CM and DR Engine Details. (a) Workflow of the CM Engine. Processing of images typically begins with multi-plate image files in a "Parent Directory." Prior to processing, CM Engine copies the multi-plate image files to the "original_scans" folder. The rough crop algorithm divides multi-plate images into individual plate images and moves them to the "rough_crops" folder. Rough cropped images that are successfully aligned and fine cropped are moved to the "fine_crops" folder. If unsuccessful, the affected images are moved to the "fine_crop_errors" folder. In most cases, the images in the "error" folder can be manually aligned and fine cropped and then moved to the "fine_crops" folder for processing in a subsequent run of the CM Engine. Next, colonies are measured, the results are appended to a log file and the images are moved to the "measurements_passed" folder. In the event of a measurement error, results are not appended to the log file and the image is moved to the "measurement_errors" folder (See Additional File 1 for details). Red "error" folders are also marked with a dagger (†). (b) Image of a 1536 SDL screen plate containing four 2 × 2 replicates of each strain (384 strains total) that has been fine cropped by the CM Engine. (c) DR Engine normalized representation of the plate in b based on Standard mode measurements by the CM Engine. Circles are generated for each yeast colony on the plate. Circle size and color is directly correlated to normalized colony size. Colony color ranges from light gray for small colonies, to black for those that are equal to the plate median, to blue for those colonies larger than the plate median. Colonies highlighted in yellow are below 25% of the median. Colonies highlighted in red have been marked for exclusion from statistical consideration.