TitleAggregate entropy scoring for quantifying activity across endpoints with irregular correlation structure.
Publication TypeJournal Article
Year of Publication2016
AuthorsZhang, G, Marvel, S, Truong, L, Tanguay, RL, Reif, DM
JournalReprod Toxicol
Date Published2016 07
KeywordsAnimals, Embryo, Nonmammalian, Entropy, Flame Retardants, High-Throughput Screening Assays, Models, Theoretical, Phenotype, Teratogens, Zebrafish

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.

Alternate JournalReprod. Toxicol.
PubMed ID27132190
PubMed Central IDPMC4905797
Grant ListP30 ES025128 / ES / NIEHS NIH HHS / United States
R01 ES023788 / ES / NIEHS NIH HHS / United States
T32 ES007329 / ES / NIEHS NIH HHS / United States
R01 ES019604 / ES / NIEHS NIH HHS / United States
RC4 ES019764 / ES / NIEHS NIH HHS / United States
P42 ES016465 / ES / NIEHS NIH HHS / United States
P30 ES000210 / ES / NIEHS NIH HHS / United States
P42 ES005948 / ES / NIEHS NIH HHS / United States