Biology subjects

Farinas, M.

Publications and source records attributed to Farinas, M..

3 recordsLinked to original sources

bioRxiv2026

TRAFIKK: systematic prediction and mechanistic interpretation of anticancer drug synergies

Effective drug combination therapies can improve cancer treatment, yet the mechanistic basis of drug synergy remains poorly understood. Most computational approaches prioritize predictive accuracy over molecular mechanistic interpretability, providing hence limited insights into how synergistic effects emerge across signalling contexts. We developed Trafikk, a molecular-signalling network-based framework that simulates drug perturbations in cell line-specific computational models to mirror functional outcomes in experimental combination screens. Across two independent large-scale datasets, Trafikk identified synergistic combinations with >77% recall. Functional response predictions revealed both conserved and context-dependent mechanisms. While AKT-MEK co-inhibition consistently disrupted coordinated survival and apoptotic signalling in 742 cell lines, PI3K-BCL2 synergy arose through distinct death programs shaped by cell-context-specific network constraints. Trafikk combines predictive performance with mechanistic interpretability, capturing how and why drug synergy emerges across cellular contexts. Source code, installation instructions and usage tutorial are freely available at https://github.com/druglogics/trafikk. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=147 SRC="FIGDIR/small/723755v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@9f09f0org.highwire.dtl.DTLVardef@1456ef5org.highwire.dtl.DTLVardef@177b11forg.highwire.dtl.DTLVardef@10d7435_HPS_FORMAT_FIGEXP M_FIG C_FIG

systems biology↗

bioRxiv2025

BooLEVARD: Boolean Logical Evaluation of Activation and Repression in Directed pathways

Boolean models are widely used for studying dynamic processes of biological systems. However, their inherent discrete nature limits their ability to capture continuous aspects of signal transduction, such as signal strength or protein activation levels. Although existing tools provide some path exploration capabilities that can be used to explore signal transduction circuits, the computational workload often requires simplifying assumptions that compromise the accuracy of the analysis. Here, we introduce BooLEVARD, a Python package designed to efficiently quantify the number of paths leading either to node activation or repression in Boolean models, which offers a more detailed and quantitative perspective on how molecular signals propagate through signaling networks. By focusing on the collection of non-redundant paths directly influencing Boolean outcomes, BooLEVARD enhances the precision of signal strength representation. We showcase the application of BooLEVARD in studying cell-fate decisions using a Boolean model of cancer metastasis, demonstrating its ability to identify critical signaling events. Furthermore, BooLEVARD provides a refined understanding of signaling dynamics, which can increase our understanding of disease development and drug responses. BooLEVARD is freely available at https://github.com/farinasm/boolevard.

systems biology↗

bioRxiv2021

SARS-CoV-2 RBD-Tetanus toxoid conjugate vaccine induces a strong neutralizing immunity in preclinical studies

Controlling the global COVID-19 pandemic depends, among other measures, on developing preventive vaccines at an unprecedented pace. Vaccines approved for use and those in development intend to use neutralizing antibodies to block viral sites binding to the hosts cellular receptors. Virus infection is mediated by the spike glycoprotein trimer on the virion surface via its receptor binding domain (RBD). Antibody response to this domain is an important outcome of the immunization and correlates well with viral neutralization. Here we show that macromolecular constructs with recombinant RBD conjugated to tetanus toxoid induce a potent immune response in laboratory animals. Some advantages of the immunization with the viral antigen coupled to tetanus toxoid have become evident such as predominant IgG immune response due to affinity maturation and long-term specific B-memory cells. This paper demonstrates that subunit conjugate vaccines can be an alternative for COVID-19, paving the way for other viral conjugate vaccines based on the use of small viral proteins involved in the infection process.

immunology↗