Biology subjects

Couto, B.

Publications and source records attributed to Couto, B..

3 recordsLinked to original sources

bioRxiv2026

Revisiting Logistic Regression for High-Dimensional Gene Expression Data

Logistic regression remains a widely used classification method due to its interpretability and computational efficiency, but its direct application to high-dimensional biomedical data is limited when the number of features greatly exceeds the number of samples. In this paper, we propose a reformulated logistic regression framework designed for feature selection and classification in complex high-dimensional settings. The method is evaluated on three biomedical datasets, including scenarios with tens of thousands of attributes and substantially fewer samples. Across these datasets, the proposed approach achieved clear separation between control and disease groups while selecting a compact set of features. Several selected features were consistent with previously reported disease-associated markers, supporting the biological plausibility of the model, while additional selected features suggest potential novel candidates for further investigation. These results indicate that the proposed framework may provide an interpretable and computationally efficient alternative for feature selection in high-dimensional computational biology applications.

bioinformatics↗

bioRxiv2026

Disrupted Higher-Order Topology in OCD Brain Networks Revealed by Hodge Laplacian - an ENIGMA Study

Brain disorders are increasingly understood as disorders of distributed brain circuits, yet functional connectivity (FC), the dominant framework for mapping them, treats the brain as a collection of pairwise relationships between regions and cannot represent pathology distributed across coordinated sets of connections. We introduce a Hodge-Laplacian topological framework that localizes higher-order "loop" (1-cycle) organization within functional connectome, maps each loop to specific edges and networks, and yields a subject-level measure of loop expression. Applied to resting-state fMRI from the ENIGMA-OCD consortium (1,024 patients and 1,028 controls across 28 sites), the framework identified 93 loop-level abnormalities in obsessive-compulsive disorder (OCD), concentrated in frontoparietal and somatomotor systems. The edges forming these loops largely showed no significant differences between groups, indicating that the abnormalities were invisible to conventional FC analysis. The frontoparietal and somatomotor loop clusters recurred across the clinical subgroups, suggesting convergence on a shared higher-order phenotype. Robustness analyses showed the loop signal reflected higher-order organization rather than an artifact of individual edges, the network backbone, or any single site. These results indicate that coordinated, multi-edge pathology exists and can be localized even when pairwise analyses fail to detect it, positioning higher-order topology as a generalizable axis for mapping circuit pathology across psychiatric and neurological disorders.

neuroscience↗

bioRxiv2023

4R-Tau seeding activity unravels molecular subtypes in patients with Progressive Supranuclear Palsy

Progressive Supranuclear palsy (PSP) is a 4-repeat (4-R) tauopathy. We hypothesized that the molecular diversity of tau could explain the heterogeneity seen in PSP disease progression. To test this hypothesis, we performed an extensive biochemical characterisation of the high molecular weight tau species (HMW-Tau) in 20 different brain regions of 25 PSP patients. We found a correlation between the HMW-Tau species and tau seeding capacity in the primary motor cortex, where we confirmed that an elevated 4R-Tau seeding activity correlates with a shorter disease duration. To identify factors that contribute to these differences, we performed proteomic and spatial transcriptomic analysis that revealed key mechanistic pathways, in particular those involving the immune system, that defined patients demonstrating high and low tau seeding capacity. These observations suggest that differences in the tau seeding activity may contribute to the considerable heterogeneity seen in disease progression of patients suffering from PSP.

neuroscience↗