Biology subjects

Alarcon-Riquelme, M. E.

Publications and source records attributed to Alarcon-Riquelme, M. E..

5 recordsLinked to original sources

bioRxiv2025

The SjD Map: An interactive pathway tour into Sjogren's disease signalling mechanisms

ObjectivesSjogrens disease (SjD) remains a major unmet medical challenge, marked by biological complexity, patient heterogeneity, and a lack of curative treatments. To advance the understanding of its pathogenesis and support therapeutic discovery, we developed a comprehensive knowledgebase in the form of a Molecular Interaction Map (MIM). MethodsDifferential expression analysis was performed on peripheral blood samples from SjD patients and healthy controls across three datasets: GSE51092 (190 SjD vs 32 controls), UKPSSR (151 SjD vs 29 controls) and PRECISESADS (304 SjD vs 341 controls). Pathway enrichment analyses provided guidance for MIM construction, which was further refined through literature mining to integrate data-driven results with curated knowledge. ResultsA total of 1,625 differentially expressed genes (DEGs) were identified: 725 from PRECISESADS, 1,162 from GSE51092, and 239 from UKPSSR, with 25 DEGs shared across all three datasets. Among these, nine common DEGs were associated with interferon signalling, reinforcing experimental evidence pointing to its pivotal role in SjD. Enrichment analyses revealed 146 pathways, 43 of which were successfully incorporated into the MIM. The resulting SjD Map freely accessible at https://sjdmap.elixir-luxembourg.org/, comprises 829 molecular entities connected by 598 interactions, with 45% of the information depicted supported by transcriptomic data and 47% derived from literature. The map also includes overlays of experimental data and clinical trial information. ConclusionThis first comprehensive Sjogrens Disease Map, developed through a hybrid data-driven and literature-based approach, offers an integrative view of SjD pathogenesis. It supports visualisation of mechanistic pathways, omics-based data overlays, enables incorporation of user data and drug queries. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=147 SRC="FIGDIR/small/674876v1_ufig1.gif" ALT="Figure 1"> View larger version (60K): org.highwire.dtl.DTLVardef@1bdc517org.highwire.dtl.DTLVardef@1d68077org.highwire.dtl.DTLVardef@18c079forg.highwire.dtl.DTLVardef@487b64_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstractC_FLOATNO C_FIG Key messagesO_LIThis is the first molecular interaction map specific of Sjogrens Disease C_LIO_LIIt enables comprehensive visualisation of affected pathways through integrated transcriptomic and literature-based evidence, following systems biology graphical notation schemes C_LIO_LIThe map may support therapeutic discovery by linking molecular mechanisms to clinical data and drug targets C_LI

systems biology↗

bioRxiv2025

Assessing the Molecular Validity of Spontaneous Lupus Mouse Models and Its Implication for Human Studies

BackgroundSystemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by a loss of self-tolerance, causing inflammation and tissue damage in multiple organs. Animal models have advanced our understanding of SLEs molecular basis, but the FDAs recent elimination of animal testing requirements for drug approval has raised concerns about their validity, prompting a reevaluation of their role in basic research, especially for heterogeneous diseases like SLE. MethodsFour different spontaneous SLE mouse models were studied: MRLlpr/lpr, NZB/W, BXSB.Yaa, and Tlr7.Tg6. Transcriptome sequencing from blood, spleen, and kidney, flow cytometry from the spleen, and cytokines and autoantibody measurement in plasma were performed at four time points. Similar molecular data from human SLE patients was used for the integration. ResultsThe study identified specific molecular pathways driving the phenotype in each mouse model and established optimal time points for future experimental designs. By comparing these pathways to human SLE, the most similar ones and their relationship with disease activity were identified, providing crucial insight into translational relevance. Importantly, disease severity across models was linked to the extent and timing of molecular dysregulations. As expected, MRLlpr/lpr showed the most aggressive phenotype with early immune activation and apoptosis dysregulation, while Tlr7.Tg6 presented late-onset signatures associated with interferon and inflammation. Shared molecular features with human SLE included interferon responses, T and B cell depletion, and neutrophil activation. Integration analysis revealed distinct yet overlapping immune pathways between models and species, with some signatures such as age-associated B cells and double-negative memory T cells being model-specific but potentially relevant to early disease processes. ConclusionsThese findings build a valuable framework for future SLE research, reinforcing the utility of mouse models in studying specific molecular pathways related to human SLE pathogenesis and heterogeneity. The integration of longitudinal mouse data with human transcriptomes highlights the models that best recapitulate key aspects of human disease, offering guidance for the study of specific immunopathological mechanisms or therapeutic targets.

immunology↗

bioRxiv2020

Continental-scale genomic analysis suggests shared post-admixture adaptation in Americas

American populations are one of the most interesting examples of recently admixed groups, where ancestral components from three major continental human groups (Africans, Eurasians and Native Americans) have admixed within the last 15 generations. Recently, several genetic surveys focusing on thousands of individuals shed light on the geography, chronology and relevance of these events. However, despite the fact that gene-flow could drive adaptive evolution, it is not clear whether and how natural selection acted on the resulting genetic variation in the Americas. In this study, we analysed the patterns of local ancestry of genomic fragments in genome-wide data for [~]6,000 admixed individuals from ten American countries. In doing so, we identified regions characterized by a Divergent Ancestry Profile (DAP), in which a significant over or under ancestral representation is evident. Our results highlighted a series of genomic regions with Divergent Ancestry Profiles (DAP) associated with immune system response and relevant medical traits, with the longest DAP region encompassing the Human Leukocyte Antigen locus. Furthermore, we found that DAP regions are enriched in genes linked to cancer-related traits and autoimmune diseases. Then, analyzing the biological impact of these regions, we showed that natural selection could have acted preferentially towards variants located in coding and non-coding transcripts, and characterized by a high deleteriousness score. Taken together, our analyses suggest that shared patterns of post admixture adaptation occurred at continental scale in the Americas, affecting more often functional and impactful genomic variants.

genomics↗

bioRxiv2020

A comprehensive and centralized database for exploring omics data in Autoimmune Diseases

Autoimmune diseases are heterogeneous pathologies with difficult diagnosis and few therapeutic options. In the last decade, several omics studies have provided significant insights into the molecular mechanisms of these diseases. Nevertheless, data from different cohorts and pathologies are stored independently in public repositories and a unified resource is imperative to assist researchers in this field. Here, we present ADEx (https://adex.genyo.es), a database that integrates 82 curated transcriptomics and methylation studies covering 5609 samples for some of the most common autoimmune diseases. The database provides, in an easy-to-use environment, advanced data analysis and statistical methods for exploring omics datasets, including meta-analysis, differential expression or pathway analysis.

bioinformatics↗

bioRxiv2019

The genomic impact of European colonization of the Americas

The human genetic diversity of the Americas has been shaped by several events of gene flow that have continued since the Colonial Era and the Atlantic slave trade. Moreover, multiple waves of migration followed by local admixture occurred in the last two centuries, the impact of which has been largely unexplored.\n\nHere we compiled a genome-wide dataset of [~]12,000 individuals from twelve American countries and [~]6,000 individuals from worldwide populations and applied haplotype-based methods to investigate how historical movements from outside the New World affected i) the genetic structure, ii) the admixture profile, iii) the demographic history and iv) sex-biased gene-flow dynamics, of the Americas.\n\nWe revealed a high degree of complexity underlying the genetic contribution of European and African populations in North and South America, from both geographic and temporal perspectives, identifying previously unreported sources related to Italy, the Middle East and to specific regions of Africa.

genomics↗