Deep learning predicts the differentiation of kidney organoids derived from human induced pluripotent stem cells

Abstract

Background: Kidney organoids derived from human pluripotent stem cells (hPSCs) contain multilineage nephrogenic progenitor cells andcan recapitulate the development of the kidney. Kidney organoids derived from hPSCs have the potential to be applied in regenerative medicineas well as renal disease modeling, drug screening, and nephrotoxicity testing. Despite biotechnological advances, individual differencesin morphological and growth characteristics among kidney organoids need to be addressed before clinical and commercial application. Inthis study, we hypothesized that an automated noninvasive method based on deep learning of bright-field images of kidney organoids canpredict their differentiation status.Methods: Bright-field images of kidney organoids were collected on day 18 after differentiation. To train convolutional neural networks(CNNs), we utilized a transfer learning approach. CNNs were trained to predict the differentiation of kidney organoids on bright-field imagesbased on the messenger RNA expression of renal tubular epithelial cells as well as podocytes.Results: The best prediction model was DenseNet121 with a total Pearson correlation coefficient score of 0.783 on a test dataset. W classifiedthe kidney organoids into two categories: organoids with above-average gene expression (Positive) and those with below-average geneexpression (Negative). Comparing the best-performing CNN with human-based classifiers, the CNN algorithm had a receiver operating characteristic-area under the curve (AUC) score of 0.85, while the experts had an AUC score of 0.48.Conclusion: These results confirmed our original hypothesis and demonstrated that our artificial intelligence algorithm can successfully recognizethe differentiation status of kidney organoids.