Transfer of regulatory knowledge from human to mouse for functional genomic analysis

Publication date: Available online 13 September 2019Source: Biochimica et Biophysica Acta (BBA) - Gene Regulatory MechanismsAuthor(s): Christian H. Holland, Bence Szalai, Julio Saez-RodriguezAbstractTranscriptome profiling followed by differential gene expression analysis often leads to lists of genes that are hard to analyze and interpret. Functional genomic tools are powerful approaches for downstream analysis, as they summarize the large and noisy gene expression space into a smaller number of biological meaningful features. In particular, methods that estimate the activity of processes by mapping transcripts level to process members are popular. However, footprints of either a pathway or transcription factor (TF) on gene expression show superior performance over mapping-based gene sets. These footprints are largely developed for humans and their usability in the broadly-used model organism Mus musculus is uncertain. Evolutionary conservation of the gene regulatory system suggests that footprints of human pathways and TFs can functionally characterize mice data. In this paper we analyze this hypothesis. We perform a comprehensive benchmark study exploiting two state-of-the-art footprint methods, DoRothEA and an extended version of PROGENy. These methods infer TF and pathway activity, respectively. Our results show that both can recover mouse perturbations, confirming our hypothesis that footprints are conserved between mice and humans. Subsequently, we illustrate the usabi...

Source: Biochimica et Biophysica Acta (BBA) Gene Regulatory Mechanisms - September 13, 2019 Category: Genetics & Stem Cells Source Type: research