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

J Biomol Screen. 2013 Apr;18(4):367-77. doi: 10.1177/1087057112469257. Epub 2012 Nov 29.

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.

MeSH terms

  • Computer Simulation
  • High-Throughput Screening Assays / methods*
  • Humans
  • Hydroxamic Acids / pharmacology
  • MCF-7 Cells
  • Principal Component Analysis
  • Statistics as Topic*

Substances

  • Hydroxamic Acids
  • trichostatin A