HTS-Corrector: software for the statistical analysis and correction of experimental high-throughput screening data

Abstract

This paper describes HTS-Corrector, a software application for the analysis of HTS data, detection and visualization of systematic error, and corresponding correction of HTS signals. Three new methods for the statistical analysis and correction of raw HTS data are included in HTS-Corrector: background evaluation, well correction and hit-sigma distribution procedures intended to minimize the impact of systematic errors. We discuss the main features of HTS-Corrector and demonstrate the benefits of the algorithms.

An Automated High Throughput Screening-Compatible Assay to Identify Regulators of Stem Cell Neural Differentiation

“…Row data were analyzed and processed using both a custom Excel Worksheet or the HTS Corrector software (http://www.info2.uqam.ca/*makarenv/HTS/home.php) [13] for: (i) normalization of experimental HTS data by plate (mean centering procedure); (ii) elimination of outliers from the computation; (iii) topological analysis of the background; (iv) Hit selection (by plate). The Z-factor was calculated as described [14].…”

“…Aliquots (5 ll) from a test library, containing LiCl (200 mM) in triplicate random positions, or from control library (with medium only), were added to cells 6 h after automated seeding, and then re-added at every medium change until day 4. At 12 dpp, the fluorescence was measured and raw data processed by using the HTS-corrector software [13]. The upper graphics report the hit distribution by plate.…”

“…The compound addition tasks were scheduled from day 1 to 4 of neural differentiation, and aliquots of LiCl were added to get a final concentration of 10 mM. Fluorescence values were measured at day 12 of neural differentiation and raw data was analyzed by means of the HTS-corrector software, following standard procedures for plate-hit selection on an inhibitory assay [13]. As shown in Fig.…”

Arrayed cellular microenvironments for identifying culture and differentiation conditions for stem, primary and rare cell populations

“…An excellent review of the types of statistical analysis that can be applied to data generated from high-throughput screens is provided by Malo et al 18 . In addition, free software (HTSCorrector) for the analysis of high-throughput data has been developed by the same research group 19 . When using the ACME technology to identify potential hits, we use a z-score standardization method.…”

Using Clustering Techniques to Improve Hit Selection in High-Throughput Screening

“…Some statistical methods and software for correcting HTS data have been recently proposed in the literature. The reader is referred to the articles by Heuer et al, 1 Gunter et al, 2 Brideau et al, 3 Heyse, 4 Zhang et al, 5,6 Kevorkov and Makarenkov, 7 and Makarenkov et al 8,9 Another factor that influences the identification of active compounds is the hit selection procedure itself: Once the data are preprocessed and checked for quality, one has to decide which compounds should be tested in a secondary screen. However, from the statistical point of view, it is not well defined or reasonably grounded how to select the active compounds.…”