Machine learning discriminates a movement disorder in a zebrafish model of Parkinson's disease.
Animal models of human disease provide an in vivo system that can reveal molecular mechanisms by which mutations cause pathology, and, moreover, have the potential to provide a valuable tool for drug development. Here, we have developed a zebrafish model of Parkinson's disease (PD) together with a novel method to screen for movement disorders in adult fish, pioneering a more efficient drug-testing route. Mutation of the PARK7 gene (which encodes DJ-1) is known to cause monogenic autosomal recessive PD in humans, and, using CRISPR/Cas9 gene editing, we generated a Dj-1 loss-of-function zebrafish with molecular hallmarks of PD. To establish whether there is a human-relevant parkinsonian phenotype in our model, we adapted proven tools used to diagnose PD in clinics and developed a novel and unbiased computational method to classify movement disorders in adult zebrafish. Using high-resolution video capture and machine learning, we extracted novel features of movement from continuous data streams and used an evolutionary algorithm to classify parkinsonian fish. This method will be widely applicable for assessing zebrafish models of human motor diseases and provide a valuable asset for the therapeutics pipeline. In addition, interrogation of RNA-seq data indicate metabolic reprogramming of brains in the absence of Dj-1, adding to growing evidence that disruption of bioenergetics is a key feature of neurodegeneration.This article has an associated First Person interview with the first author of the paper.
['Hughes|Gideon L|GL|', 'Lones|Michael A|MA|', 'Bedder|Matthew|M|', 'Currie|Peter D|PD|', 'Smith|Stephen L|SL|', 'Pownall|Mary Elizabeth|ME|0000-0003-2329-5844']
D000465:Algorithms D000483:Alleles D000818:Animals D001483:Base Sequence D001921:Brain D004195:Disease Models, Animal D059290:Dopaminergic Neurons D020869:Gene Expression Profiling D018390:Gene Targeting D000069550:Machine Learning D009068:Movement D009069:Movement Disorders D009154:Mutation D010300:Parkinson Disease D000071617:Protein Deglycase DJ-1 D015027:Zebrafish
Parkinson's disease PARK7 DJ-1 Video capture Artificial intelligence Gene targeting