Biology subjects

Salas, A.

Publications and source records attributed to Salas, A..

At least 19 recordsLinked to original sources

bioRxiv2026

A reproducible buccal transcriptomic response to music exposure in autism spectrum disorder: insights into the oral-brain axis

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.

genomics↗

bioRxiv2026

Host gene-expression signatures accurately distinguish bacterial, viral, and inflammatory diseases in febrile children across multiple cohorts

Accurate discrimination between viral, bacterial, and inflammatory diseases in febrile children remains a major clinical challenge that contributes to diagnostic uncertainty, inappropriate antimicrobial use, and suboptimal clinical management. Host blood transcriptomics offer a promising strategy to improve diagnostic precision. The present study represents the largest integrative multi-cohort pediatric study of transcriptomic biomarker discovery, validation, and confirmation reported to date, integrating harmonized public transcriptomic datasets with an independent confirmation cohort comprising well-phenotyped patients to identify parsimonious host-response signatures for differentiating viral, bacterial, and inflammatory diseases. Transcriptomic signatures were derived from an integrated retrospective microarray multi-cohort (n=1,683), independently validated in a retrospective RNA-seq cohort (n=767), and confirmed by digital PCR in an independent cohort (n=29), demonstrating reproducibility across patient populations, transcriptomic technologies, and analytical platforms. The analysis identified binary signatures and a unified multiclass classifier that consistently achieved high diagnostic accuracy across all three study phases and outperformed more than 30 published host transcriptomic signatures. Decision curve analysis showed substantially greater clinical net benefit than C-reactive protein across clinically relevant decision thresholds. These findings provide a strong foundation for clinically deployable molecular diagnostics to improve patient triage, antimicrobial stewardship, and precision medicine in childhood infections.

genomics↗

bioRxiv2026

A prospective multi-cohort study identifies reproducible molecular responses to musical stimulation in the human tear proteome

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.

molecular biology↗

bioRxiv2026

From prehistory to present-day: How isolation shaped the distinct genomic makeup of Italian Alpine valleys

Historically, the eastern Italian Alps have provided crucial geographic corridors for cultural and genetic exchange between the Mediterranean region and Central and Northern Europe. Although recent archaeogenomic data suggest a strong regional persistence of Anatolian Neolithic ancestry followed by the arrival of Yamnaya-related components during the Bronze Age, the genomic landscape of modern Alpine populations remains largely unmapped. In this study, we verified the persistence of these signals in the present-day Rendena and Ledro Valleys by integrating novel complete mitochondrial genomes (N=185) and genome-wide SNP data (N=96), the latter combined with a novel Italian genomic dataset (N=139). Our findings show that the Rendena and Ledro populations form a distinct "modern Alpine" genomic group, which retains a significant proportion of early European Neolithic ancestry, aligning with ancient eastern Italian Alpine individuals and modern Sardinians. More recently, geographic isolation and localized genetic drift appear to have shaped the two valleys differently. Demographic reconstructions reveal asynchronous population declines over the past two millennia, followed by a sharp, synchronized bottleneck 200-300 years ago, which coincided with historical plague outbreaks. Remarkably, this structured drift persisted at an extremely fine microgeographic scale within the valleys, resulting in internal genetic subclusters that directly correlate with local topography. This micro-differentiation was likely maintained by steep geographic barriers and/or local endogamous practices. This study ultimately underscores how geographic barriers and isolation can preserve ancient genomic components and shape highly localized genetic structures over centuries even to the modern day.

evolutionary biology↗

bioRxiv2026

Allele-specific correction of dominant Best vitelliform macular dystrophy in patient-derived retinal pigment epithelium

