PUBLICATION
Aggregate Entropy Scoring for Quantifying Activity across Endpoints with Irregular Correlation Structure
- Authors
- Zhang, G., Marvel, S., Truong, L., Tanguay, R.L., Reif, D.M.
- ID
- ZDB-PUB-160502-1
- Date
- 2016
- Source
- Reproductive toxicology (Elmsford, N.Y.) 62: 92-9 (Journal)
- Registered Authors
- Tanguay, Robyn L.
- Keywords
- Chemical Biology, Developmental Neurotoxicology, High Throughput Screening, Morphology, Multiplexed Assays, ToxCast, Zebrafish
- MeSH Terms
-
- Animals
- Embryo, Nonmammalian
- Entropy
- Flame Retardants/toxicity
- High-Throughput Screening Assays*
- Models, Theoretical*
- Phenotype
- Teratogens/toxicity*
- Zebrafish/embryology*
- PubMed
- 27132190 Full text @ Reprod. Toxicol.
Citation
Zhang, G., Marvel, S., Truong, L., Tanguay, R.L., Reif, D.M. (2016) Aggregate Entropy Scoring for Quantifying Activity across Endpoints with Irregular Correlation Structure. Reproductive toxicology (Elmsford, N.Y.). 62:92-9.
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 1,060 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping