Match!

Deep Learning-Based Proarrhythmia Analysis Using Field Potentials Recorded From Human Pluripotent Stem Cells Derived Cardiomyocytes

Published on Jan 1, 2019in IEEE Journal of Translational Engineering in Health and Medicine2.075
· DOI :10.1109/JTEHM.2019.2907945
Zeinab Golgooni (Sharif University of Technology), Sara Mirsadeghi1
Estimated H-index: 1
(Royan Institute)
+ 4 AuthorsHamid R. Rabiee20
Estimated H-index: 20
(Sharif University of Technology)
Abstract
An early characterization of drug-induced cardiotoxicity may be possible by combining comprehensive in vitro proarrhythmia assay and deep learning techniques. We aimed to develop a method to automatically detect irregular beating rhythm of field potentials recorded from human pluripotent stem cells (hPSC) derived cardiomyocytes (hPSC-CM) by multi-electrode array (MEA) system. We included field potentials from 380 experiments, which were labeled as normal or arrhythmic by electrophysiology experts. Convolutional and recurrent neural networks (CNN and RNN) were employed for automatic classification of field potential recordings. A preparation phase was initially applied to split 60-s long recordings into a series of 5-s windows. Subsequently, the classification phase comprising of two main steps was designed and applied. The first step included the classification of 5-s windows by using a designated CNN. While, the results of 5-s window assessments were used as the input sequence to an RNN that aggregates these results in the second step. The output was then compared to electrophysiologist-level arrhythmia detection, resulting in 0.83 accuracy, 0.93 sensitivity, 0.70 specificity, and 0.80 precision. In summary, this paper introduces a novel method for automated analysis of “irregularity” in an in vitro model of cardiotoxicity experiments. Thus, our method may overcome the drawbacks of using predesigned features that restricts the classification performance to the comprehensiveness and the quality of the designed features. Furthermore, automated analysis may facilitate the quality control experiments through the procedure of drug development with respect to cardiotoxicity and avoid late drug attrition from market.
  • References (46)
  • Citations (0)
📖 Papers frequently viewed together
1 Citations
78% of Scinapse members use related papers. After signing in, all features are FREE.
References46
Newest
The Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative is developing and validating a mechanistic-based assessment of proarrhythmic risk of drugs. CiPA proposes to assess a drug's effect on multiple ion channels and integrate the effects in a computer model of the human cardiomyocyte to predict proarrhythmic risk. Unanticipated or missed effects will be assessed with human stem cell derived cardiomyocytes and electrocardiogram (ECG) analysis in early phase 1 clinical trials. This paper...
39 CitationsSource
#1Serkan Kiranyaz (Qatar University)H-Index: 23
#2Turker Ince (IUE: İzmir University of Economics)H-Index: 18
Last. Moncef Gabbouj (TUT: Tampere University of Technology)H-Index: 42
view all 3 authors...
Each year more than 7 million people die from cardiac arrhythmias. Yet no robust solution exists today to detect such heart anomalies right at the moment they occur. The purpose of this study was to design a personalized health monitoring system that can detect early occurrences of arrhythmias from an individual’s electrocardiogram (ECG) signal. We first modelled the common causes of arrhythmias in the signal domain as a degradation of normal ECG beats to abnormal beats. Using the degradation mo...
12 CitationsSource
#1Geert J. S. Litjens (Radboud University Nijmegen)H-Index: 23
#2Thijs Kooi (Radboud University Nijmegen)H-Index: 6
Last. Clara I. Sánchez (Radboud University Nijmegen)H-Index: 25
view all 9 authors...
Abstract Deep learning algorithms, in particular convolutional networks, have rapidly become a methodology of choice for analyzing medical images. This paper reviews the major deep learning concepts pertinent to medical image analysis and summarizes over 300 contributions to the field, most of which appeared in the last year. We survey the use of deep learning for image classification, object detection, segmentation, registration, and other tasks. Concise overviews are provided of studies per ap...
1,601 CitationsSource
#1Xavier LigneauH-Index: 27
#2Rashmi R. ShahH-Index: 14
Last. Jean-Charles SchwartzH-Index: 75
view all 10 authors...
Background and Purpose We evaluated the concordance of results from two sets of nonclinical cardiovascular safety studies on pitolisant. Experimental Approach Nonclinical studies envisaged both in the International Conference on Harmonization (ICH) S7B guideline and Comprehensive in vitro Pro-arrhythmia Assay (CiPA) initiative were undertaken. The CiPA initiative included in vitro ion channels, stem cell-derived human ventricular myocytes, and in silico modelling to simulate human ventricular el...
5 CitationsSource
#1Sara Pahlavan (Academic Center for Education, Culture and Research)H-Index: 6
#2Marziyeh Shalchi Tousi (Academic Center for Education, Culture and Research)H-Index: 1
Last. Hossein Baharvand (University of Science and Culture)H-Index: 44
view all 7 authors...
