Présentation PosterInternational audienc

Bastogne, Thierry

Batista, Levy

Beckler, Matthias

Doerr, Leo

Fertig, Niels

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HAL Id: hal-01669436https://hal.archives-ouvertes.fr/hal-01669436Submitted on 20 Dec 2017HAL is a multi-disciplinary open accessarchive for the deposit and dissemination of sci-entific research documents, whether they are pub-lished or not. The documents may come fromteaching and research institutions in France orabroad, or from public or private research centers.L’archive ouverte pluridisciplinaire HAL, estdestinée au dépôt et à la diffusion de documentsscientifiques de niveau recherche, publiés ou non,émanant des établissements d’enseignement et derecherche français ou étrangers, des laboratoirespublics ou privés.Coupled impedance & field potential data analysis of invitro cardiomyocyte assaysLevy Batista, Leo Doerr, Matthias Beckler, Niels Fertig, Thierry BastogneTo cite this version:Levy Batista, Leo Doerr, Matthias Beckler, Niels Fertig, Thierry Bastogne. Coupled impedance & fieldpotential data analysis of in vitro cardiomyocyte assays. Safety Pharmacology Society 2017 AnnualMeeting, SPS 2017, Sep 2017, Berlin, Germany. ￿hal-01669436￿Coupled Impedance & Field Potential Data Analysis of in vitro Cardiomyocyte Assays L. BATISTA1,2,3, L. DOERR4, M. BECKLER4, N. FERTIG4, T. BASTOGNE1,2,3 1CRAN, 2INRIA BIGS, 3CYBERnano, 4NANION Background. One goal of the Comprehensive in vitro ProArrhythmia Assay  initiative is to predict more accurately potentially torsadogenic compounds in an earlier stage of drug development. To that aim one of the CiPA component is to assess capabilities of label-free in vitro assays (impedance and extracellular field potential signals) applied to human stem cell-derived cardiomyocytes.Impedance and extracellular field potential signals belong to the class of high-content data for which the most challenging issue to be addressed is to identify predictive biomarkers of cardiotoxicity in a large amount of data. To that aim, new statistical signal-processing methods are needed and the objective of this study is to develop a non-supervized technique able to rank the contractility and electrophysiological effects of tested compounds.Fig.4: Estimation of the EC50 profiles. Left: Flat model meaning no effect. Right: EC50 values estimation based on the Hill’s modelResultsResults have emphasized some correlations but also some differences between the cardio-effects detected between the two types of signals. For the first tested compound, the absence of effects is detected by the two measurements. For the second compound, effects are detected but the modified characteristics are different in impedance and field potential signals.ConclusionThe proposed computation method automates the combined analysis of impedance and extracellular field potential measurements on cardiomyocytes. Complementary effects have been detected by the data analysis for the impedance and field potential signals. This comparative study will be soon extended to a larger batch of molecules for validationFig.3: Scores calculated on all indicators. Left: No statistically significant effect. Right: A dose-response information appears but on different indicators between IMP and EFPFig.2: Characterization of each sweep with 5 indicators (IMP) among the time (4 indicators for EFP)Fig.1: Two types of signals Top : Impedance (IMP). Bottom: Extracellular field potential (EFP)ObjectivesThe CardioExcyte 96 (Nanion Technologies Gmbh) is used to measure both impedance and extracellular field potential signals on two CiPA compounds applied to cardiomyocytes. The developed method for data processing firstly computes nine numerical indicators. They characterize the time variations of frequency, amplitude, shape and irregularity of cell impedance and field potential signals. The ninth parameter is the cardiomyocyte viability index. In a second phase, statistical tests are applied on each characteristics to evaluate the concentration effect of the tested compounds. Finally, results of the previous statistical results are aggregated in a cardio-effect score, graduated from 0 (no influence) to 18 (highly disturbed beating). This innovative approach was tested using in vitro data obtained from two molecules (1 cardiotoxic and 1 non-cardiotoxic compounds).MethodsAnnual Meeting of Safety Pharmacology Society, Berlin, 24-27 Sep. 201710-9 10-8 10-7 10-6 10-5 10-4 10-3 10-2 10-1Concentration012345678910Score29A03 A EC50A=1.5e-05A EC 50R=1.6e-05DataModel AModel R10-9 10-8 10-7 10-6 10-5 10-4 10-3 10-2 10-1Concentration012345678910Score29A01DataConstant Model 1u  3u 10u 30u012345678910Scores 29A03 (P-Value=0.01) IMPT F A I S 1u  3u 10u 30u012345678910Scores 29A03 (P-Value=0.01) EFPF A I S 1u  3u 10u 30u-1012345678910Scores 29A01 (P-Value=0.01) IMPT F A I S 1u  3u 10u 30u-1012345678910Scores 29A01 (P-Value=0.01) EFPF A I SF: Frequency (bpm) A: Peak-to-Peak Amplitude S: Beating Shape T: Cell Impedance Trend I: Beating IrregularityWell A1 - IMP - At 6h30Well A1 - EFP - At 6h30

Coupled impedance & field potential data analysis of in vitro cardiomyocyte assays

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Coupled impedance & field potential data analysis of in vitro cardiomyocyte assays

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