What is it about?
Dispensing processes profoundly influence estimates of biological activity of compounds. In this study using published inhibitor data for the tyrosine kinase EphB4, we show that IC50 values obtained via disposable tip-based serial dilution and dispensing versus acoustic dispensing differ by orders of magnitude with no correlation or ranking of datasets.
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Why is it important?
Traditional dispensing processes are another important source of error in high-throughput screening that impacts computational and statistical analyses. These findings have far-reaching implications in biological research and calls into question the quality of HTS data available in the public databases and certainly emphasizes the need for appropriate meta data to be available to ensure that it is known WHAT dispensing method was used to deliver the material during the assay measurement
Perspectives
When Joe first chatted with me about the patents he had found from AZ and what turned into this project, I had no idea what it would lead too. Its one of those cases were it not for the editorial / blog that brought us to his attention, this probably would never got done. Yes the dataset is limited, yes its only one target but still I think it proved a wake up call for everyone.
Dr Sean Ekins
Collaborations in Chemistry
Read the Original
This page is a summary of: Dispensing Processes Impact Apparent Biological Activity as Determined by Computational and Statistical Analyses, PLoS ONE, May 2013, PLOS,
DOI: 10.1371/journal.pone.0062325.
You can read the full text:
Resources
Making People Aware of Biological Data Limitations
A blog post on the Phoenix Next Inc. site by Sean Ekins, one of the authors of the paper
What data do we trust now in the world of high-throughput screening and public compound databases
A blog post by myself on the ChemConnector blog regarding general issues of data quality and how this relates to high-throughput screening data and public compound databases
In the Pipeline Blog from Derek Lowe: Drug Assay Numbers, All Over the Place
This blog post by Derek Lowe, who writes the In the Pipeline Blog, is best captured in terms of his opening sentence: "There's a truly disturbing paper out in PLoSONE with potential implications for a lot of assay data out there in the literature. "
Dispensing Processes Profoundly Impact Biological Assays and Computational and Statistical Analyses
SlideShare Presentation: Dispensing processes profoundly influence estimates of biological activity of compounds. In this study using published inhibitor data for the tyrosine kinase EphB4, we show that IC50 values obtained via disposable tip-based serial dilution and dispensing versus acoustic dispensing differ by orders of magnitude with no correlation or ranking of datasets.
Modeling a serial dilution experiment on different liquid handling/dispensing devices.
John Chodera from the Memorial Sloan-Kettering Cancer Center modeled one of the main features of the Echo. Its direct dispensing technology that allows a dilution series over several orders of magnitude in concentration to be created directly without the need for serial dilution. Could the observed discrepancy be explained by the difference in the accuracy with which a serial dilution can be created by these two technologies? His modeling work examines this question
Moving Liquids with Sound Helps Identify Drug Candidates that Traditional Lab Techniques Miss
A Drug Discovery Today Article reviewing our article and the questions "How do researchers know whether new molecules will have a positive or negative effect? How much does the technique for moving a liquid affect the results? What about testing compounds for their environmental or health impacts: Is one liquid handling process better than another when it comes to accuracy of the data? "
Pipettes and Serial Dilutions Have Dramatic Negative Effects on Biological Assays
A poster representation of our article delivered by Joe Olechno and reporting on liquid handling and dilution processes profoundly influencing estimates of biological activity. We compared tip-based serial dilution and dispensing versus acoustic dispensing with direct dilution.
How you move compounds may matter
A blog post by Sean Ekins on the Collaborative Drug Discovery website.
Quality Issues with Public Domain Chemogenomics Data
This mini-review discusses some of the most common issues with public domain biological data related to chemogenomic analysis. The errors in data can originate from problems with the experiments themselves and their interpretation, or from more mundane issues such as data extraction and annotation. These issues are not unique for a certain database but are shared by all the public domain databases and can plague commercial and in-house bioactivity databases as well.
Why High-Throughput Screening Data quality is important: Ephrin pharmacophores and statistical correlations
POSTER on Slideshare: Dispensing processes and the tools used have a profound influence on estimates of compound activity. Researchers have shown that leachates from plastic labware can profoundly affect biological assays. Data derived using disposable tip-based serial dilution and dispensing have shown a reduction in inhibition compared to acoustic dispensing with some compounds appearing hundreds of times more active with the acoustic process.
Faculty of 1000 (F1000) review
This is a review of our paper by Rafael Najmanovich in F1000
Contributors
The following have contributed to this page
