Alberto Gómez-Carballa

Can epigenomic signatures of exceptional longevity transcend species boundaries? By comparing findings from a previously published epigenomic study of Jonathan, a 194-year-old giant tortoise, based on buccal scrape and saliva samples, with the analyses of publicly available DNA methylation data from exceptionally long-lived humans based on peripheral blood mononuclear cells (PBMCs), this comparative study reveals intriguing molecular parallels across evolutionarily distant species. Human individuals aged 110+ years exhibited significantly higher global methylation entropy than those aged 60-82 years. Furthermore, 12 candidate genes displayed a distinctive promoter methylation entropy profile, with lower values at the youngest and oldest ages than in intermediate-age groups. Strikingly, these genes were enriched in telomere-related biological processes, highlighting a compelling link between epigenomic patterns and pathways implicated in aging. The correspondence between the findings in humans and previously reported observations in Jonathan suggests testable hypotheses about epigenomic signatures of exceptional longevity that may be conserved across species and extend beyond tissue-specific effects.

Music-based interventions (MIs) have shown promise in autism spectrum disorder (ASD), yet the molecular mechanisms underlying their effects remain poorly understood. The transcriptomic response to music exposure in individuals with ASD and healthy controls (HCs) was analyzed using buccal swab samples and a targeted NanoString gene expression panel. The discovery cohort included baseline and post-intervention samples, whereas the validation cohort added a 25-minute intermediate sample to assess transcriptional dynamics. Thirty-three candidate genes were identified in the discovery cohort, of which 20 (61%) remained significantly differentially expressed in the independent validation cohort, including 13 that withstood multiple-testing correction. Replicated genes included several key regulators of innate immunity and inflammatory signaling, such as CXCL8, MYD88, RELA, PTGS2, PTPRC, SELL, LYN, and LTBR. Functional enrichment analyses revealed robust innate immune and inflammatory pathways, characterized by TLR/IL-1-MYD88 signaling, cytokine activity, leukocyte activation, and antimicrobial responses. Co-expression network analysis identified coordinated remodeling of immune transcriptional programs in ASD. Consensus feature selection identified a two-gene signature that accurately discriminated pre- and post-musical stimulation samples in ASD but not in HCs. The same signature detected transcriptomic responses after only 25 minutes of music exposure by discriminating baseline and intermediate samples, with intermediate expression levels between baseline and post-intervention values, suggesting a progressive duration-dependent response. These findings demonstrate a reproducible transcriptional response to music in ASD across independent cohorts implicating neuroimmune pathways. The resulting transcriptional signature supports the development of minimally invasive biomarkers for monitoring MIs in neurodevelopmental disorders.

Music elicits complex emotional, cognitive, and physiological responses, yet the molecular mechanisms underlying these effects remain poorly understood. Tear fluid is an accessible biofluid that reflects both systemic and local physiology, providing a unique opportunity to investigate the biological effects of musical stimulation. Quantitative mass spectrometry-based proteomics was performed on paired tear samples (n = 336) collected before and after exposure to a standardized musical stimulus in two independent cohorts of healthy participants, including both music-stimulated and music-unstimulated individuals. Integrative analyses, including differential expression, functional enrichment, co-expression network, correlation, and machine-learning approaches, identified reproducible molecular responses across cohorts. Fourteen proteins, including PRTN3, LEG3, CATD, IGHG2, and ZA2G, remained significant after multiple-testing correction and showed concordant regulation in the stimulated cohorts but not in controls. Functional enrichment converged on innate immune, inflammatory, host-defense, and extracellular signaling pathways, and consensus network analysis identified reproducible immune-related modules. The 14-protein signature robustly discriminated pre- and post-stimulation samples, with no effect detected in the unstimulated control groups. These findings support tear proteomics as a promising non-invasive approach for investigating the molecular basis of auditory and emotional experiences.