Autosomal dominant Best vitelliform macular dystrophy (BVMD) caused by variants in the BEST1 gene is characterized by dysfunction of the macular retinal pigment epithelium (RPE) and secondary degeneration of the photoreceptors. There are currently no approved treatments for BVMD, and owing to its dominant nature, there remains uncertainty regarding the utility of traditional gene augmentation. Here we evaluated whether a dominant pathogenic BEST1 allele can be corrected by base editing in differentiated RPE cells. We identified a patient with a likely pathogenic BEST1 c.851A>G (p. Tyr284Cys) variant that was amenable to cytidine base editing. After establishing patient-derived induced pluripotent stem cells (iPSCs), we corrected the pathogenic variant in the iPSCs to obtain corrected iPSCs with the same genetic background. Corrected iPSC-derived RPE exhibited normalized monolayer appearance, improved barrier integrity, reduced cell death, and restored RPE-specific transcriptome. We then used a dual adeno-associated virus (AAV) split-intein system to deliver a CRISPR-associated protein 9 cytidine base editor (SpCas9-CBE) to BEST1 c.851A>G mutant RPE monolayers and achieved editing of the pathogenic allele with a maximum efficiency of 13.42 {+/-} 3.64% (mean {+/-} SD). Together, these results demonstrate progress towards allele-specific base editing in a dominantly inherited retinal disorder.

neuroscience↗

bioRxiv2026

A JAK-STAT-activated myeloid hub at ulceration sites underlies resistance to anti-TNF therapy in Crohn's disease

Despite major advances in immunotherapies, durable disease control in immune-mediated inflammatory diseases (IMIDs) is frequently limited by resistance driven by maladaptive immune programs, resulting in progressive tissue damage. Myeloid cells are central effectors across IMIDs, including inflammatory bowel disease (IBD), yet how discrete myeloid states govern disease progression and therapeutic response remains incompletely defined. Here, using integrative single-cell transcriptomic and molecular analyses of inflamed human ileum in Crohns disease (CD), we identify combinatorial transcriptional programs that revealed previously unrecognized axes of monocyte-macrophage (mo-mac) heterogeneity. These myeloid states and programs were conserved and validated across multiple independent cohorts. We delineate a pathogenic mo-mac subset, interferon-associated inflammatory monocytes (IFIM), shaped by convergent NF-{kappa}B and IFN{gamma} signaling and enriched in advanced disease. Baseline abundance of IFIM programs predicted resistance to anti-TNF therapy and severe postoperative recurrence, with IFIM-derived ligands sustaining epithelial injury. IFIM exhibited robust JAK-STAT activation, indicating susceptibility to JAK inhibition with clinically approved agents, including upadacitinib. Exemplified by IFIM-driven inflammation, these findings identify pathogenic myeloid state remodeling as a molecular basis of anti-TNF resistance and provide a framework for mechanism-guided therapeutic strategies across chronic inflammatory diseases.

immunology↗

bioRxiv2025

Long-Term Organ Culture Reveals Differential Stem Cell-Driven Remodelling in Myometrium and MED12-Mutant Uterine Leiomyoma

Uterine leiomyomas or fibroids are highly prevalent benign tumors of the female reproductive tract, often causing significant symptoms and requiring surgical intervention, leading to substantial healthcare costs worldwide. Their molecular pathogenesis remains incompletely understood, but evidence suggests that somatic stem cells play a pivotal role in myometrial growth, whereas a genetic alteration, particularly mutations in MED12, may transform a myometrial stem cell into a tumor-initiating cell, promoting fibroid growth. In organ cultures of fibroids and myometrium, most differentiated cells degenerated by day 7, whereas stem cells remained quiescent and viable within their native niches. Notably, between days 15 and 29, hypoxia-induced activation triggered stem cell proliferation and differentiation within the ex vivo slices. Transcriptomic profiling revealed statistically significant upregulation of stemness-associated genes, including HMGA, ITG, KLF, HOX, and SOX family members, in long-term cultured slices compared with baseline tissue, and between normal and tumor cultures. Reactome pathway enrichment analysis further identified distinct metabolic, extracellular matrix remodeling, immune surveillance, angiogenic, and cell death- related programs distinguishing myometrial from leiomyoma cultures. Furthermore, previously reported gene and pathway differences between healthy and fibroid tissues were robustly confirmed, validating the culture model. In conclusion, our findings establish long-term organ culture as a powerful, physiologically relevant platform for investigating stem cell dynamics in myometrium and uterine leiomyoma. They also provide proof of concept for extending this approach to other tissue types, enabling the discovery of mechanisms underlying stem cell activation, differentiation, and death, with broad translational potential in regenerative medicine and cancer biology.

