Biology subjects

Grillo-Risco, R.

Publications and source records attributed to Grillo-Risco, R..

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↗

bioRxiv2026

MetaOmixTools: an interactive web suite for meta-analysis of ranked features and functional enrichment

The growing number of omics datasets in public repositories provides an opportunity to enhance data reusability through data integration; however, complex statistical barriers often hinder the effective combination of independent studies. To address this problem, we present MetaOmixTools, an interactive web-based suite that streamlines the meta-analysis of ranked feature lists and functional enrichment profiles. The platform integrates two primary modules - MetaRank and MetaEnrich within a code-free environment. MetaRank generates robust consensus rankings from multiple lists by implementing weighted (e.g., Rank Product) and unweighted (e.g., Robust Rank Aggregation) strategies, while MetaEnrich performs functional meta-analyses by combining probability values from individual over-representation analyses using established statistical techniques. Using case studies, we established consensus rankings for acute spinal cord injury across heterogeneous platforms, identifying conserved inflammatory marker genes in the upregulated gene list (e.g., Slpi, Ccl2, Msr1) and synaptic loss genes in the downregulated gene list (e.g., Kcna2, Dao, Ppp1r1b), and also characterized inverse functional intersections between melanoma brain metastasis and neurodegenerative diseases. By providing intuitive, real-time visualization and reproducible workflows, MetaOmixTools empowers the research community to extract consistent biological insights from multi-study data. We have made MetaOmixTools freely available at https://bioinfo.cipf.es/metaomixtools/. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=163 HEIGHT=200 SRC="FIGDIR/small/707748v2_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@c1974org.highwire.dtl.DTLVardef@5b4b38org.highwire.dtl.DTLVardef@1a753f8org.highwire.dtl.DTLVardef@79fb20_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

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

A spinal cord injury time and severity consensus transcriptomic reference suite in rat reveals translationally-relevant biomarker genes

Spinal cord injury (SCI) is a devastating condition that leads to motor, sensory, and autonomic dysfunction. Current therapeutic options remain limited, emphasizing the need for a comprehensive understanding of the underlying SCI-associated molecular mechanisms. This study characterized distinct SCI phases and severities at the gene and functional levels, focusing on biomarker gene identification. Our approach involved a systematic review, individual transcriptomic analysis, gene meta-analysis, and functional characterization. We compiled a total of fourteen studies with 273 samples, leading to the identification of severity-specific biomarker genes for injury prognosis (e.g., Srpx2, Hoxb8, Acap1, Snai1, and Aadat) and phase-specific genes for the precise classification of the injury profile (e.g., Il6, Fosl1, Cfp, C1qc, Cp). We investigated the potential transferability of severity-associated biomarkers and identified a twelve-gene signature that predicted injury prognosis from human blood samples. We also report the development of MetaSCI-app - an interactive web application designed for researchers - that allows the exploration and visualization of all generated results (https://metasci-cbl.shinyapps.io/metaSCI). Overall, we present a transcriptomic reference and provide a comprehensive framework for assessing SCI considering severity and time perspectives. TeaserA transcriptomic meta-analysis of spinal cord injury provides a consensus reference and biomarker genes for injury phase/severity.

neuroscience↗

bioRxiv2021

Sex bias evaluation of classic and novel Housekeeping Genes in adipose tissue through the massive analysis of transcriptomics data

BackgroundAs the housekeeping genes (HKG) generally involved in maintaining essential cell functions are typically assumed to exhibit constant expression levels across cell types, they are commonly employed as internal controls in gene expression studies. Nevertheless, HKG may vary gene expression profile according to different variables introducing systematic errors into experimental results. Sex bias can indeed affect expression display, however, up to date, sex has not been typically considered as a biological variable. MethodsIn this study, we evaluate the expression profiles of six classical housekeeping genes (four metabolic: GAPDH, HPRT, PPIA, and UBC, and two ribosomal: 18S and RPL19) to determine expression stability in adipose tissues (AT) of Homo sapiens and Mus musculus and check sex bias and their overall suitability as internal controls. We also assess the expression stability of all genes included in distinct whole-transcriptome microarrays available from the Gene Expression Omnibus database to identify sex-unbiased housekeeping genes (suHKG) suitable for use as internal controls. We perform a novel computational strategy based on meta-analysis techniques to identify any sexual dimorphisms in mRNA expression stability in AT and to properly validate potential candidates. ResultsJust above half of the considered studies informed properly about the sex of the human samples, however, not enough female mouse samples were found to be included in this analysis. We found differences in the HKG expression stability in humans between female and male samples, with females presenting greater instability. We propose a suHKG signature including experimentally validated classical HKG like PPIA and RPL19 and novel potential markers for human AT and discarding others like the extensively used 18S gene due to a sex-based variability display in adipose tissue. Orthologs have also been assayed and proposed for mouse WAT suHKG signature. All results generated during this study are readily available by accessing an open web resource (https://bioinfo.cipf.es/metafun-HKG) for consultation and reuse in further studies. ConclusionsThis sex-based research proves that certain classical housekeeping genes fail to function adequately as controls when analyzing human adipose tissue considering sex as a variable. We confirm RPL19 and PPIA suitability as sex-unbiased human and mouse housekeeping genes derived from sex-specific expression profiles, and propose new ones such as RPS8 and UBB. HighlightsO_LIA computational strategy based on massive data analysis revealed that an accurate experimental design for adipose tissue requires the adequate selection of a sex-unbiased housekeeping genes (HKG). C_LIO_LIThe extensively used 18S gene displays sex-based variability in adipose tissue, although PPIA and RPL19 do not, and hence, represent robust HKG. C_LIO_LINew sex-unbiased human and mouse candidate HKG: RPS8 and UBB. C_LIO_LImetafun-HKG (https://bioinfo.cipf.es/metafun-HKG): a freely available web tool to allow users to review stable expression levels of candidate HKG along the large volume of FAIR data. C_LI

genomics↗

bioRxiv2021

MetaFun: Unveiling sex differences in multiple omics studies through comprehensive functional meta-analysis

While sex-based differences in various health scenarios have been thoroughly acknowledged in the literature, we lack a deep analysis of sex as a variable in this context. To fill this knowledge gap, we created MetaFun as an easy-to-use web-based tool to meta-analyze multiple transcriptomic datasets with a sex-based perspective to gain major statistical power and biological soundness. Furthermore, MetaFun can be used to perform case-control meta-analyses, allowing researchers with basic programming skills to access this methodology. Availability and implementationMetaFun is freely available at http://bioinfo.cipf.es/metafun The back end was implemented in R and Java, and the front end was developed using Angular Contactfgarcia@cipf.es, mhidalgo@cipf.es Supplementary informationR code available at https://gitlab.com/ubb-cipf/metafunr

bioinformatics↗