Towards automated high-throughput screening of C. elegans on agar

TL;DR

This paper presents a computer vision approach for automating the analysis of high-throughput screening experiments with C. elegans worms, focusing on segmentation and phenotype detection to match expert accuracy.

Contribution

The authors developed a robust segmentation algorithm for worms in brightfield images and combined it with fluorescence detection to classify phenotypes automatically.

Findings

Segmentation accuracy comparable to human experts.

Reliable detection of subtle fluorescence-based phenotypes.

Advancement towards fully automated high-throughput screening.

Abstract

High-throughput screening (HTS) using model organisms is a promising method to identify a small number of genes or drugs potentially relevant to human biology or disease. In HTS experiments, robots and computers do a significant portion of the experimental work. However, one remaining major bottleneck is the manual analysis of experimental results, which is commonly in the form of microscopy images. This manual inspection is labor intensive, slow and subjective. Here we report our progress towards applying computer vision and machine learning methods to analyze HTS experiments that use Caenorhabditis elegans (C. elegans) worms grown on agar. Our main contribution is a robust segmentation algorithm for separating the worms from the background using brightfield images. We also show that by combining the output of this segmentation algorithm with an algorithm to detect the fluorescent dye, Nile Red, we can reliably distinguish different fluorescence-based phenotypes even though the visual differences are subtle. The accuracy of our method is similar to that of expert human analysts. This new capability is a significant step towards fully automated HTS experiments using C. elegans.