Unknown

Dataset Information

0

Prediction of drug-induced nephrotoxicity and injury mechanisms with human induced pluripotent stem cell-derived cells and machine learning methods.


ABSTRACT: The renal proximal tubule is a main target for drug-induced toxicity. The prediction of proximal tubular toxicity during drug development remains difficult. Any in vitro methods based on induced pluripotent stem cell-derived renal cells had not been developed, so far. Here, we developed a rapid 1-step protocol for the differentiation of human induced pluripotent stem cells (hiPSC) into proximal tubular-like cells. These proximal tubular-like cells had a purity of >90% after 8 days of differentiation and could be directly applied for compound screening. The nephrotoxicity prediction performance of the cells was determined by evaluating their responses to 30 compounds. The results were automatically determined using a machine learning algorithm called random forest. In this way, proximal tubular toxicity in humans could be predicted with 99.8% training accuracy and 87.0% test accuracy. Further, we studied the underlying mechanisms of injury and drug-induced cellular pathways in these hiPSC-derived renal cells, and the results were in agreement with human and animal data. Our methods will enable the development of personalized or disease-specific hiPSC-based renal in vitro models for compound screening and nephrotoxicity prediction.

SUBMITTER: Kandasamy K 

PROVIDER: S-EPMC4515747 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications

Prediction of drug-induced nephrotoxicity and injury mechanisms with human induced pluripotent stem cell-derived cells and machine learning methods.

Kandasamy Karthikeyan K   Chuah Jacqueline Kai Chin JK   Su Ran R   Huang Peng P   Eng Kim Guan KG   Xiong Sijing S   Li Yao Y   Chia Chun Siang CS   Loo Lit-Hsin LH   Zink Daniele D  

Scientific reports 20150727


The renal proximal tubule is a main target for drug-induced toxicity. The prediction of proximal tubular toxicity during drug development remains difficult. Any in vitro methods based on induced pluripotent stem cell-derived renal cells had not been developed, so far. Here, we developed a rapid 1-step protocol for the differentiation of human induced pluripotent stem cells (hiPSC) into proximal tubular-like cells. These proximal tubular-like cells had a purity of >90% after 8 days of differentia  ...[more]

Similar Datasets

| S-EPMC8769702 | biostudies-literature
| S-EPMC7254069 | biostudies-literature
| S-EPMC8769705 | biostudies-literature
| S-EPMC7020573 | biostudies-literature
| S-EPMC8046881 | biostudies-literature
| S-EPMC9143325 | biostudies-literature
| S-EPMC6011237 | biostudies-literature
2013-01-01 | E-GEOD-29210 | biostudies-arrayexpress
| S-EPMC7702310 | biostudies-literature
| S-EPMC3146072 | biostudies-literature