Biology subjects

Rougny, A.

Publications and source records attributed to Rougny, A..

3 recordsLinked to original sources

bioRxiv2020

Reusability and composability in process description maps: RAS-RAF-MEK-ERK signalling

Detailed maps of the molecular basis of the disease are powerful tools for interpreting data and building predictive models. Modularity and composability are considered necessary network features for large-scale collaborative efforts to build comprehensive molecular descriptions of disease mechanisms. An effective way to create and manage large systems is to compose multiple subsystems. Composable network components could effectively harness the contributions of many individuals and enable teams to seamlessly assemble many individual components into comprehensive maps. We examine manually-built versions of the RAS-RAF-MEK-ERK cascade from the Atlas of Cancer Signalling Network, PANTHER and Reactome databases and review them in terms of their reusability and composability for assembling new disease models. We identify design principles for managing complex systems that could make it easier for investigators to share and reuse network components. We demonstrate the main challenges including incompatible levels of detail and ambiguous representation of complexes and highlight the need to address these challenges.

systems biology↗

bioRxiv2020

A Detailed Map of Coupled Circadian Clock and Cell Cycle with Qualitative Dynamics Validation

The temporal coordination of biological processes by the circadian clock is an important mechanism, and its disruption has negative health outcomes, including cancer. Experimental and theoretical evidence suggests that the oscillators driving the circadian clock and the cell cycle are coupled through phase locking. We present a detailed and documented SBGN PD map of known mechanisms related to the regulation of the circadian clock, and its coupling with an existing cell cycle SBGN PD map which includes main interactions of the mammalian cell cycle. The coherence of the merged map has been validated with a qualitative dynamics analysis. We verified that the coupled circadian clock and cell cycle maps allow reproducing the observed sequence of phase markers. Moreover, we predicted mutations that contribute to regulating checkpoints of the two oscillators. Strikingly, our approach underlines the potential key role of the core clock protein NR1D1 in regulating cell cycle progression. We predicted that its activity influences negatively the progression of the cell cycle from phase G2 to M. It is consistent with the earlier experimental finding that pharmacological activation of NR1D1 inhibits tumour cell proliferation and shows that our approach can identify biologically relevant species in the context of large and complex networks.

systems biology↗

bioRxiv2020

SBGN Bricks Ontology as a tool to describe recurring concepts in molecular networks

A comprehensible representation of a molecular network is key to communicating and understanding scientific results in systems biology. The Systems Biology Graphical Notation (SBGN) has emerged as the main standard to represent such networks graphically. It has been implemented by different software tools, and is now largely used to communicate maps in scientific publications. However, learning the standard, and using it to build large maps, can be tedious. Moreover, SBGN maps are not grounded on a formal semantic layer and therefore do not enable formal analysis. Here, we introduce a new set of patterns representing recurring concepts encountered in molecular networks, called SBGN bricks. The bricks are structured in a new ontology, the BricKs Ontology (BKO), to define clear semantics for each of the biological concepts they represent. We show the usefulness of the bricks and BKO for both the template-based construction and the semantic annotation of molecular networks. The SBGN bricks and BKO can be freely explored and downloaded at sbgnbricks.org.

systems biology↗