Dataset Information

Symmetric Projection Attractor Reconstruction analysis of murine electrocardiograms: Retrospective prediction of Scn5a^+/- genetic mutation attributable to Brugada syndrome.

ABSTRACT:

Background

Life-threatening arrhythmias resulting from genetic mutations are often missed in current electrocardiogram (ECG) analysis. We combined a new method for ECG analysis that uses all the waveform data with machine learning to improve detection of such mutations from short ECG signals in a mouse model.

Objective

We sought to detect consequences of Na⁺ channel deficiencies known to compromise action potential conduction in comparisons of Scn5a^+/- mutant and wild-type mice using short ECG signals, examining novel and standard features derived from lead I and II ECG recordings by machine learning algorithms.

Methods

Lead I and II ECG signals from anesthetized wild-type and Scn5a^+/- mutant mice of length 130 seconds were analyzed by extracting various groups of features, which were used by machine learning to classify the mice as wild-type or mutant. The features used were standard ECG intervals and amplitudes, as well as features derived from attractors generated using the novel Symmetric Projection Attractor Reconstruction method, which reformulates the whole signal as a bounded, symmetric 2-dimensional attractor. All the features were also combined as a single feature group.

Results

Classification of genotype using the attractor features gave higher accuracy than using either the ECG intervals or the intervals and amplitudes. However, the highest accuracy (96%) was obtained using all the features. Accuracies for different subgroups of the data were obtained and compared.

Conclusion

Detection of the Scn5a^+/- mutation from short mouse ECG signals with high accuracy is possible using our Symmetric Projection Attractor Reconstruction method.

SUBMITTER: Bonet-Luz E

PROVIDER: S-EPMC7962089 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: The electrocardiogram (ECG) is a key tool in patient management. Automated ECG analysis supports clinical decision-making, but traditional fiducial point identification discards much of the time-series data that captures the morphology of the whole waveform. Our Symmetric Projection Attractor Reconstruction (SPAR) method uses all the available data to provide a new visualization and quantification of the morphology and variability of any approximately periodic signal. We therefore applied SPAR to ECG signals to ascertain whether this more detailed investigation of ECG morphology adds clinical value. Methods: Our aim was to demonstrate the accuracy of the SPAR method in discriminating between two biologically distinct groups. As sex has been shown to influence the waveform appearance, we investigated sex differences in normal sinus rhythm ECGs. We applied the SPAR method to 9,007 10 second 12-lead ECG recordings from Physionet, which comprised; Dataset 1: 104 subjects (40% female), Dataset 2: 8,903 subjects (54% female). Results: SPAR showed clear visual differences between female and male ECGs (Dataset 1). A stacked machine learning model achieved a cross-validation sex classification accuracy of 86.3% (Dataset 2) and an unseen test accuracy of 91.3% (Dataset 1). The mid-precordial leads performed best in classification individually, but the highest overall accuracy was achieved with all 12 leads. Classification accuracy was highest for young adults and declined with older age. Conclusions: SPAR allows quantification of the morphology of the ECG without the need to identify conventional fiducial points, whilst utilizing of all the data reduces inadvertent bias. By intuitively re-visualizing signal morphology as two-dimensional images, SPAR accurately discriminated ECG sex differences in a small dataset. We extended the approach to a machine learning classification of sex for a larger dataset, and showed that the SPAR method provided a means of visualizing the similarities of subjects given the same classification. This proof-of-concept study therefore provided an implementation of SPAR using existing data and showed that subtle differences in the ECG can be amplified by the attractor. SPAR's supplementary analysis of ECG morphology may enhance conventional automated analysis in clinically important datasets, and improve patient stratification and risk management.