Traditional HTS approach is typically a sequential and iterative process starting with a full library screen, followed by dose-response and counter screen(s), and multiple rounds of hit-to-lead activity. It could take many months to make a lead determination.
At Boehringer, we are trying out an intensive parallel approach, where we apply a lot of resources upfront including assay development, screening (both of the general library and more focused libraries), virtual screening, and medicinal chemistry. Our screening, assay development, and chemistry groups work hand in hand during this process. The hope is to collapse the timeline and enable quicker lead decisions, says E. Michael August, Ph.D., senior principal scientist, biomolecular screening group at Boehringer Ingelheim Pharmaceuticals (www.boehringer-ingelheim.com).
As HTS throughput has increased, the volume, complexity of data, and the content level of information output, data processing has become harder and more time-intensive. It can take several days to sift through all this information in a conventional way, maintains Stephan Heyse, Ph.D., project head of screening informatics at Genedata (www.genedata.com).
The basic question a compound screen seeks to answer is: What are the true biological effects of a compound? The challenge for current data analysis tools is analyzing multiple readouts for signs of compound activity, specificity, and cross-reactivity to determine real effects from artifacts. An additional goal is to interpret compound effects from multiple assays that use diverse technologies to gain a comprehensive picture of a compounds mode-of-action.
Precision and accuracy in data interpretation are key factors in HTS. Genedata offers integrated solutions in a multistep workflow to enable customers to manage their throughput and the data analysis complexity of HTS, says Dr. Heyse.
The companys Genedata Screener enables the analysis of millions of data points and provides precise data that represents biological reality, he explains, noting that the product performs large-scale processing (>10,000 samples) of dose response curves and reduces the complexity in separating out true response from false positives.
Genedata Screener also performs high-level interpretation of high-content screens, such as cell-based assays, by aligning multiple test responses to provide a complete picture of compound activity, according to Dr. Heyse.