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Novel Analysis Software for Detecting and Classifying Ca2+ Transient Abnormalities in Stem Cell-Derived Cardiomyocytes
Comprehensive functioning of Ca2+ cycling is crucial for excitation-contraction coupling of cardiomyocytes (CMs). Abnormal Ca2+ cycling is linked to arrhythmogenesis, which is associated with cardiac disorders and heart failure. Accordingly, we have generated spontaneously beating CMs from induced p...
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Published in: | PloS one 2015-08, Vol.10 (8), p.e0135806-e0135806 |
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description | Comprehensive functioning of Ca2+ cycling is crucial for excitation-contraction coupling of cardiomyocytes (CMs). Abnormal Ca2+ cycling is linked to arrhythmogenesis, which is associated with cardiac disorders and heart failure. Accordingly, we have generated spontaneously beating CMs from induced pluripotent stem cells (iPSC) derived from patients with catecholaminergic polymorphic ventricular tachycardia (CPVT), which is an inherited and severe cardiac disease. Ca2+ cycling studies have revealed substantial abnormalities in these CMs. Ca2+ transient analysis performed manually lacks accepted analysis criteria, and has both low throughput and high variability. To overcome these issues, we have developed a software tool, AnomalyExplorer based on interactive visualization, to assist in the classification of Ca2+ transient patterns detected in CMs. Here, we demonstrate the usability and capability of the software, and we also compare the analysis efficiency to manual analysis. We show that AnomalyExplorer is suitable for detecting normal and abnormal Ca2+ transients; furthermore, this method provides more defined and consistent information regarding the Ca2+ abnormality patterns and cell line specific differences when compared to manual analysis. This tool will facilitate and speed up the analysis of CM Ca2+ transients, making it both more accurate and user-independent. AnomalyExplorer can be exploited in Ca2+ cycling analysis to study basic disease pathology and the effects of different drugs. |
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Abnormal Ca2+ cycling is linked to arrhythmogenesis, which is associated with cardiac disorders and heart failure. Accordingly, we have generated spontaneously beating CMs from induced pluripotent stem cells (iPSC) derived from patients with catecholaminergic polymorphic ventricular tachycardia (CPVT), which is an inherited and severe cardiac disease. Ca2+ cycling studies have revealed substantial abnormalities in these CMs. Ca2+ transient analysis performed manually lacks accepted analysis criteria, and has both low throughput and high variability. To overcome these issues, we have developed a software tool, AnomalyExplorer based on interactive visualization, to assist in the classification of Ca2+ transient patterns detected in CMs. Here, we demonstrate the usability and capability of the software, and we also compare the analysis efficiency to manual analysis. We show that AnomalyExplorer is suitable for detecting normal and abnormal Ca2+ transients; furthermore, this method provides more defined and consistent information regarding the Ca2+ abnormality patterns and cell line specific differences when compared to manual analysis. This tool will facilitate and speed up the analysis of CM Ca2+ transients, making it both more accurate and user-independent. AnomalyExplorer can be exploited in Ca2+ cycling analysis to study basic disease pathology and the effects of different drugs.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0135806</identifier><identifier>PMID: 26308621</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Abnormalities ; Action Potentials - physiology ; Calcium ; Calcium - metabolism ; Calcium ions ; Calcium Signaling - physiology ; Cardiac arrhythmia ; Cardiomyocytes ; Cardiomyopathy ; Cells, Cultured ; Classification ; Computer programs ; Contraction ; Coronary artery disease ; Cycles ; Data analysis ; Disease ; Excitation Contraction Coupling ; Hand tools ; Heart ; Heart diseases ; Humans ; Induced Pluripotent Stem Cells - cytology ; Induced Pluripotent Stem Cells - metabolism ; Mutation ; Myocardial Contraction ; Myocytes, Cardiac - cytology ; Myocytes, Cardiac - metabolism ; Pluripotency ; Ryanodine Receptor Calcium Release Channel - metabolism ; Software ; Software development tools ; Stem cells ; Studies ; Tachycardia ; Tachycardia, Ventricular - physiopathology ; Transient analysis ; Usability ; Ventricle</subject><ispartof>PloS one, 2015-08, Vol.10 (8), p.e0135806-e0135806</ispartof><rights>2015 Penttinen et al. 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Abnormal Ca2+ cycling is linked to arrhythmogenesis, which is associated with cardiac disorders and heart failure. Accordingly, we have generated spontaneously beating CMs from induced pluripotent stem cells (iPSC) derived from patients with catecholaminergic polymorphic ventricular tachycardia (CPVT), which is an inherited and severe cardiac disease. Ca2+ cycling studies have revealed substantial abnormalities in these CMs. Ca2+ transient analysis performed manually lacks accepted analysis criteria, and has both low throughput and high variability. To overcome these issues, we have developed a software tool, AnomalyExplorer based on interactive visualization, to assist in the classification of Ca2+ transient patterns detected in CMs. Here, we demonstrate the usability and capability of the software, and we also compare the analysis efficiency to manual analysis. We show that AnomalyExplorer is suitable for detecting normal and abnormal Ca2+ transients; furthermore, this method provides more defined and consistent information regarding the Ca2+ abnormality patterns and cell line specific differences when compared to manual analysis. This tool will facilitate and speed up the analysis of CM Ca2+ transients, making it both more accurate and user-independent. AnomalyExplorer can be exploited in Ca2+ cycling analysis to study basic disease pathology and the effects of different drugs.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26308621</pmid><doi>10.1371/journal.pone.0135806</doi><oa>free_for_read</oa></addata></record> |
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subjects | Abnormalities Action Potentials - physiology Calcium Calcium - metabolism Calcium ions Calcium Signaling - physiology Cardiac arrhythmia Cardiomyocytes Cardiomyopathy Cells, Cultured Classification Computer programs Contraction Coronary artery disease Cycles Data analysis Disease Excitation Contraction Coupling Hand tools Heart Heart diseases Humans Induced Pluripotent Stem Cells - cytology Induced Pluripotent Stem Cells - metabolism Mutation Myocardial Contraction Myocytes, Cardiac - cytology Myocytes, Cardiac - metabolism Pluripotency Ryanodine Receptor Calcium Release Channel - metabolism Software Software development tools Stem cells Studies Tachycardia Tachycardia, Ventricular - physiopathology Transient analysis Usability Ventricle |
title | Novel Analysis Software for Detecting and Classifying Ca2+ Transient Abnormalities in Stem Cell-Derived Cardiomyocytes |
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