Galicia, at the westernmost edge of Europe, exhibits distinctive genetic traits compared to other Iberian populations. We present the first whole‐genome sequencing (WGS) study of a Galician population (GALOMICS; n = 91; 17.2 M variants; https://galomics.genpob.eu ), analyzed alongside WGS data from other Spanish and continental populations ( n = 1078). Contrary to recent claims of extreme genetic stratification, Galicia's structure reflects broader Iberian patterns, characterized by one major genetic cluster and four minor, localized ones. Analyses of the Spanish National DNA Bank (NDNAB; n = 453) confirm this pattern, with three Galician clusters, one clearly predominant. Phylogenetic analysis places Galician clusters on terminal, recently diverged branches, challenging earlier models suggesting ancient separation. Slightly elevated homozygosity, driven by the Porto do Son cluster, suggests mild regional inbreeding. A notable North African/Middle Eastern ancestry component (13.5%–16.5%) appears, likely introduced via trans‐Mediterranean contact ca. 620–670 ce , predating the Islamic conquest of 711 ce , with a subtle south‐to‐north gradient and a male‐biased signal (Y‐DNA: 21.2%; mtDNA: 1.1%). This calls for reexamining assumptions about Islamic‐era ancestry. Finally, Polygenic Risk Scores for common diseases (e.g., cancer, Alzheimer's disease, diabetes, autism) show geographic variability aligned with genetic substructure, highlighting the relevance of regional genomics to public health policy.

Saliva-based RNA sequencing (RNA-seq) poses technical challenges due to high bacterial content, RNA degradation, and sample heterogeneity. This study investigates the transcriptional effects of music exposure in individuals with autism spectrum disorder (ASD) using this non-invasive approach. To address saliva-specific limitations, we employed two complementary library preparation methods, Poly-A selection and Human-Enriched protocols, allowing us to maximize human transcript detection and ensure reproducibility. By merging them, we ensured reproducibility and captured both host and microbial signals. While each dataset individually revealed a limited number of differentially expressed genes (DEGs), their integration enhanced biological resolution. Among the consistently modulated genes were HERC6 , TSPAN5 , and REM2 , pointing to music-induced transcriptional changes relevant to neurodevelopmental and immune processes. Functional enrichment analyses highlighted pathways involved in immune regulation, oxidative phosphorylation, and epithelial differentiation. These findings align with evidence of immune dysregulation, mitochondrial dysfunction, and altered cellular communication in ASD. Importantly, co-expression network analysis identified modules significantly correlated with music exposure. Notably, the AKNA module, previously associated with ASD risk, was downregulated and enriched for Ras-related GTPase signaling and immune pathways, suggesting that music may modulate intracellular signaling and inflammation. Conversely, upregulation of the UBE2D3 module pointed to activation of endoplasmic reticulum stress response mechanisms, a known contributor to ASD neurodevelopmental deficits. These results suggest that music engages specific stress-adaptive and immunomodulatory networks in buccal cells, potentially reflecting systemic effects. Our exploratory metagenomic analysis highlights 15 microbial species with consistent abundance shifts across both methods. Notably, Acidipropionibacterium acidipropionici and Propionibacterium freudenreichii , associated with propionic acid production, emerged as music-responsive taxa. Elevated propionic acid has been implicated in ASD-like behaviors and neuroinflammation, suggesting a microbiota-mediated pathway. Music may influence both host gene expression and oral microbiota, potentially affecting neuroimmune processes via the microbiota–brain axis. Although exploratory, the results support the feasibility of using saliva for integrated molecular profiling in ASD.

Music-based interventions have shown promise in aiding recovery in individuals with brain damage (BD), including acquired and traumatic brain injury (ABI and TBI). To investigate the underlying molecular mechanisms, we conducted a proof-of-concept study integrating transcriptomic and epigenomic data. We compared gene expression changes driven by musical stimuli in healthy individuals exposed to music with transcriptomic data from TBI patients, identifying 154 common differentially expressed genes (DEGs) affected in TBI and impacted by music, including STK35, HNRNPA0, MT-CYB, and MT-ND2. These genes are notably involved in mitochondrial function, synaptic plasticity, and neurodegenerative processes. Epigenomic analysis revealed that 92 of these DEGs also exhibited significant differential methylation in TBI samples, particularly in genes associated with neurodevelopment, neuroinflammation, and mood regulation. Pathway enrichment and cross-validation in independent datasets of TBI patients highlighted the cGMP-PKG signaling pathway, a key regulator of memory and plasticity. Co-expression network analysis further revealed six gene modules significantly associated with TBI, including modules centered on TXNIP and ALG13, genes previously implicated in neuroinflammation and epilepsy, two conditions commonly associated with TBI. Interestingly, several hub genes from these modules also showed sensitivity to musical stimuli, suggesting that music may target biologically relevant networks involved in TBI pathology. These findings provide preliminary evidence that music exposure may modulate gene expression and methylation in ways that support neural repair and functional recovery. This molecular insight reinforces the potential of music as a biologically grounded component of neurorehabilitation. Future studies should directly assess transcriptomic and epigenomic responses to music-based interventions in BD patients.

