OrgaSegment: deep-learning based organoid segmentation to quantify CFTR dependent fluid secretion

作者：Juliet W. Lefferts, Suzanne Kroes, Matthew B. Smith, Paul J Niemöller, Natascha D.A. Nieuwenhuijze, Heleen N. Sonneveld van Kooten, Cornelis Korstiaan van der Ent, Jeffrey Matthijn Beekman, Sam F.B. van Beuningen · 发表于：Communications Biology · 年份：2024 · DOI：10.1038/s42003-024-05966-4 · 被引用次数：47 · 研究领域：Cystic Fibrosis Research Advances、Neonatal Respiratory Health Research、Inhalation and Respiratory Drug Delivery

Epithelial ion and fluid transport studies in patient-derived organoids (PDOs) are increasingly being used for preclinical studies, drug development and precision medicine applications. Epithelial fluid transport properties in PDOs can be measured through visual changes in organoid (lumen) size. Such organoid phenotypes have been highly instrumental for the studying of diseases, including cystic fibrosis (CF), which is characterized by genetic mutations of the CF transmembrane conductance regulator (CFTR) ion channel. Here we present OrgaSegment, a MASK-RCNN based deep-learning segmentation model allowing for the segmentation of individual intestinal PDO structures from bright-field images. OrgaSegment recognizes spherical structures in addition to the oddly-shaped organoids that are a hallmark of CF organoids and can be used in organoid swelling assays, including the new drug-induced swelling assay that we show here. OrgaSegment enabled easy quantification of organoid swelling and could discriminate between organoids with different CFTR mutations, as well as measure responses to CFTR modulating drugs. The easy-to-apply label-free segmentation tool can help to study CFTR-based fluid secretion and possibly other epithelial ion transport mechanisms in organoids.