Getting a handle on screen design in complex biological systems: SLAS2018 track

By Simon Fogarty

Designing an effective biological screen is always a case of knowing when to quit versus when to keep going, so you don’t miss potentially important factors. When working with complex biological systems, rational screen design becomes even more of a challenge. A main presentation track at SLAS 2018 will focus on that question. Entitled "Assay Development and Screening", the track will include a number of relevant sessions, including "Screening to Optimize Chemical and Biological Space," chaired by Fred King, Ph.D., Genomics Institute of the Novartis Research Foundation. We spoke to Dr. King to learn more.

The session will focus on strategies to help keep the size of a screen "reasonable" while still making it possible to obtain high-quality leads, says Dr. King. "Different labs have different views on what should be considered as a reasonable-sized screen. However, given the tremendous number of variables that could be addressed during an assay, there is universal appreciation for the necessity to deprioritize certain aspects of a screen design."

Don't overstuff it: Knowing how much is too much is important for an effective biological screen design.

Narrowing the selections

The choices to be made in deciding what variables to prioritize and what aspects of a screen to deemphasize are fairly subjective. Consequently, every screening campaign is filled with uncertainty as to whether key findings may be missed with the chosen workflow design.

"The invited speakers will provide thought-provoking insights into strategies and technologies used by experts in the field to maximize the information obtained for a given screen size," Dr. King says.

The area of rational screen design is a timely and broadly relevant topic. Included in the session will be discussions of which small molecules, biologics, etc., should be investigated during a screen. The presentations will focus on the design of compound sets that have been enriched for characterized biological activity (including cellular mechanism of action) along with chemical diversity.

Raman spectroscopy promises results

Approaches related to assay design that minimize false positives will also be described. For characterizing biologic samples, one approach involves leveraging Raman spectroscopy. "This is a technique that SLAS2108 attendees should keep an eye on," says Dr. King. "At present, systems are fairly low throughput, but as the field progresses, Raman spectroscopy could be used to confirm that you are screening what you think you are screening."

Session presentations include:

• Complex assays for complex targets: Next-gen oncology drug discovery (Novartis Institute for Biomedical Research)
• Designed diversity and bioannotated compound libraries for obtaining maximal value from screens in induced pluripotent stem cell-derived cells and other complex biological systems (Evotec AG)
• Application of a robustness set to guide the development of 1536-well format assays for HTS (Pivot Park Screening Center BV)
• Label-free Raman spectroscopy for rapid identification of biologics (Johns Hopkins University)

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Dr. Fred King
Acknowledgement