RT Journal Article SR Electronic T1 Quantitative assessment of eye phenotypes for functional genetic studies using Drosophila melanogaster JF bioRxiv FD Cold Spring Harbor Laboratory SP 036368 DO 10.1101/036368 A1 Janani Iyer A1 Qingyu Wang A1 Thanh Le A1 Lucilla Pizzo A1 Sebastian Grönke A1 Surendra S. Ambegaokar A1 Yuzuru Imai A1 Ashutosh Srivastava A1 Beatriz Llamusí Troisí A1 Graeme Mardon A1 Ruben Artero A1 George R. Jackson A1 Adrian M. Isaacs A1 Linda Partridge A1 Bingwei Lu A1 Justin P. Kumar A1 Santhosh Girirajan YR 2016 UL http://biorxiv.org/content/early/2016/01/15/036368.abstract AB About two-thirds of the vital genes in the Drosophila genome are involved in eye development, making the fly eye an excellent genetic system to study cellular function and development, neurodevelopment/degeneration, and complex diseases such as cancer and diabetes. We developed a novel computational method, implemented as Flynotyper software (http://flynotyper.sourceforge.net), to quantitatively assess the morphological defects in the Drosophila eye resulting from genetic alterations affecting basic cellular and developmental processes. Flynotyper utilizes a series of image processing operations to automatically detect the fly eye and the individual ommatidium, and calculates a phenotypic score as a measure of the disorderliness of ommatidial arrangement in the fly eye. As a proof of principle, we tested our method by analyzing the defects due to eye-specific knockdown of Drosophila orthologs of 12 neurodevelopmental genes to accurately document differential sensitivities of these genes to dosage alteration. We also evaluated eye images from six independent studies assessing the effect of overexpression of repeats, candidates from peptide library screens, and modifiers of neurotoxicity and developmental processes on eye morphology, and show strong concordance with the original assessment. We further demonstrate the utility of this method by analyzing 16 modifiers of sine oculis obtained from two genome-wide deficiency screens of Drosophila and accurately quantifying the effect of its enhancers and suppressors during eye development. Our method will complement existing assays for eye phenotypes and increase the accuracy of studies that use fly eyes for functional evaluation of genes and genetic interactions.