Ticks are ectoparasites that modulate host responses to sustain prolonged blood feeding, and in Ixodes ricinus, salivary microRNAs (miRNAs) represent promising candidates for manipulating host gene expression. Using phylogenetic footprinting combined with cooperative targeting analysis, we predicted deeply conserved miRNA–mRNA interactions that appear to contribute to tick lifecycle completion and tick’s ability to parasitize diverse…

Background Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by loss of self-tolerance, causing inflammation and tissue damage in multiple organs. Although animal models have advanced our understanding of SLE’s molecular basis, recent regulatory changes and longstanding concerns regarding reproducibility and translatability have renewed the need to critically evaluate how these models mirror…

Objective: To develop a blood-based algorithm using cell-free DNA (cfDNA) methylation profiles to diagnose and stratify patients with COPD according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification.Methods: Between 2021 and 2023, 166 participants were enrolled, including patients with COPD (N = 80) and healthy controls (N = 86) from three hospitals in Andalusia….

ObjectivesSystemic lupus erythematosus (SLE) is a complex autoimmune disease with pronounced clinical heterogeneity and symptom burden. Despite growing knowledge of SLE biology, sensitive noninvasive biomarkers for monitoring disease activity remain lacking. This study aimed to characterise the breath metabolome in SLE and to explore associations between volatile organic compounds (VOCs) and clinical features, including disease…

Objectives Early trials of CD19-chimeric antigen receptor (CAR) T cell therapy in systemic lupus erythematosus (SLE) show promise, but the molecular mechanisms underlying its disease-modifying effects remain unclear. We aimed to compare biological profiles and alterations following CD19-CAR T cell versus standard pharmacotherapy in SLE. Methods Pseudo-bulk gene expression derived from single-cell RNA sequencing of…

Reproductive dysfunction of captive-bred males of the Senegalese sole ( Solea senegalensis ) represents a significant bottleneck for its aquaculture, as these fish exhibit reduced sperm production and impaired fertility compared to wild-bred counterparts acclimated to farm conditions. To elucidate the cellular and molecular mechanisms underlying this phenomenon, single-nuclei RNA sequencing was performed on gonadal…

ObjectivesSjögren’s disease (SjD) is clinically and biologically heterogeneous, and no immunomodulatory drug has yet demonstrated efficacy in phase 3 trials. We previously identified 4 transcriptomic endotypes in SjD patients using whole-blood RNA sequencing. We hypothesised that these endotypes may predict differential therapeutic responses.MethodsWe analysed clinical, biological, and transcriptomic data from 3 randomised controlled trials evaluating…

Objective Tumornecrosis factor inhibitors (TNFi) have significantly improved rheumatoid arthritis (RA) management, yet variability in patient response remains a substantial challenge, with approximately 40% of patients discontinuing TNFi due to nonresponse or adverse effects. This study aimed to identify biomarkers predictive of adalimumab treatment response using whole‐blood transcriptomics, leveraging machine learning models for data mining…

ObjectivesTo gain insights into the pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE) and identify potential drug targets through investigation of whole-blood human transcriptome.MethodsWe analysed differentially expressed genes in peripheral blood from active central nervous system (CNS) lupus (n = 26) and active non-neuropsychiatric SLE (n = 38) patients versus healthy controls (n = 497) from the European PRECISESADS project (NTC02890121). We…

Although genome-wide association studies have provided valuable insights into the genetic basis of complex traits and diseases, translating these findings to causal genes and their downstream mechanisms remains challenging. We performed trans expression quantitative trait locus (trans-eQTL) meta-analysis in 3734 lymphoblastoid cell line samples, identifying four robust loci that replicated in an independent multi-ethnic dataset…

The “omnigenic” hypothesis postulates that the polygenic effects of common variants on a typical complex trait coalesce on relatively few core genes through trans-effects on their expression. Our aim was to identify core genes for systemic lupus erythematosus (SLE) by testing for association with genome-wide aggregated trans-effects (GATE) scores for gene expression in a large…

Introduction Mathematical models are powerful tools that can be used to advance our understanding of complex diseases. Autoimmune disorders such as systemic lupus erythematosus (SLE) are highly heterogeneous and require high-resolution mechanistic approaches. In this work, we present ONIDsc, a single-cell regulatory network inference model designed to elucidate immune-related disease mechanisms in SLE. Methods ONIDsc…

ObjectivesThis study aimed to identify and validate novel autoantibodies that reflect global and organ-specific disease activity in systemic lupus erythematosus (SLE).MethodsPlasma samples were screened for IgG and IgA seroreactivity against 1609 protein autoantigens using a microarray (i-Ome Discovery; Sengenics). We determined differentially abundant autoantibodies (daAAbs) in patients with SLE vs healthy controls within a discovery…

ObjectivesIn response to the urgent unmet needs of heterogeneity, unpredictability, and diagnostic delay in systemic lupus erythematosus (SLE), we aimed to identify and validate new immunoglobulin (Ig)G and IgA autoantibody specificities.MethodsUsing a KoRectly EXpressed technology–based microarrays (i-Ome Discovery; Sengenics), we screened for circulating IgG and IgA autoantibodies against 1609 proteins in 2 independent cohorts (discovery:…

The 22q11.2 deletion syndrome (22qDS) is a human disorder where the majority of clinical manifestations originate during embryonic development. 22qDS is caused by a microdeletion in one chromosome 22, including DGCR8, an essential gene for microRNA (miRNA) production. However, the impact of DGCR8 hemizygosity on human development is still unclear. In this study, we generated…

Objective Nongenetic factors influence systemic sclerosis (SSc) pathogenesis, underscoring epigenetics as a relevant contributor to the disease. We aimed to unravel DNA methylation abnormalities associated with SSc through an epigenome‐wide association study. Methods We analyzed DNA methylation data from whole‐blood samples in 179 patients with SSc and 241 unaffected individuals to identify differentially methylated positions…

BackgroundInterpreting biological system changes requires interpreting vast amounts of multi-omics data. While user-friendly tools exist for single-omics analysis, integrating multiple omics still requires bioinformatics expertise, limiting accessibility for the broader scientific community.ResultsBiomiX tackles the bottleneck in high-throughput omics data analysis, enabling efficient and integrated analysis of multiomics data obtained from two cohorts. BiomiX incorporates diverse…

The identification of shared molecular mechanisms across systemic inflammatory autoimmune diseases with overlapping clinical manifestations has prompted research into the underlying genetics that could be driving these manifestations; elucidating these genes could aid in the diagnosis, treatment and outcome prediction of these complex diseases.

BackgroundPhenotypic data comparison is essential for disease association studies, patient stratification, and genotype–phenotype correlation analysis. To support these efforts, the Global Alliance for Genomics and Health (GA4GH) established Phenopackets v2 and Beacon v2 standards for storing, sharing, and discovering genomic and phenotypic data. These standards provide a consistent framework for organizing biological data, simplifying their…

The heterogeneity of systemic lupus erythematosus (SLE) can be explained by epigenetic alterations that disrupt transcriptional programs mediating environmental and genetic risk. This study evaluated the epigenetic contribution to SLE heterogeneity considering molecular and serological subtypes, genetics and transcriptional status, followed by drug target discovery. We performed a stratified epigenome-wide association studies of whole blood…