PT  - JOURNAL ARTICLE
AU  - Anna S. Monzel
AU  - Kathrin Hemmer
AU  - Tony Kaoma Mukendi
AU  - Philippe Lucarelli
AU  - Isabel Rosety
AU  - Alise Zagare
AU  - Silvia Bolognin
AU  - Paul Antony
AU  - Sarah L. Nickels
AU  - Rejko Krueger
AU  - Francisco Azuaje
AU  - Jens C. Schwamborn
TI  - Machine learning-assisted neurotoxicity prediction in human midbrain organoids
AID  - 10.1101/774240
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 774240
4099  - http://biorxiv.org/content/early/2019/09/19/774240.short
4100  - http://biorxiv.org/content/early/2019/09/19/774240.full
AB  - A major challenge in the field of neurodegenerative diseases is the poor translation of pre-clinical models to clinical applications. The human brain is an immensely complex structure, which makes it difficult to recapitulate its development, function and disorders. In the recent years, brain organoids derived from human induced pluripotent stem cells have risen as novel tools to study neurodegenerative diseases such as Parkinson’s disease (PD). PD is a multifactorial disorder, with aging, genetics and environmental factors as key etiological elements. The majority of the PD cases are idiopathic and proposed to result from a complex interaction between genetic predisposition and environmental exposure. Consequently, the identification of potentially disease causing environmental factors is of critical importance. Organoids, as complex multi-cellular tissue proxies, are an ideal tool to study cellular response to environmental changes. However, with increasing complexity of the system, usage of quantitative tools becomes challenging. This led us to develop an automated high-content image analysis pipeline for image-based cell profiling in the organoid system. Here, we introduce a midbrain organoid system that recapitulates features of neurotoxin-induced PD, representing a platform for machine-learning-assisted prediction of neurotoxicity in high-content imaging data. This model is a valuable tool for advanced in vitro PD modeling and for the screening of putative neurotoxic compounds.