Cardiac arrhythmias are major life-threatening conditions. The landmark discovery of induced pluripotent stem cells has provided a promising in vitro system for modeling hereditary cardiac arrhythmias as well as drug development and toxicity testing. Nowadays, nutraceuticals are frequently used as supplements for cardiovascular therapy. Here we studied the cardiac effects of hawthorn (Crataegus pentagyna) leaf extract using cardiomyocytes (CMs) differentiated from healthy human embryonic stem ce...
5 CitationsSource
#1Jose Vicente (CDER: Center for Drug Evaluation and Research)H-Index: 19
#2Meisam Hosseini (CDER: Center for Drug Evaluation and Research)H-Index: 3
Last. David G. Strauss (CDER: Center for Drug Evaluation and Research)H-Index: 26
view all 4 authors...
Abstract The ECG plays a critical role in the thorough QT study. This clinical study is part of the assessment of proarrhythmic potential of drugs under the current regulatory paradigm. While the current paradigm has been successful in preventing drugs with unexpected QT prolongation or torsade risk from reaching the market, the focus on QT prolongation has likely resulted in potentially beneficial compounds with minimal torsade risk being dropped from development. The Comprehensive in vitro Pro...
9 CitationsSource
Abstract With the aim of reconsidering ICH S7B and E14 guidelines, a new in vitro assay system has been subjected to worldwide validation to establish a better prediction platform for potential drug-induced QT prolongation and the consequent TdP in clinical practice. In Japan, CSAHi HEART team has been working on hiPS-CMs in the MEA (hiPS-CMs/MEA) under a standardized protocol and found no inter-facility or lot-to-lot variability for proarrhythmic risk assessment of 7 reference compounds. In thi...
14 CitationsSource
#1Gary A. GintantH-Index: 24
#2Bernard FerminiH-Index: 11
Last. David G. Strauss (CDER: Center for Drug Evaluation and Research)H-Index: 26
view all 4 authors...
Nonclinical studies of drug effects with human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) provide new possibilities for evaluating drug safety and efficacy. The Comprehensive In Vitro Proarrhythmia Assay (CiPA) paradigm provides lessons from the cardiac field that also apply to drug studies with other stem cell-based assays.
25 CitationsSource
#1Luca Sala (LUMC: Leiden University Medical Center)H-Index: 14
#2Dorien Ward-van Oostwaard (LUMC: Leiden University Medical Center)H-Index: 23
Last. Milena Bellin (LUMC: Leiden University Medical Center)H-Index: 19
view all 5 authors...
Cardiomyocytes can now be derived with high efficiency from both human embryonic and human induced-Pluripotent Stem Cells (hPSC). hPSC-derived cardiomyocytes (hPSC-CMs) are increasingly recognized as having great value for modeling cardiovascular diseases in humans, especially arrhythmia syndromes. They have also demonstrated relevance as in vitro systems for predicting drug responses, which makes them potentially useful for drug-screening and discovery, safety pharmacology and perhaps eventuall...
4 CitationsSource
#1Francesca Stillitano (ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 8
#2Jens Hansen (ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 8
Last. Jean-Sébastien Hulot (ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 43
view all 18 authors...
Common medications can disturb the electrical signals that cause the heart to beat, potentially resulting in sudden death. Many of the drugs that have these “cardiotoxic” effects were not designed to affect the heart, and include anti-allergenics and anti-vomiting drugs. In general, only a small proportion of individuals treated with these drugs will be at risk of fatal side effects; this risk variation is thought to be due to genetic differences. If these people could be reliably identified, th...
28 CitationsSource
Cited By0
Newest
Heart diseases are highly ranked among the leading causes of mortality in the world. They have various types including vascular, ischemic, and hypertensive heart disease. A large number of medical features are reported for patients in the Electronic Health Records (EHR) that allow physicians to diagnose and monitor heart disease. We collected a dataset from Medica Norte Hospital in Mexico that includes 800 records and 141 indicators such as age, weight, glucose, blood pressure rate, and clinical...
Source
#1Olurotimi Bolonduro (Tufts University)H-Index: 1
#2Breanna M. Duffy (Tufts University)
Last. Brian P. Timko (Tufts University)H-Index: 22
view all 5 authors...
Effective strategies in cardiac tissue engineering require matrices that recapitulate the mechanical, topographic and electrical cues present in the native extracellular matrix. In this review, we discuss recent efforts in materials science and nanotechnology to achieve functional three-dimensional (3D) scaffolds that modulate and monitor cardiac tissue function. We consider key design considerations, including choice of biopolymer matrix, cell sources, and delivery methods for eventual therapie...
Source