BACKGROUND: Understanding the Mechanism of Action (MoA) of a compound is an often challenging but equally crucial aspect of drug discovery that can help improve both its efficacy and safety. Computational methods to aid MoA elucidation usually either aim to predict direct drug targets, or attempt to understand modulated downstream pathways or signalling proteins. Such methods usually require extensive coding experience and results are often optimised for further computational processing, making them difficult for wet-lab scientists to perform, interpret and draw hypotheses from. RESULTS: To address this issue, we in this work present MAVEN (Mechanism of Action Visualisation and Enrichment), an R/Shiny app which allows for GUI-based prediction of drug targets based on chemical structure, combined with causal reasoning based on causal protein-protein interactions and transcriptomic perturbation signatures. The app computes a systems-level view of the mechanism of action of the input compound. This is visualised as a sub-network linking predicted or known targets to modulated transcription factors via inferred signalling proteins. The tool includes a selection of MSigDB gene set collections to perform pathway enrichment on the resulting network, and also allows for custom gene sets to be uploaded by the researcher. MAVEN is hence a user-friendly, flexible tool for researchers without extensive bioinformatics or cheminformatics knowledge to generate interpretable hypotheses of compound Mechanism of Action. CONCLUSIONS: MAVEN is available as a fully open-source tool at https://github.com/laylagerami/MAVEN with options to install in a Docker or Singularity container. Full documentation, including a tutorial on example data, is available at https://laylagerami.github.io/MAVEN .

MOTIVATION: Omics data are broadly used to get a snapshot of the molecular status of cells. In particular, changes in omics can be used to estimate the activity of pathways, transcription factors and kinases based on known regulated targets, that we call footprints. Then the molecular paths driving these activities can be estimated using causal reasoning on large signalling networks. RESULTS: We have developed FUNKI, a FUNctional toolKIt for footprint analysis. It provides a user-friendly interface for an easy and fast analysis of transcriptomics, phosphoproteomics and metabolomics data, either from bulk or single-cell experiments. FUNKI also features different options to visualize the results and run post-analyses, and is mirrored as a scripted version in R. AVAILABILITY AND IMPLEMENTATION: FUNKI is a free and open-source application built on R and Shiny, available at https://github.com/saezlab/ShinyFUNKI and https://saezlab.shinyapps.io/funki/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

The complex dynamics of biological systems is primarily driven by molecular interactions that underpin the regulatory networks of cells. These networks typically contain positive and negative feedback loops, which are responsible for switch-like and oscillatory dynamics, respectively. Many computing systems rely on switches and clocks as computational modules. While the combination of such modules in biological systems leads to a variety of dynamical behaviours, it is also driving development of new computing algorithms. Here we present a historical perspective on computation by biological systems, with a focus on switches and clocks, and discuss parallels between biology and computing. We also outline our vision for the future of biological computing.

Biological systems are adapted to respond quickly to changes in their environment. Signal processing often leads to all-or-none switch-like activation of downstream pathways. Such biological switches are based on molecular interactions that form positive feedback loops. Proper signal processing and switching have to be made by the noisy interactions of fluctuating molecular components; still, switching has to happen quickly once a threshold in the input signal is reached. Several computing algorithms have been designed to perform similar all-or-none decisions with high efficiency. We discuss here how the structure and dynamical features of a computational algorithm resemble the behaviour of a large class of biological switches and what makes them work efficiently. Furthermore, we highlight what biologists can learn by looking at specific features of computational algorithms.