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Aggregate entropy scoring for quantifying activity across endpoints with irregular correlation structure.

ABSTRACT: Robust computational approaches are needed to characterize systems-level responses to chemical perturbations in environmental and clinical toxicology applications. Appropriate characterization of response presents a methodological challenge when dealing with diverse phenotypic endpoints measured using in vivo systems. In this article, we propose an information-theoretic method named Aggregate Entropy (AggE) and apply it to scoring multiplexed, phenotypic endpoints measured in developing zebrafish (Danio rerio) across a broad concentration-response profile for a diverse set of 1060 chemicals. AggE accurately identified chemicals with significant morphological effects, including single-endpoint effects and multi-endpoint responses that would have been missed by univariate methods, while avoiding putative false-positives that confound traditional methods due to irregular correlation structure. By testing AggE in a variety of high-dimensional real and simulated datasets, we have characterized its performance and suggested implementation parameters that can guide its application across a wide range of experimental scenarios.

SUBMITTER: Zhang G

PROVIDER: S-EPMC4905797 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Aggregate entropy scoring for quantifying activity across endpoints with irregular correlation structure.

Zhang Guozhu G Marvel Skylar S Truong Lisa L Tanguay Robert L RL Reif David M DM

Reproductive toxicology (Elmsford, N.Y.) 20160427

Robust computational approaches are needed to characterize systems-level responses to chemical perturbations in environmental and clinical toxicology applications. Appropriate characterization of response presents a methodological challenge when dealing with diverse phenotypic endpoints measured using in vivo systems. In this article, we propose an information-theoretic method named Aggregate Entropy (AggE) and apply it to scoring multiplexed, phenotypic endpoints measured in developing zebrafis ...[more]

PMID: 27132190

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Project description:BackgroundScreening the general public for atrial fibrillation (AF) may enable early detection and timely intervention, which could potentially decrease the incidence of stroke. Existing screening methods require professional monitoring and involve high costs. AF is characterized by an irregular irregularity of the cardiac rhythm, which may be detectable using an index quantifying and visualizing this type of irregularity, motivating wide screening programs and promoting the research of AF patient subgroups and clinical impact of AF burden.MethodsWe calculated variability, normality and mean of the difference between consecutive RR interval series (denoted as modified entropy scale-MESC) to quantify irregular irregularities. Based on the variability and normality indices calculated for long 1-lead ECG records, we created a plot termed a regularogram (RGG), which provides a visual presentation of irregularly irregular rates and their burden in a given record. To inspect the potency of these indices, they were applied to train and test a machine learning classifier to identify AF episodes in gold-standard, publicly available databases (PhysioNet) that include recordings from both patients with AF and/or other rhythm disturbances, and from healthy volunteers. The classifier was trained and validated on one database and tested on three other databases.ResultsIrregular irregularities were identified using normality, variability and mean MESC indices. The RGG displayed visually distinct differences between patients with vs. without AF and between patients with different levels of AF burden. Training a simple, explainable machine learning tool integrating these three indices enabled AF detection with 99.9% accuracy, when trained on the same person, and 97.8%, when trained on patients from a different database. Comparison to other RR interval-based AF detection methods that utilize signal processing, classic machine learning and deep learning techniques, showed superiority of our suggested method.ConclusionVisualizing and quantifying irregular irregularities will be of value for both rapid visual inspection of long Holter recordings for the presence and the burden of AF, and for machine learning classification to identify AF episodes. A free online tool for calculating the indices, drawing RGGs and estimating AF burden, is available.

Dataset Information

Aggregate entropy scoring for quantifying activity across endpoints with irregular correlation structure.

Publications

Aggregate entropy scoring for quantifying activity across endpoints with irregular correlation structure.

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