TY - JOUR
T1 - OrgaSegment
T2 - deep-learning based organoid segmentation to quantify CFTR dependent fluid secretion
AU - Lefferts, Juliet W
AU - Kroes, Suzanne
AU - Smith, Matthew B
AU - Niemöller, Paul J
AU - Nieuwenhuijze, Natascha D A
AU - Sonneveld van Kooten, Heleen N
AU - van der Ent, Cornelis K
AU - Beekman, Jeffrey M
AU - van Beuningen, Sam F B
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/3/13
Y1 - 2024/3/13
N2 - 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.
AB - 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.
KW - Cystic Fibrosis Transmembrane Conductance Regulator/genetics
KW - Cystic Fibrosis/genetics
KW - Deep Learning
KW - Humans
KW - Intestines
KW - Organoids
UR - http://www.scopus.com/inward/record.url?scp=85187749238&partnerID=8YFLogxK
U2 - 10.1038/s42003-024-05966-4
DO - 10.1038/s42003-024-05966-4
M3 - Article
C2 - 38480810
SN - 2399-3642
VL - 7
JO - Communications biology
JF - Communications biology
IS - 1
M1 - 319
ER -