The distribution of standard deviations applied to high throughput screening

Hanley, QS ORCID: https://orcid.org/0000-0002-8189-9550, 2019. The distribution of standard deviations applied to high throughput screening. Scientific Reports, 9: 1268. ISSN 2045-2322

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Abstract

High throughput screening (HTS) assesses compound libraries for “activity” using target assays. A subset of HTS data contains a large number of sample measurements replicated a small number of times providing an opportunity to introduce the distribution of standard deviations (DSD). Applying the DSD to some HTS data sets revealed signs of bias in some of the data and discovered a sub-population of compounds exhibiting high variability which may be difficult to screen. In the data examined, 21% of 1189 such compounds were pan-assay interference compounds. This proportion reached 57% for the most closely related compounds within the sub-population. Using the DSD, large HTS data sets can be modelled in many cases as two distributions: a large group of nearly normally distributed “inactive” compounds and a residual distribution of “active” compounds. The latter were not normally distributed, overlapped inactive distributions – on both sides –, and were larger than typically assumed. As such, a large number of compounds are being misclassified as “inactive” or are invisible to current methods which could become the next generation of drugs. Although applied here to HTS, it is applicable to data sets with a large number of samples measured a small number of times.

Item Type:	Journal article
Publication Title:	Scientific Reports
Creators:	Hanley, Q.S.
Publisher:	Nature Publishing Group
Date:	4 February 2019
Volume:	9
ISSN:	2045-2322
Identifiers:	Number Type 10.1038/s41598-018-36722-4 DOI
Divisions:	Schools > School of Science and Technology
Record created by:	Jonathan Gallacher
Date Added:	05 Dec 2018 14:29
Last Modified:	12 Mar 2019 13:31
URI:	https://irep.ntu.ac.uk/id/eprint/35241

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