Biological networks such as protein-protein interaction networks or gene regulatory networks are an integral part to understand biological systems. They are powerful means to integrate a multitude of biological and experimental information. We work with temporality of networks, and focus on complex networks and knowledge graphs to understand biological phenomena and diseases.
The four phases and essential check points of the cell cycle
Extraction of cell cycle phases from the higher-order network
Many biological systems go through various phases, or states, over different time and space scales. These phases, and their order in time, are often crucial to the functioning of these systems and even determine their evolution/fate. To understand or even predict these phases would yield crucial insight into the temporal organisation of such systems, and ultimately, into their evolution.
The cell cycle, at the heart of all biological development, illustrates this well. Indeed, in order to eventually divide into two cells, the cell typically progresses through 4 macroscopic phases. At the microscopic level, these phases are driven by protein-protein interactions (PPIs).
To investigate the temporal organisation of the cell cycle, however, the typical static PPI network is not enough. That is why we build a temporal PPI network, by integrating time series of protein concentrations to the static one. By doing so, we open the whole toolbox of temporal network and higher-order networks to study our biological system.
Check out Phasik, as a software to model temporality in a complex network.
Check out the paper on Phasik: Lucas, et al., Cell Report Methods 2023, doi: 10.1016/j.crmeth.2023.100397
TimeNexus projects temporal data on the layers of a multilayer network.
Biological networks are not static, but dynamic. With the availability of time-series datasets, we can follow the dynamics of expression changes - on protein or RNA level - experimentally. To integrate these types of data with biological networks is currently not so easy, as few ready-to-use tools exist. In order to address this gap, we have developed the Cytoscape app TimeNexus. In TimeNexus, we project temporal data on a multilayer network: each layer represents one time-point. We refer to these networks as 'temporal multilayer networks (tMLNs). With TimeNexus, a user can easily create such a tMLN simply by providing tabular information on the network itself, as well as the temporal layers in form of time-series data. TimeNexus furthermore provides a framework for visualizing a tMLN, as well as for extracting active subnetworks using the Cytoscape apps PathLinker and the ANAT server.
Check out the TimeNexus paper: Pierrelee, et al., Sci Rep 2021, 10.1038/s41598-021-93128-5
You can also download the TimeNexus app directly from the Cytoscape App store.
This project was done in close collaboration with Laurent Tichit (I2M). It was funded by a shared ANR grant our team has with Aziz Moqrich (IBDM), 'MYOCHRONIC'.
Previous work done in network biology for interpretation and integration of data coming from -omics studies:
1) miMerge and miScore for the generation of non-redundant protein interaction networks (Villaveces, et al., Database, 2015, doi: 10.1093/database/bau131)
2) KEGGViewer (Villaveces, et al., F1000Res 3:43, 2014, doi: 10.12688/f1000research.3-43.v1) for the visualization and integration of pathway data; and PsiquicGraph (Villaveces, et al., F1000Res 3:44, 2014, doi: 10.12688/f1000research.3-44.v1) both available via the BioJS platform;
3) the Cytoscape plugins viPEr for generating focus networks based on -omics data and PEANUT for pathway enrichment of focus networks (Garmhausen et al., BMC Genomics 16:790, 2015, doi: 10.1186/s12864-015-2017-z).