Not Just a Sum? Identifying Different Types of Interplay between Constituents in Combined Interventions.

<h4>Motivation</h4>Experiments in which the effect of combined manipulations is compared with the effects of their pure constituents have received a great deal of attention. Examples include the study of combination therapies and the comparison of double and single knockout model organis...

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Main Authors: Katrijn Van Deun, Lieven Thorrez, Robert A van den Berg, Age K Smilde, Iven Van Mechelen
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0125334
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author Katrijn Van Deun
Lieven Thorrez
Robert A van den Berg
Age K Smilde
Iven Van Mechelen
author_facet Katrijn Van Deun
Lieven Thorrez
Robert A van den Berg
Age K Smilde
Iven Van Mechelen
author_sort Katrijn Van Deun
collection DOAJ
description <h4>Motivation</h4>Experiments in which the effect of combined manipulations is compared with the effects of their pure constituents have received a great deal of attention. Examples include the study of combination therapies and the comparison of double and single knockout model organisms. Often the effect of the combined manipulation is not a mere addition of the effects of its constituents, with quite different forms of interplay between the constituents being possible. Yet, a well-formalized taxonomy of possible forms of interplay is lacking, let alone a statistical methodology to test for their presence in empirical data.<h4>Results</h4>Starting from a taxonomy of a broad range of forms of interplay between constituents of a combined manipulation, we propose a sound statistical hypothesis testing framework to test for the presence of each particular form of interplay. We illustrate the framework with analyses of public gene expression data on the combined treatment of dendritic cells with curdlan and GM-CSF and show that these lead to valuable insights into the mode of action of the constituent treatments and their combination.<h4>Availability and implementation</h4>R code implementing the statistical testing procedure for microarray gene expression data is available as supplementary material. The data are available from the Gene Expression Omnibus with accession number GSE32986.
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spelling doaj.art-08d8cf95b2154f76abe1df03c17bdf4e2022-12-21T23:31:54ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01105e012533410.1371/journal.pone.0125334Not Just a Sum? Identifying Different Types of Interplay between Constituents in Combined Interventions.Katrijn Van DeunLieven ThorrezRobert A van den BergAge K SmildeIven Van Mechelen<h4>Motivation</h4>Experiments in which the effect of combined manipulations is compared with the effects of their pure constituents have received a great deal of attention. Examples include the study of combination therapies and the comparison of double and single knockout model organisms. Often the effect of the combined manipulation is not a mere addition of the effects of its constituents, with quite different forms of interplay between the constituents being possible. Yet, a well-formalized taxonomy of possible forms of interplay is lacking, let alone a statistical methodology to test for their presence in empirical data.<h4>Results</h4>Starting from a taxonomy of a broad range of forms of interplay between constituents of a combined manipulation, we propose a sound statistical hypothesis testing framework to test for the presence of each particular form of interplay. We illustrate the framework with analyses of public gene expression data on the combined treatment of dendritic cells with curdlan and GM-CSF and show that these lead to valuable insights into the mode of action of the constituent treatments and their combination.<h4>Availability and implementation</h4>R code implementing the statistical testing procedure for microarray gene expression data is available as supplementary material. The data are available from the Gene Expression Omnibus with accession number GSE32986.https://doi.org/10.1371/journal.pone.0125334
spellingShingle Katrijn Van Deun
Lieven Thorrez
Robert A van den Berg
Age K Smilde
Iven Van Mechelen
Not Just a Sum? Identifying Different Types of Interplay between Constituents in Combined Interventions.
PLoS ONE
title Not Just a Sum? Identifying Different Types of Interplay between Constituents in Combined Interventions.
title_full Not Just a Sum? Identifying Different Types of Interplay between Constituents in Combined Interventions.
title_fullStr Not Just a Sum? Identifying Different Types of Interplay between Constituents in Combined Interventions.
title_full_unstemmed Not Just a Sum? Identifying Different Types of Interplay between Constituents in Combined Interventions.
title_short Not Just a Sum? Identifying Different Types of Interplay between Constituents in Combined Interventions.
title_sort not just a sum identifying different types of interplay between constituents in combined interventions
url https://doi.org/10.1371/journal.pone.0125334
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