High Content Screening Improves Pipelines, Advances Drug Discovery

               

From Screening Drug Compounds to Better Understanding Disease, Image-based HCS Maximizes Value of Data

Extracting Maximum Value from Phenotypic HCS Data

It’s well known that if you’re going to fail in drug discovery, it’s best to do it early. No one wants to waste energy, effort, and – more importantly – time and money taking a compound to clinical trials, only to see it fail...late in the process and at great cost. For a more productive discovery pipeline, image-based high content screening (HCS) is one phenotypic drug discovery strategy that maximizes data value.

According to Nature, phenotypic screening is a strategy for the identification of molecules with particular biological effects in cell-based assays or animal models. The technique gives researchers data on hundreds of parameters – over hundreds of wells and hundreds of plates. Unlike target-based approaches, phenotypic imaged-based screens without a known target offer a “boundless number of opportunities when it comes to what the numbers will tell you,” says Dr. Philip Gribbon of the Fraunhofer Institute.

The goal in phenotypic screening is the detailed multiparametric characterization of the cellular phenotype. It’s important to capture all the information the cell is providing, rather than single parameters. With comprehensive phenotypic information, the proper tools can help you derive actionable biological conclusions.

Using physiologically relevant model systems and leveraging rich information from image-based, high content screens – at the beginning of compound testing – helps discerns those phenotypic changes that are present without undesirable effects on the system of interest.

We know that phenotypic screening strategies were more productive than target-based drug discovery strategies in discovering first-in-class small molecule drugs, from 1999 to 2008. So while it’s not a new technology, phenotypic screening is enjoying renewed attention. 

Reaching HCS’s Full Potential

In a 2014 Journal of Biomolecular Screening article (Increasing the Content of High-Content Screening: An Overview) authors Shantu Singh, Anne E. Carpenter, and Auguste Genovesio “assess whether HCS is as high content as it can be.” They found the vast majority (60-80 percent) of HCS used univariate analysis tools and only one or two image-based features in the analysis. A continuing need for better analytical approaches was needed, they said, but concluded: “As data analysis approaches for these more complex types of HCS experiments become well developed and incorporated into easy-to-use software, we anticipate more powerful applications of HCS to blossom, the value of a typical experiment to increase, and ultimately the technology to be more widely adopted.”

That was music to our ears, coming at a time when we introduced High Content Profiler™, specifically to address the needs for a more robust, interactive, easy-to-use, fast, and powerful solution to analyze HCS images. Singh, et al, argued that “Advanced data analysis methods that enable full multiparametric data to be harvested for entire cell populations will enable HCS to finally reach its potential.”

So How Can You Reach Your Full Potential in Phenotypic HCS?

If you’re looking to complement your target-based drug discovery with phenotypic screening and image analysis, make sure you’ve got the best solutions – namely, no-compromise speed and sensitivity instruments, and the ability to manage, analyze, and visualize the mass of data from such screening.

For immediate phenotypic validation of your hits, you want:

• higher-throughput, extremely sensitive imaging

• automatic image transfer and powerful image segmentation and analysis

• advanced statistics, machine learning, and data analysis methods

From image acquisition to hit selection, PerkinElmer’s uniquely comprehensive phenotypic screening solutions help you generate rich, multi-parametric data with integrated downstream analysis, leading to better hypothesis generation and validation. In this brief video, customers discuss some of the advantages they’ve found using our HCS systems and informatics platforms to accelerate phenotypic screening workflows and better understand disease.

What you may not be aware of is a new version of High Content Profiler, still powered by TIBCO Spotfire®, addresses more than just HCS data; it covers a wide variety of analytical needs for high content analysis, including: 

• Drug profiling and clustering
• Cytometry analysis
• High throughput screening
• Curve fitting
• High dimensional data analysis

If your target-based approach isn’t delivering the results you need, you may want to consider phenotypic HCS. The technologies available today to capture stunning images and multiparametric data from each cell give you far more options to pursue – and as Dr. Gribbon says, boundless opportunities. Today, we are far better equipped to gain significant insights from all the data produced by HCS – maximizing the value of that data.

The right tools make all the difference. As leaders in the field of HCS, PerkinElmer provides the most comprehensive selection of integrated solutions for successful phenotypic-based drug discovery.

Are you using target-based or phenotypic imaging-based drug discovery strategies? If you do, what tools are you using to maximize the impact of your drug discovery data?
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