Automated morphological feature assessment for zebrafish embryo developmental toxicity screens


Detection of developmental phenotypes in zebrafish embryos typically involves a
visual assessment and scoring of morphological features by an individual
researcher. Subjective scoring could impact results and be of particular concern
when phenotypic effect patterns are also used as a diagnostic tool to classify
compounds. Here we introduce a quantitative morphometric approach based on
image analysis of zebrafish embryos. A software called FishInspector was developed
to detect morphological features from images collected using an automated system
to position zebrafish embryos. The analysis was verified and compared with visual
assessments of three participating laboratories using three known developmental
toxicants (methotrexate, dexamethasone and topiramate) and two negative
compounds (loratadine and glibenclamide). The quantitative approach exhibited
higher sensitivity and made it possible to compare patterns of effects with the
potential to establish a grouping and classification of developmental toxicants. Our
approach improves the robustness of phenotype scoring and reliability of assay
performance and, hence, is anticipated to improve the predictivity of developmental
toxicity screening using the zebrafish embryo.


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