Automated zebrafish screening for myeloid leukemia drug discovery

Automated zebrafish screening for myeloid leukemia drug discovery

Thought leaderDr. Elspeth Payne & Dr. Alexandra LubinUCL Cancer Institute

In this interview, NewsMedical talks to Elspeth Payne and Alexandra Lubin, cancer researchers at the UCL Cancer Institute in London, about how they use AI-powered analysis software to study myeloid leukemias in an automated, high-throughput manner using zebrafish models. Athena. This affordable software solution is available for download on a novel pay-per-use basis.

Could you please introduce what you do and briefly describe your research?

Elspeth Payne:My name is Beth Payne and I am a clinical scientist. My lab works on blood cancers, particularly myeloid malignancies,and I also look after patients in the hospital. We use a combination of zebrafish modeling and drug screening alongside primary patient material to study andbetterunderstand the development myeloid leukemias and different ways we might treat them in the future.

Alexandra Lubin:My name is Alex Lubin. I am a postdoctoral researcher in Beth Payne's lab. I work on zebrafish models of myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Drug screening is my main project, and I would like to perform drug screening in hematopoietic stem cells in the tail of zebrafish to look for synthetic lethality.

How did you perform the analysis of zebrafish before using Athena software?

Alexandra Lubin:When I look at stem cells in my drug screening, I'm trying to measure a change in cell number in a fish. To do this manually, all individual fluorescent cells in the tail must be counted. This means you have to put each fish under a microscope, go through it and count it, which is very time consuming. That's why we started looking for an automated approach.

What challenges do you face when it comes to getting the data you need?

Beth Payne:We have developed some methods for drug screening, and although zebrafish is a great model for this, getting the right throughput has been a challenge. Although there are many different platforms one can use, they usually have customized solutions for analyzing the data. This means that developing each new screen is both costly and takes a long time to get something that works for your purpose.

At what point did you move away from manual imaging and image analysis and look for automated solutions?

Beth Payne:In terms of automated screening, we've probably been looking for a solution for the last five to ten years. We revisited this challenge every few years as a key goal and asked ourselves, “How can we make this more time efficient?” Imaging and manual cell counting are necessary for proper data quantification, but we thought it would be a huge time saver if it could be automated. Not only for the time needed for these steps, but also to open up a whole range of possibilities for using such a platform for other experiments.

What are the biggest challenges when sampling with a manual workflow?

Alexandra Lubin:The biggest challenge with the manual method is that it is time-consuming. It's not particularly difficult, but it does mean spending hours and hours at the microscope. The other main problem with this is that you cannot achieve large sample sizes. If you want to do something like a drug screen, the strength lies in the ability to analyze many samples.

What has this technology brought to your lab?

Beth Payne:What has been helpful for this system is that we use it for all indications in addition to drug screening. For example, if we have a transgenic or even an in situ object that we want to image and look at in high content detail, we use the Athena instead of doing it manually.

The other great thing about the system is that it is flexible and you can optimize it for a different assay relatively quickly because the system is user-friendly. The company offers a lot of support to help us when we encounter difficulties.

I would say that overall it allows us to power our experiments much better because instead of just 20 embryos we can use 200 for the same processing time. In fact, it takes significantly less time than it would have otherwise. Overall, it offers more flexibility in terms of the experiments we can plan and the kind of performance we can get from the data output Athena.

AI-assisted analysis of a brightfield image of a zebrafish larva to identify internal anatomy in combination with detection of GFP-tagged hematopoietic stem cells. GFP-labeled cells present only in the tail can be counted selectively. Photo credit: IDEA Bio-Medical

Azo: When you started working on the Athena software, how long did it take you to become independent and productive with it?

Alexandra Lubin:When I first came across them Athena Software, there was a lot of development going on. This gave room for a lot of discussion with IDEA Bio-Medical about what we wanted from the software, what would be useful and highlight areas for improvement.

After commissioning, the transition period from the first use of the software to complete independence was relatively short.