Galicia, located at the westernmost edge of Europe, has been reported to exhibit distinctive genetic traits compared to other Iberian populations. We present the first whole-genome sequencing (WGS) study of a Galician population (GALOMICS [GAL]; n = 91, 17.2 million variants; https://galomica.genpob.eu/ ), assessing its genetic variability in comparison with WGS data from other Spanish regions and continental populations ( n = 1,078). Contrary to recent claims of extreme genetic stratification, the population structure of Galicia aligns with broader Iberian patterns, with one dominant cluster homogeneously distributed and four minor, more localized clusters. Genome-wide analyses of the Spanish National DNA Bank dataset (NDNAB; n = 453) support these findings, identifying only three Galician clusters, again with one overwhelmingly predominant. Phylogenetic analyses challenge earlier interpretations that placed Galicians at the deepest Iberian genetic node; instead, Galician clusters form terminal branches, suggesting recent diversification. Analysis of runs of homozygosity indicates slightly higher inbreeding compared to other European populations, primarily driven by the ‘Porto do Son’ cluster, which raises the regional average. We identified a significant North African/Middle Eastern autosomal ancestry component (13.5%–16.5%), despite its distance from historically Arab-influenced regions. Genomic analyses point to an admixture event ca. 620–670 CE that introduced North African/Middle Eastern ancestry into a largely European gene pool. The signal, likely stemming from trans-Mediterranean contacts predating the 711 CE Islamic incursion and well before the Reconquista , shows a subtle South-to-North decline, suggesting a southern entry route. Y-chromosome (21.2%) and mitochondrial DNA (1.1%) analyses indicate a male-biased influx, pointing to a predominantly paternal contribution. This observation calls for a reevaluation of the commonly held assumption that Islamic rule alone accounts for North African ancestry in Iberia. Analysis of polygenic risk scores for common diseases (including breast and ovarian cancer, Alzheimer’s, schizophrenia, and type 2 diabetes) reveals distinct micro-geographical patterns of disease risk in the region, stratified by genetic clusters. These insights highlight the importance of further research into implications for public health policy.

The tuberculosis (TB) lesion is a complex structure, contributing to the overall spectrum of TB. We characterise, using RNA sequencing, 44 fresh human pulmonary TB lesion samples from 13 TB individuals (drug-sensitive and multidrug-resistant TB) undergoing therapeutic surgery. We confirm clear separation between the TB lesion and adjacent non-lesional tissue, with the lesion samples consistently displaying increased inflammatory profile despite heterogeneity. Using weighted correlation network analysis, we identify 17 transcriptional modules associated with TB lesion and demonstrate a gradient of immune-related transcript abundance according to spatial organization of the lesion. Furthermore, we associate the modular transcriptional signature of the TB lesion with clinical surrogates of treatment efficacy and TB severity. We show that patients with worse disease present an overabundance of immune/inflammation-related modules and downregulated tissue repair and metabolism modules. Our findings provide evidence of a relationship between clinical parameters, treatment response and immune signatures at the infection site.

Mycoplasma pneumoniae causes atypical pneumonia in children and young adults. Its lack of a cell wall makes it resistant to beta-lactams, which are the first-line treatment for typical pneumonia. Current diagnostic tests are time-consuming and have low specificity, leading clinicians to administer empirical antibiotics. Using a LASSO regression simulation approach and blood microarray data from 107 children with pneumonia (including 30 M. pneumoniae) we identify eight different transcriptomic signatures, ranging from 3-10 transcripts, that differentiate mycoplasma pneumonia from other bacterial/viral pneumonias with high accuracy (AUC: 0.84–0.95). Additionally, we demonstrate that existing signatures for broadly distinguishing viral/bacterial infections and viral/bacterial pneumonias are ineffective in distinguishing M. pneumoniae from viral pneumonia. The new signatures are successfully validated in an independent RNAseq cohort of children with pneumonia, demonstrating their robustness. The high sensibility of these signatures presents a valuable opportunity to guide the treatment and management of M. pneumoniae pneumonia patients.