Biology subjects

Gomez-Cabanes, B.

Publications and source records attributed to Gomez-Cabanes, B..

4 recordsLinked to original sources

bioRxiv2024

Uncovering sex differences in Parkinson's Disease through metaanalysis of single cell transcriptomic studies

Abundant evidence supports the significant impact of biological sex on various aspects of Parkinson Disease (PD), including incidence, progression, symptoms or response to treatment. The incidence and prevalence of the disease is higher in males, while its age of onset is earlier than in females. There are also sex differences in the symptomatology, both motor and non-motor. In female PD, tremor, pain, depression and dysphagia are predominant, whereas in male PD, freezing of gait, camptocormia, cognitive impairment and urinary dysfunction are more common. Likewise, there are sex differences in the pathophysiology of the disease, related to most of the pathological processes of PD, as is the case of the greater activation of microglia in males or the lower oxidative stress in females. All these findings support the idea that different molecular mechanisms may be involved in PD depending on the sex of the patient. Some explanations for these events are related to biological, genetic, hormonal or environmental factors, such as the possible anti-inflammatory and neuroprotective effect of estrogens. However, the underlying molecular mechanisms have not yet been fully described. Our results show sex differences in gene expression, cell-cell communication and pathway activation in all major brain cell types, highlighting the presence of greater neuroinflammation in men and greater neurodegeneration in the SNpc in men, with the latter appearing to be inverted between sexes when observed in the cortical zone. Finally, we have made all the results available in a publicly accessible webtool, in order to allow the exploration of results to other researchers and to broaden the molecular-level understanding of PD sex differences.

neuroscience↗

bioRxiv2024

Single cell landscape of sex differences in the progression of multiple sclerosis

BackgroundOne of the major challenges in addressing multiple sclerosis is to understand its progression trajectory. The pathological process transitions from acute phases predominantly driven by inflammation to progressive clinical profiles where neurodegeneration takes precedence. It is known that sex plays a crucial role in this heterogeneity; females are two to three times more likely to suffer from multiple sclerosis, while males suffer from more rapid neurodegeneration with greater severity. ResultsTo gain insight into the sex-based molecular differences, we processed single cell datasets from the central nervous system and the peripheral blood, covering the different courses of multiple sclerosis. We generated cell-type specific landscapes, including gene signatures from differentially expressed genes, functional profiling, pathway activation, and cell-cell communication networks for females, males, and their sex differential profiles. Among our findings, we revealed that female neurons may exhibit protective mechanisms against neurodegeneration. In the inflammatory-predominant forms, female immune cells present an inflammatory core driven by the AP-1 transcription factor, while male adaptive immune cells exhibit higher mitochondrial impairment. Conversely, larger differences are reported in CD8+ T cells progressive forms, with males exhibiting cytolytic profiles that may promote neurodegeneration. Complete results can be explored in the interactive webtool https://bioinfo.cipf.es/cbl-atlas-ms/. ConclusionsWe identified cell-type specific sex differences in brain and immune cells that vary in the spectrum of multiple sclerosis. We consider this molecular description a valuable resource to promote future targeted approaches considering the sex of the individual.

neuroscience↗

bioRxiv2024

Unveiling common transcriptomic features between melanoma brain metastases and neurodegenerative diseases

Melanoma represents a critical clinical challenge due to its high incidence rates and unfavorable clinical outcomes. This type of skin cancer presents unique adaptability to the brain microenvironment, but its underlying molecular mechanisms are poorly understood. To further characterize its tumor neurobiology, we explore the relation between the transcriptional profiles of melanoma brain metastasis (MBM) and the neurodegenerative diseases Alzheimers disease, Parkinsons disease, and multiple sclerosis. Through an in silico approach, we unveiled the neurodegenerative signature of MBM when compared to melanoma non-brain metastasis (53 dysregulated genes enriched in 11 functional terms) and to non tumor-bearing brain controls (195 dysregulated genes, mostly involved in development and cell differentiation, chromatin remodeling and nucleosome organization, and translation). Two genes, ITGA10 and DNAJC6, emerged as key potential markers, as they are dysregulated in both scenarios. Lastly, we developed a user-friendly web tool (https://bioinfo.cipf.es/metafun-mbm/) as an open source, so that any user can interactively delve into the results.

cancer biology↗

bioRxiv2022

DNA Methylation Signatures in Breast Cancer: A Systematic Review and Meta-Analysis

Epigenetic changes are involved in the onset and progression of cancer, and the detection of DNA methylation signatures may foster the improvement of diagnosis and prognosis. While the emergence of innovative technologies has fostered numerous studies in breast cancer, many lack statistical power due to the small sample sizes generally involved. In this study, we present a novel meta-analysis that identifies a common pattern of DNA methylation in all breast cancer subtypes. We obtained DNA methylation signatures at the gene and biological function level, identifying those significant groups of genes and functional pathways affected. To achieve this, we conducted a thorough systematic review following PRISMA statement guidelines for the selection of studies on DNA methylation in breast cancer. In total, we gathered four studies (GSE52865, GSE141338, GSE59901 and GSE101443) that were split into 13 comparisons comprising a set of 144 individuals. We discovered that most breast cancer subtypes share a significant deregulation in the immune system and alterations to the cell cycle. This integrative approach combines all available information from public data repositories and possesses greater statistical power than any individual study. Further evaluations of the identified differential biological processes and pathways may support the identification of novel biomarkers and therapeutic targets. Simple summaryThe identification of DNA methylation patterns in breast cancer represents a potentially valuable approach in defining more accurate diagnoses and treatment options. In this study, we applied a novel methodology that integrates the DNA methylation profiles of all studies available in public repositories via systematic review and meta-analysis. The results provide evidence of a common DNA methylation signature in distinct breast cancer subtypes, which reflects a significant deregulation of the immune system and alterations to the cell cycle. Overall, these results may support the selection of disease/treatment biomarkers and the identification of therapeutic targets.

cancer biology↗