title: ROMA: Representation and Quantification of Module Activity from Target Expression Data.
abstract: In many analyses of high-throughput data in systems biology, there is a need to quantify the activity of a set of genes in individual samples. A typical example is the case where it is necessary to estimate the activity of a transcription factor (which is often not directly measurable) from the expression of its target genes. We present here ROMA (Representation and quantification Of Module Activities) Java software, designed for fast and robust computation of the activity of gene sets (or modules) with coordinated expression. ROMA activity quantification is based on the simplest uni-factor linear model of gene regulation that approximates the expression data of a gene set by its first principal component. The proposed algorithm implements novel functionalities: it provides several method modifications for principal components computation, including weighted, robust and centered methods; it distinguishes overdispersed modules (based on the variance explained by the first principal component) and coordinated modules (based on the significance of the spectral gap); finally, it computes statistical significance of the estimated module overdispersion or coordination. ROMA can be applied in many contexts, from estimating differential activities of transcriptional factors to finding overdispersed pathways in single-cell transcriptomics data. We describe here the principles of ROMA providing several practical examples of its use. ROMA source code is available at https://github.com/sysbio-curie/Roma.
authors.affiliation: Computational and Systems Biology of Cancer, Institut CurieParis, France; PSL Research UniversityParis, France; Institut National de la Santé et de la Recherche Médicale U900Paris, France; Mines ParisTechParis, France.
authors.forename: Loredana
authors.initials: L
authors.lastname: Martignetti
authors.affiliation: Computational and Systems Biology of Cancer, Institut CurieParis, France; PSL Research UniversityParis, France; Institut National de la Santé et de la Recherche Médicale U900Paris, France; Mines ParisTechParis, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Calzone
authors.affiliation: Computational and Systems Biology of Cancer, Institut CurieParis, France; PSL Research UniversityParis, France; Institut National de la Santé et de la Recherche Médicale U900Paris, France; Mines ParisTechParis, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Bonnet
authors.affiliation: Computational and Systems Biology of Cancer, Institut CurieParis, France; PSL Research UniversityParis, France; Institut National de la Santé et de la Recherche Médicale U900Paris, France; Mines ParisTechParis, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Barillot
authors.affiliation: Computational and Systems Biology of Cancer, Institut CurieParis, France; PSL Research UniversityParis, France; Institut National de la Santé et de la Recherche Médicale U900Paris, France; Mines ParisTechParis, France.
authors.forename: Andrei
authors.initials: A
authors.lastname: Zinovyev
keywords: coordinated pathway; gene expression; gene set; module activity; overdispersed pathway; proteomics; transcription factors