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ZebraZoom: Kinematic analysis for drug and genetic screening in zebrafish

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A zebrafish tracker to aid drug development

A free, open-source software package will allow scientists to examine with greater clarity the effects of candidate drugs on behaviour, facilitating the discovery of new cures and therapies.

Health

Before new treatments for neurological disorders such as Alzheimer’s or epilepsy can reach patients, potential drugs need to be carefully screened to assess their efficacy and safety. Tests on rodents and primates – which have historically been used as reference animal models – are long and costly, not to mention increasingly controversial. Larval zebrafish have emerged in recent years as a potential time- and cost-effective alternative. One reason for this is that the zebrafish genome is very similar to that of humans. Some 84 % of genes associated with diseases in humans have zebrafish counterparts. There are other advantages too. Each pair of male and female zebrafish will produce hundreds of eggs every week, which means drug screening experiments can be performed with high throughput. Studying how the larvae move is one way researchers can examine the effects of drugs on the animals. “A key challenge is that zebrafish larvae are small, with a body length of just 4 mm, and move rapidly,” explains ZebraZoom project coordinator Claire Wyart, group leader at the Paris Brain Institute (ICM) in France. “This means that analysis cannot just be done manually. It requires sophisticated image processing.” Current analysis solutions rely on either expensive commercial software or open-source image processing software that offers limited applications. Wyart identified a pressing need for freely available technology, capable of capturing in high resolution the behavioural movements of zebrafish when they respond to drugs.

Tracking animal behaviour

Wyart, and her ICM colleague Olivier Mirat, began developing their tracking software, called ZebraZoom, in 2010. The program, which is easy to install and use, detects specific movements and extracts data on these movement patterns. The purpose of this EU-funded project was to evaluate the market potential for their innovation, and to develop marketing and business plans targeting end users. “We found that our primary target users were academic research labs who need to quantify the behaviour of animal models, as well as animals in the wild,” says Wyart. “We are also looking to work with pharmaceutical companies in the future.” Feedback was received from 10 research groups using ZebraZoom software. “We learned a tremendous amount from these interactions, and are now working on a new revised version,” adds Wyart. “For example, we have tried to make it more user-friendly and adaptable, with new features such as the tracking of eyes and tail.”

New drug discoveries

Unlike commercial software solutions, ZebraZoom is free to download and open-source. “This means that everyone can see and inspect the source code that it relies on, report potential bugs and even contribute by writing new code,” notes Wyart. “Our vision is to provide free software and free initial support. We also envisage a paid service for users who require more support, or would like us to create custom features.” Tracking and behaviour analysis in the lab – and the wild – is critical to understanding biological systems. The emergence of zebrafish as a viable model for study has opened the door to new possible discoveries, and Wyart is hopeful that ZebraZoom will help to make this happen. “Our efforts will help scientists to find subtle but important effects of drugs and mutations,” she says. “This could lead to the discovery of cures for diseases.”

Keywords

ZebraZoom, neurological, zebrafish, drugs, genes, genome, software

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