel]
Nombre: Tx_APD.xlsx
Tamaño: 758.3Kb
Formato: Microsoft Excel 2007
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[Excel]
Nombre: Tx_QT.xlsx
Tamaño: 38.48Kb
Formato: Microsoft Excel 2007
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dc.contributor.author Saiz Rodríguez, Francisco Javier es_ES
dc.contributor.author Sanz i Carreras, Ferran es_ES
dc.contributor.author Pastor Maeso, Manuel es_ES
dc.contributor.author Trénor Gomis, Beatriz Ana es_ES
dc.contributor.author Gomis-Tena Dolz, Julio es_ES
dc.contributor.author Cano García, Jordi es_ES
dc.contributor.author Romero Pérez, Lucia es_ES
dc.date.accessioned 2017-10-31T09:03:33Z
dc.date.available 2017-10-31T09:03:33Z
dc.date.issued 2017-10-31T09:03:33Z
dc.identifier.uri http://hdl.handle.net/10251/90297
dc.description Every sheet in described files contains a table of numbers (doubles), resulting from the transformation of a three-dimensional matrix. To do so, the first two columns and the first row of each table contain the Coordinates x, y and z of the original matrix respectively (no units). They range from -3 to 1 for the x and y axis (first and second column) and from -3 to 0 for the z axis (first row). The nature of the remaining numbers differs between files: APD.xlsx contains the Action Potential Duration at 90% repolarization (APD90) values in milliseconds, QT.xlsx contains QT interval durations in milliseconds, Tx_APD.xlsx contains Tx values calculated from the tables in APD.xlsx and Tx_QT.xlsx contains Tx values calculated from the table in QT.xlsx. Coordinates were calculated as the logarithm of the ratio of a drug concentration (C) over the concentration that is required to inhibit a 50% of a given ion channel current (Half inhibitory concentration or IC50). They represent the block effect of such drug on three main currents which control the Action Potential shape and duration, namely, the rapid component of the potassium delayed rectifier current (IKr), the slow component of the potassium delayed rectifier current (IKs) and the calcium type L current (ICaL). The following formulae can be used to deduce mentioned Coordinates: x = log_10(C/(IC_50 (I_Kr))) ; y = log_10(C/(IC_50 (I_Ks ) )); z = log_10(C/(IC_50 (I_CaL))). These are indeed part of the Hill equation (Hill coefficient set to 1), where G is the channel’s resulting conductance and G0 is the channel’s control conductance: G_[x || y || z] = G_0·1/(1+C/(IC_(50, [x || y || z] ) )) = G_0·1/(1+10^([x || y || z]) ). Conductances of the three main currents are thus translated into cardiac cellular or tissue models to study the effect of a wide range of drug concentrations. The following parameters were obtained and summarized in currently described files. 1. APD90 values were obtained through simulation of the electrical activity of a single cardiac ventricular cell using the most up-to-date available model, the O’Hara Rudy Model (ORd) [1]. It can simulate the activity of three cell types, located in different layers of the human heart. Sheets included in APD.xlsx and Tx_APD.xlsx files (Endo, Mid and Epi) correspond to Endocardial, Mid-myocardial and Epicardial cells simulations using the respective Ord single cell models. 2. QT values were obtained through simulation of the activity of a cardiac transmural strand of 165 cells (60 Endo, 45 Mid and 60 Epi cells) as described in O’Hara et al. 2011 [1]. 3. Tx is a new index presented in Romero et al. 2017 [2] for assessing drug cardiac safety in the early stages of development. It was calculated as the ratio of a drug concentration that produced a 10% prolongation of the APD or QT intervals (D10) over the drug’s Effective Free Therapeutic Plasma Concentration (EFTPC), and thus has no units. Detailed methods of the performed simulations, as well as Tx calculation, can be consulted in [2]. es_ES
dc.description.abstract This repository contains four Excel 2017 files named “APD.xlsx”, “QT.xlsx”, “Tx_APD.xlsx” and “Tx_QT.xlsx”. APD.xlsx and Tx_APD.xlsx files contain three sheets (called “Epi”, “Mid” and “Endo”), whereas the rest contain only one sheet (called “QT”). These files contain the results of simulations performed in the O’Hara-Rudy model (ORd) [1] of human ventricular cells (206.766 simulations) and tissue (7072 simulations), which consist of APD90 and QT intervals as well as a new index called Tx extracted from both APD and QT values. References: [1]. O’Hara, T.; Virág, L.; Varró, A.; Rudy, Y. Simulation of the Undiseased Human Cardiac Ventricular Action Potential: Model Formulation and Experimental Validation. PLoS Comput. Biol. 2011, 7 (5), e1002061. [2]. Romero L., Cano J., Gomis-Tena J., Trenor B., Sanz F., Pastor M., Saiz J. In silico QT and APD Prolongation Assay for Early Screening of Drug-Induced Proarrhythmic Risk. Journal of Chemical Information and Modeling. 2017 (Currently in revision). es_ES
dc.language Inglés es_ES
dc.publisher Universitat Politècnica de València es_ES
dc.rights Reconocimiento - No comercial (by-nc) es_ES
dc.subject QT prolongation es_ES
dc.subject Drug-induced long-QT syndrome es_ES
dc.subject QT es_ES
dc.subject APD es_ES
dc.subject.classification MEDICINA es_ES
dc.subject.classification FARMACIA Y TECNOLOGIA FARMACEUTICA es_ES
dc.title APD, QT interval and Tx Values es_ES
dc.type Dataset es_ES
dc.identifier.doi 10.4995/Dataset/10251/90297 es_ES
dc.relation.projectID info:eu-repo/grantAgreement/MINECO//DPI2015-69125-R/ES/SIMULACION COMPUTACIONAL PARA LA PREDICCION PERSONALIZADA DE LOS EFECTOS DE LOS FARMACOS SOBRE LA ACTIVIDAD CARDIACA/ es_ES
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/115002/EU/Integrating bioinformatics and chemoinformatics approaches for the development of expert systems allowing the in silico prediction of toxicities/
dc.relation.projectID info:eu-repo/grantAgreement/GVA//PROMETEO%2F2016%2F088/ES/MODELOS COMPUTACIONALES PERSONALIZADOS MULTI-ESCALA PARA LA OPTIMIZACION DEL DIAGNOSTICO Y TRATAMIENTO DE ARRITMIAS CARDIACAS (PERSONALISED DIGITAL HEART)/ es_ES
dc.rights.accessRights Abierto es_ES
dc.contributor.affiliation Universitat Politècnica de València. Departamento de Ingeniería Electrónica - Departament d'Enginyeria Electrònica es_ES
dc.description.bibliographicCitation Saiz Rodríguez, FJ.; Sanz I Carreras, F.; Pastor Maeso, M.; Trénor Gomis, BA.; Gomis-Tena Dolz, J.; Cano García, J.; Romero Pérez, L. (2017). APD, QT interval and Tx Values. Universitat Politècnica de València. https://doi.org/10.4995/Dataset/10251/90297 es_ES
dc.type.version info:eu-repo/semantics/submittedVersion es_ES
dc.contributor.funder European Commission
dc.contributor.funder Generalitat Valenciana es_ES
dc.contributor.funder Ministerio de Economía y Competitividad es_ES


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