ESKAPE Act Plus: Pathway Activation Analysis for Bacterial Pathogens

The last 20 years have witnessed an explosion in publicly available gene expression and proteomic data and new tools to help researchers analyze these data. Tools typically include statistical approaches to identify differential expression, integrate prior knowledge, visualize results, and suggest how differential expression relates to changes in phenotype. Here, we provide a simple web-based tool that bridges some of the gaps between the functionality available to those studying eukaryotes and those studying prokaryotes. Specifically, our Shiny web application ESKAPE Act PLUS allows researchers to upload results of high-throughput bacterial gene or protein expression experiments from 13 species, including the six ESKAPE pathogens, to our system and receive (i) an analysis of which KEGG pathways or GO terms are significantly activated or repressed, (ii) visual representations of the magnitude of activation or repression in each category, and (iii) detailed diagrams showing known relationships between genes in each regulated KEGG pathway and fold changes of individual genes. Importantly, our statistical approach does not require users to identify which genes or proteins are differentially expressed. ESKAPE Act PLUS provides high-quality statistics and graphical representations not available using other web-based systems to assess whether prokaryotic biological functions are activated or repressed by experimental conditions. To our knowledge, ESKAPE Act PLUS is the first application that provides pathway activation analysis and pathway-level visualization of gene or protein expression for prokaryotes. IMPORTANCE ESKAPE pathogens are bacteria of concern because they develop antibiotic resistance and can cause life-threatening infections, particularly in more susceptible immunocompromised people. ESKAPE Act PLUS is a user-friendly web application that will advance research on ESKAPE and other pathogens commonly studied by the biomedical community by allowing scientists to infer biological phenotypes from the results from high-throughput bacterial gene or protein expression experiments. ESKAPE Act PLUS currently supports analysis of 23 strains of bacteria from 13 species and can also be used to re-analyze publicly available data to generate new findings and hypotheses for follow-up experiments.