Biology subjects

Soler-Saez, I.

Publications and source records attributed to Soler-Saez, I..

8 recordsLinked to original sources

bioRxiv2026

Integrative multi-cohort analysis reveals consistent sex differences in gut microbiota of multiple sclerosis patients

Biological sex is a key determinant in the onset and progression of multiple diseases. In multiple sclerosis (MS), females exhibit higher disease prevalence, earlier onset, and more pronounced inflammatory activity, whereas males tend to experience a more severe neurodegenerative course, characterized by accelerated central nervous system damage and increased brain atrophy. The gut microbiome has emerged as a critical factor in MS, as its composition can either ameliorate or exacerbate disease progression. In this study, we aimed to identify reproducible sex-associated differences in gut microbial composition across independent cohorts of MS patients. Through a systematic search we identified six independent studies based on 16S rRNA gene sequencing, comprising a total of 337 samples. Despite substantial inter-study variability, sex-associated differences were more pronounced in MS patients than in healthy controls. We identified 11 microbial taxa showing significant sex-associated differences in MS, nine enriched in females and two in males. Notably, the female-enriched taxa Eggerthella and Eisenbergiella were associated with specific MS subtypes and higher disability. To facilitate the use of our findings by the scientific community, we developed a freely accessible web-based tool that provides full access to our results. Thus, in this work we identified consistent and reproducible sex differences in the gut microbiota of MS patients, highlighting the importance of incorporating sex as a critical variable in microbiome research, with potential implications for understanding disease heterogeneity in MS. IMPORTANCEMultiple sclerosis (MS) affects females and males differently, but the biological reasons behind these differences are not fully understood. One potential factor is the gut microbiome (i.e., the community of microorganisms living in our intestines) which can influence immune function and disease progression. In this study, we analyzed data from multiple independent cohorts and found consistent differences in gut microbial composition between female and male MS patients. Notably, certain bacteria were more abundant in females and were linked to more severe disease features. We also developed a freely accessible web tool where researchers can explore the complete findings in detail. Our results highlight the importance of considering sex as a key factor in microbiome research and may help guide more personalized approaches to understanding and treating MS.

neuroscience↗

bioRxiv2026

Transposable elements as new players to decipher sex differences in Parkinson Disease

We present a novel integrative analysis of transposable elements (TEs) in 4 single cell RNA-seq (scRNA-seq) datasets of postmortem substantia nigra pars compacta samples of Parkinson Disease (PD) patients matched healthy controls, with the objective of building a cell-type specific trustworthy atlas of TEs that may clarify the role of TEs in sex differences in PD. We have used the soloTE tool to evaluate the TEs expression changes across all snRNA-seq studies identified in our previous systematic review, and then integrated the results using meta-analysis techniques. Finally, we evaluated the possible associations between TEs and protein coding genes by integrating our previous results in this matter with the information of TEs obtained, in order to propose the possible action mechanism by which some of the TEs contribute to PD.

bioinformatics↗

bioRxiv2025

Monocarboxylate transporter 2 is required for the maintenance of myelin and axonal integrity by oligodendrocytes

Neurodegenerative pathologies including multiple sclerosis (MS) are consistently associated with energy deficit in the central nervous system (CNS). This might directly impact myelinating oligodendrocytes as these are particularly vulnerable to metabolic insults. Importantly, oligodendroglial dysfunction and myelin alterations occur in most, if not all neurodegenerative diseases, and are associated with axonal pathology/loss. Thus, elucidating metabolic mechanisms required for oligodendroglial myelin maintenance and axonal support might be crucial to identify therapeutic targets to achieve neuroprotection. While monocarboxylates are important energy fuels for the CNS, their role in myelinating oligodendrocyte function remains unclear. Here we show that, just like neurons, myelinating oligodendrocytes express high affinity monocarboxylate transporter 2 (MCT2) both in mice and humans, which is downregulated in progressive MS. While deletion of MCT2 in mouse oligodendrocytes did not affect the survival of these cells, it resulted in downregulation of lipid synthesis-associated enzymes and failure of myelin maintenance. Moreover, axonal upregulation of lactate dehydrogenase A concomitant with axonal damage was observed but could be alleviated by ketogenic diet. We conclude that oligodendroglial MCT2 is required for myelin maintenance and axonal support, which becomes altered in progressive MS, but may be compensated for by specific metabolic therapies. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=109 SRC="FIGDIR/small/632306v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@2b7b22org.highwire.dtl.DTLVardef@a111fdorg.highwire.dtl.DTLVardef@a410f5org.highwire.dtl.DTLVardef@1556e2f_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

