Trust but verify
There is an article in Nature describing a collection of problems that have arisen from incorrect chemical structures in biological screens DOI. I'm slightly surprised that this is regarded as newsworthy, but I guess it serves as a timely reminder.
The data from screening campaigns invariably contains errors
- It is often a single point assay
- Quality and diversity of Sample Collection is variable
- Compounds may interfere with the detection system
- False positives due to aggregation
- High density plates can result in cross contamination, edge effects
There is a very simple mantra you should adopt when analysing screening data "Trust but verify".
- Check compounds that were found active against the selected target are re-tested using the same assay conditions used during the HTS.
- Does a resynthesised (not repurchased) show the same activity
- Dose response curve generation: an IC50 or EC50 value is then generated, does it have a reasonable slope? Uneffected by incubation time.
- Are related analogues available, check for genuine Structure-Activity Relationships
There is a strategy for the analysis of HTS data in the Drug Discovery Resources.