Biology subjects

Cabral-Marques, O.

Publications and source records attributed to Cabral-Marques, O..

4 recordsLinked to original sources

bioRxiv2026

From mice to humans: A multi-omic predictive framework for translational immunology

Mice are key preclinical animal models in vaccine and immunological research, yet their predictive value for human immunity remains contested. Here, we evaluated the translatability of murine models across inactivated and subunit vaccination (influenza, hepatitis B), acute infection (S. aureus, E. coli), and injury (burns and trauma), integrating transcriptomic profiles with sequence evolution, cis-regulatory architecture, and functional annotation. Functional modules were more conserved between species than individual orthologous genes. Translational accuracy depended on stimulus intensity, as infections and injuries engaged conserved signatures, while single-dose vaccination diverged. We then built multilayer models to predict human expression rank and direction of change, and to classify shared leading-edge genes. Adding evolutionary and regulatory layers improved these predictions. We provide a step-by-step R Markdown notebook to apply the models to user data. The study code and datasets are available at https://github.com/wapsyed/mousetohuman_multilayer

bioinformatics↗

bioRxiv2024

Dysregulation of synaptic-related genes within neuroimmune networks of peripheral blood mononuclear cells in major depressive disorder

Major depressive disorder (MDD) involves complex neuroimmune interactions linked to gene modulation. Our study investigates synaptic-related gene dysregulation in peripheral blood mononuclear cells (PBMCs) from MDD patients, showing how these immune cells mirror neural processes. Using RNA-seq data, we identified 1,383 differentially expressed genes (DEGs) related to neuroimmune crosstalk, with 49 DEGs effectively distinguishing MDD patients from controls based on synaptic functions. Synaptic genes, enriched for roles like vesicle transport, suggest mechanistic links between immune cells and neural signaling. Eleven synaptic-related DEGs were shared between PBMCs and brain regions involved in mood regulation, highlighting a common molecular signature. Among them, ADORA3 and RPS28 emerged as potential biomarkers. These findings highlight the potential of PBMCs in the diagnosis and treatment of MDD, reinforcing the development of future neuroimmune-targeted therapies for depression.

bioinformatics↗

bioRxiv2024

Integrative systems neuroimmunology reveals leukocyte-expressing PAX6 as a critical predictor of major depressive disorder

Major depressive disorder (MDD) is a complex psychiatric condition with a significant global impact. This study applied a genomic-driven integrative systems neuroimmunology approach to analyze transcriptomic data from 3,114 individuals (1,877 MDD patients and 1,237 controls). The analysis revealed neuroimmunological transcriptomic alterations, indicating cross-talk between the immune and nervous systems in peripheral blood mononuclear cells (PBMCs) and specific brain regions. Among 31 shared genes, NEGR1, PPP6C, SORCS3, and PAX6 emerged as significant predictors of MDD in patients PBMCs. Notably, PAX6 was also identified as a differentially expressed gene (DEG) in the amygdala, while NEGR1, PPP6C, and SORCS3 showed no significant differential expression in other central nervous system (CNS) regions. Validation by immunophenotyping in a mouse model of chronic stress demonstrated increased PAX6 expression in PBMCs, a gene previously associated with MDD in GWAS studies. Collectively, our findings suggest the existence of shared transcriptomic modules across the brain and immune system, highlighting PAX6 as a potential therapeutic target in MDD.

systems biology↗

bioRxiv2023

Muscle cell atrophy induced by miR-155-5p reveals molecular targets in skeletal muscle disorders

MicroRNAs are small regulatory molecules that control gene expression. An emerging property of muscle miRNAs is the cooperative regulation of transcriptional and epitranscriptional events controlling muscle phenotype. miR-155 has been related to muscular dystrophy and muscle cell atrophy. However, the function of miR-155 and its molecular targets in muscular dystrophies remain poorly understood. Through in silico and in vitro approaches we identify distinct transcriptional profile of muscle cell atrophy induced by miR-155-5p. The atrophic myotubes changed the expression of 359 genes (166 up-regulated and 193 down-regulated). We reanalyzed muscle transcriptomic data from dystrophin-deficient patients and detected overlap with gene expression patterns in miR-155-treated myotubes. Our analysis indicated that miR-155 regulates a set of transcripts, including Aldh1l, Nek2, Bub1b, Ramp3, Slc16a4, Plce1, Dync1i1, and Nr1h3. Enrichment analysis demonstrates 20 targets involved in metabolism, cell cycle regulation, muscle cell maintenance, and immune system. Moreover, digital cytometry confirmed a significant increase in M2 macrophages, indicating miR-155 effects on immune response in dystrophic muscles. We highlight a critical miR-155 associated with disease-related pathways in skeletal muscle disorders.

genomics↗