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↗

bioRxiv2023

The role of microRNAs to understand sex-based differences in Alzheimer's disease

BackgroundThe incidence of Alzheimers disease (AD) - the most frequent cause of dementia - is expected to increase as life expectancies rise across the globe. While sex-based differences in AD have previously been described, there remain uncertainties regarding any association between sex and disease-associated molecular mechanisms. Studying sex-specific expression profiles of regulatory factors such as microRNAs (miRNAs) could contribute to more accurate disease diagnosis and treatment. MethodsA systematic review identified five studies of microRNA expression in AD patients that incorporated information regarding the biological sex of samples in the Gene Expression Omnibus repository. A differential microRNA expression analysis was performed, considering disease status and patient sex. Subsequently, results were integrated within a meta-analysis methodology, with a functional enrichment of meta-analysis results establishing an association between altered miRNA expression and relevant Gene Ontology terms. ResultsMeta-analyses of miRNA expression profiles in blood samples revealed the alteration of sixteen miRNAs in female and twenty-two miRNAs in male AD patients. We discovered nine miRNAs commonly overexpressed in both sexes, suggesting a shared miRNA dysregulation profile. Functional enrichment results based on miRNA profiles revealed sex-based differences in biological processes; most affected processes related to ubiquitination, regulation of different kinase activities, and apoptotic processes in males, but RNA splicing and translation in females. Meta-analyses of miRNA expression profiles in brain samples revealed the alteration of six miRNAs in female and four miRNAs in male AD patients. We observed a single underexpressed miRNA in female and male AD patients (hsa-miR-767-5p); however, the functional enrichment analysis for brain samples did not reveal any specifically affected biological process. ConclusionsSex-specific meta-analyses supported the detection of differentially expressed miRNAs in female and male AD patients, highlighting the relevance of sex-based information in biomedical data. Further studies on miRNA regulation in AD patients should meet the criteria for comparability and standardization of information. HighlightsO_LIDeregulation of miRNA expression profiles occurs in a tissue- and sex-specific manner in AD patients C_LIO_LIMeta-analysis of blood samples revealed a partial overlapping pattern of altered miRNA expression in female and male AD patients C_LIO_LIFunctional enrichment based on AD-associated miRNA expression profiles in blood samples reveals sex-based differences: RNA splicing and translation in female AD patients and ubiquitination, regulation of different kinase activities, and apoptotic process in male AD patients C_LIO_LILinks between AD development and miRNA expression in brain tissue also demonstrate the influence of sex C_LI Plain English SummaryAlzheimers disease (AD) - a neurodegenerative disease mainly affecting older patients - is characterized by cognitive deterioration, memory loss, and progressive incapacitation in daily activities. While AD affects almost twice as many females as males, and cognitive deterioration and brain atrophy develop more rapidly in females, the biological causes of these differences remain poorly understood. MicroRNAs (miRNAs) regulate gene expression and impact a wide variety of biological processes; therefore, studying the differential expression of miRNAs in female and male AD patients could contribute to a better understanding of the disease. We reviewed studies of miRNA expression in female and male AD patients and integrated results using a meta-analysis methodology and then identified those genes regulated by the altered miRNAs to establish an association with biological processes. We found sixteen (females) and twenty-two (males) miRNAs altered in the blood of AD patients. Functional enrichment revealed sex-based differences in the affected altered biological processes - protein modification and degradation and cell death in male AD patients and RNA processing in female AD patients. A similar analysis in the brains of AD patients revealed six (females) and four (males) miRNAs with altered expression; however, our analysis failed to highlight any specifically altered biological processes. Overall, we highlight the sex-based differential expression of miRNAs (and biological processes affected) in the blood and brain of AD patients.

neuroscience↗

bioRxiv2022

ISCB RSG-Spain and highlights from the VIII Spanish Student Symposium in Bioinformatics and Computational Biology in 2021

The Regional Student Group of Spain is recognized by the Student Council and the International Society for Computational Biology. The objective of these institutions is to connect and share useful information among all professionals and students working in the field of bioinformatics and computational biology. In this article, we intend to present and publicize RSG-Spain, the Spanish ISCB regional student group, by relating its recent history of a growing community of students and young professionals and how it helps their development in the field. RSG-Spain, since its creation, has been involved in the organization of events with the aim of gathering bioinformaticians in the country and promoting research and collaboration in the field. Here the VIII Student Symposium held online in 2021 is presented, analyzing the output of the event and showing the main challenges found in its organization.

scientific communication and education↗