How does this compare to other instruments you use, for example compared to manual microscopes?

Alexandra Lubin:This was a unique experience in that we had more contact with IDEA Bio-Medical than we normally would. I've never used another system like this so I don't have a direct comparison, but it is excellent and extremely practical software.

How long does it take you to analyze all your fish samples and how does that compare to previous times?

Alexandra Lubin:If we do these experiments manually, we can only examine about a hundred fish at a time. However, this takes so much time, but once we started, the Athena we can increase this number.

How many fish I screen depends on how well-behaved the fish are, like everyone you work with Zebrafish you'll know. It is possible to screen hundreds (of fish) in a short period of time as it only takes about 30 minutes between loading the plate and receiving results for about a hundred fish, whereas previously this would have taken a whole day.

What do you do if you need assistance using the software? Who supports you and how?

Alexandra Lubin:When I need assistance with the software, I contact the team at IDEA Bio-Medical. They have been really helpful and offer a collaborative partnership. I provide them with pictures; They support us – it works smoothly.

What was the point at which you thought the Athena software would be useful for your research?

Alexandra Lubin:When I started this drug screening, we knew we had to introduce automation because it would not be possible to screen thousands of compounds manually. As we started looking at different methods, it became clear how easy the system was to use and how flexible it was. In addition, we were attracted by the fact Athena allowed us to branch out and change it as needed.

Where do you see your work next and its impact?

Beth Payne:I think it's certainly opened the door to more and more screens. Maybe now we can do more ambitious types of screens where we use, for example, more than one fluorophore or more than one genotype at the same time, because the screening time is so much shorter and more efficient than you can introduce more variables.

About Dr. Elspeth Payne

Dr. Elspeth Payne is a senior clinical researcher/clinical consultant at the UCL Cancer Institute. Her laboratory at UCL's Cancer Institute is dedicated to studying inherited bone marrow failure diseases and leukemias and uses zebrafish to model these diseases. Dr. Payne is also a clinical hematologist at UCL Hospital, where she treats people with blood disorders such as leukemia and bone marrow failure.

About Dr. Alexandra Lubin

Dr. Lubin is a postdoctoral researcher at the UCL Cancer Institute, where she uses zebrafish to study myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) to develop novel therapeutic treatments. She previously completed her PhD in Chemical Biology at Imperial College London after studying chemistry at the University of Cambridge.

About IDEA Bio-Medical Ltd.

IDEA Bio-Medical a company specializing in automated microscopy and image analysis for life science researchers. It was founded in 2007 through a partnership between YEDA (the commercialization arm of the Weizmann Institute) and IDEA Machine Development (an innovation center). IDEA's products, the Hermes imaging system and the Athena image analysis software, have contributed to over 100 scientific publications in peer-reviewed journals and have made a significant impact on science worldwide.

IDEA Bio-Medical is currently focused on empowering zebrafish researchers, providing them with a reliable, robust solution for automated and unbiased image analysis of zebrafish by applying the company's knowledge and expertise.

To this end, IDEA developed a novel deep learning-based image analysis software for in vivo zebrafish experiments. The software automatically detects the zebrafish contour and its internal organs in bright field without requiring user input. The identified anatomy is coupled to fluorescence channels to enable anatomy-specific examination of fluorescence changes. It is an affordable, user-friendly system specifically designed for reliable, automated image-based analysis of zebrafish.

The softwareis available as a standalone productand accepts microscopy images in multiple image formats, including proprietary. Itis suitable for researchers imaging and analyzing just a handful of fish per week, as well as researchers imaging hundreds and thousands of fish in multi-well plates for large-scale displays. IDEA Bio-Medical offers a novel pay-per-use model for access to the software to enable flexible access.Therefore, any researchers using manual microscopes or third-party automated systems can easily use IDEA's Zfish software to extract quantitative, meaningful information from their zebrafish images on demand.

Contact IDEA Bio-Medical on our website Contact form and more information can be found in the zebrafish analysis software Product page.

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