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The multidimensional perturbation value: A single metric to measure similarity and activity of treatments in high-throughput multidimensional screens

Hutz, Janna and Nelson, Thomas and Wu, Hua and Mcallister, Gregory and Moutsatsos, Ioannis and Jaeger, Savina and Bandyopadhyay, Somnath and Nigsch, Florian and Cornett, Allen and Jenkins, Jeremy and Selinger, Douglas (2013) The multidimensional perturbation value: A single metric to measure similarity and activity of treatments in high-throughput multidimensional screens. Journal of Biomolecular Screening, 18 (4). pp. 367-377. ISSN 1087-0571; 1552-454X

Abstract

Screens using high-throughput, information-rich technologies such as microarrays, high-content screening (HCS), and next-generation sequencing (NGS) have become increasingly widespread. Compared with single-readout assays, these methods produce a more comprehensive picture of the effects of screened treatments. However, interpreting such multidimensional readouts is challenging. Univariate statistics such as t-tests and Z-factors cannot easily be applied to multidimensional profiles, leaving no obvious way to answer common screening questions such as "Is treatment X active in this assay?" and "Is treatment X different from (or equivalent to) treatment Y?" We have developed a simple, straightforward metric, the multidimensional perturbation value (mp-value), which can be used to answer these questions. Here, we demonstrate application of the mp-value to three data sets: a multiplexed gene expression screen of compounds and genomic reagents, a microarray-based gene expression screen of compounds, and an HCS compound screen. In all data sets, active treatments were successfully identified using the mp-value, and simulations and follow-up analyses supported the mp-value's statistical and biological validity. We believe the mp-value represents a promising way to simplify the analysis of multidimensional data while taking full advantage of its richness. © 2012 Society for Laboratory Automation and Screening.

Item Type: Article
Additional Information: Unmapped bibliographic data: LA - English [Field not mapped to EPrints] ST - The multidimensional perturbation value: A single metric to measure similarity and activity of treatments in high-throughput multidimensional screens [Field not mapped to EPrints] AU - Hutz, J. E. [Field not mapped to EPrints] AU - Nelson, T. [Field not mapped to EPrints] AU - Wu, H. [Field not mapped to EPrints] AU - McAllister, G. [Field not mapped to EPrints] AU - Moutsatsos, I. [Field not mapped to EPrints] AU - Jaeger, S. A. [Field not mapped to EPrints] AU - Bandyopadhyay, S. [Field not mapped to EPrints] AU - Nigsch, F. [Field not mapped to EPrints] AU - Cornett, B. [Field not mapped to EPrints] AU - Jenkins, J. L. [Field not mapped to EPrints] AU - Selinger, D. W. [Field not mapped to EPrints] AD - (Hutz, Nelson, Wu, McAllister, Moutsatsos, Jaeger, Cornett, Jenkins, Selinger) Developmental and Molecular Pathways, Novartis Institutes for Biomedical Research, 250 Massachusetts Ave., Cambridge, MA 02139, United States [Field not mapped to EPrints] DB - Embase [Field not mapped to EPrints] DP - Ovid Technologies [Field not mapped to EPrints] AN - 2013213324 [Field not mapped to EPrints]
Keywords: high-content screening
Date Deposited: 01 Feb 2017 00:45
Last Modified: 01 Feb 2017 00:45
URI: https://oak.novartis.com/id/eprint/7566

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