molecular biology↗

bioRxiv2025

Decoding the peripheral transcriptomic and meta-genomic response to music in Autism Spectrum Disorder via saliva-based RNA sequencing

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.

genomics↗

bioRxiv2025

Can music modulate gene expression involved in traumatic brain injury? An integrative transcriptomic and epigenomic proof of concept

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.

genomics↗

bioRxiv2025

Whole-genome sequencing in Galicia reveals male-biased pre-Islamic North African ancestry, subtle population structure, and micro-geographic patterns of disease risk

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, Alzheimers, 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.

genomics↗

bioRxiv2025

TL1A-activated T cells remodel the rectal mucosa in Crohn's disease patients with perianal fistulizing disease

BackgroundPerianal fistulizing disease (PFD) is a complication that affects about 20% of Crohns disease (CD) patients whose etiology remains unknown. ObjectivesTo identify predisposing events driving fistula formation. DesignRectal biopsies from CD patients with or without PFD (CD+PFD and CD, respectively; n=31) were collected and subjected to single-cell RNA sequencing (scRNA-seq). Functional analyses were conducted using peripheral CD3+ T cells, intestinal tissue explants, primary fibroblasts and 2D-epithelial monolayer cell cultures. ResultsThe rectal mucosa of CD+PFD patients is imprinted with cellular and transcriptomic alterations specific to PFD and independent of luminal inflammation, potentially driven by TL1A activation in CD4+ T cells. We identified lymphotoxin beta (LTB or its functional heterotrimer LT1{beta}2) as a novel mediator downstream of TL1A that, along with IL-22, induces a PFD-associated signature in rectal fibroblast and epithelial cells, respectively. This signature includes an increased abundance of fibroblasts, an induction of matrix-degrading enzymes, transcriptomic rewiring of the lamina propria S1 fibroblasts, and an anti-bacterial and immune responses in epithelial cells. Notably, the induction of LT1{beta}2 and IL-22 occurs independently of TNF signaling, revealing a new TL1A-LT1{beta}2/IL-22 axis that remains active under anti-TNF therapy. ConclusionOur findings revealed unique cellular alterations in the rectum of CD patients with PFD, highlighting the previously unrecognized involvement of TL1A in mediating this signature and supporting the need for exploring the role of TL1A inhibition as a therapeutic approach for PFD.

immunology↗

bioRxiv2025

Single-cell multiomics identifies both shared and unique features of immune dysfunction in the colon, plasma and stool from individuals diagnosed with Parkinson's disease or inflammatory bowel disease

Parkinsons disease (PD) is the fastest growing neurodegenerative disease in the world1. Gastrointestinal (GI) dysfunction can occur decades before motor impairments and in up to 80% of individuals living with PD2,3,4. We investigated peripheral relationships that may underlie mechanisms along the gut-blood axis that contribute to PD pathogenesis. Single-cell multiomic spatial molecular imaging (SMI) of colonic tissue localized inflammatory injury within epithelial cells that appear to be associated with iron mishandling in both inflammatory bowel disease (IBD) and PD biosamples. We found that both the single-cell SMI of RNA and protein revealed parallel cross-modal dysregulation in the gut epithelium, in both IBD and PD biosamples. These data are accompanied by plasma (PD) and stool (IBD) protein depletion of CCL22. Our findings suggest iron mishandling along the gut barrier likely contributes to systemic inflammation, which may be the catalyst that primes circulating immune cells to body-first PD pathogenesis.

neuroscience↗

bioRxiv2024

Understanding the mechanisms underlying the lack of response to Janus kinase inhibition in ulcerative colitis

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon. About one-third of UC patients failed to respond to available drugs, including tofacitinib, a broad Janus kinase (JAK) inhibitor. However, the mechanisms underlying patient response or resistance to oral JAK inhibitors remain unknown. To elucidate the molecular and cellular pathways activated by tofacitinib in responder and non-responder patients, we generated a longitudinal single-cell RNA sequence dataset profiling both immune and non-immune cell populations from colonic biopsies of UC patients. Our analysis revealed that responders exhibited higher baseline JAK-STAT activity, while non-responders had increased baseline NF-kB pathway activation. Longitudinal comparisons showed that disease progression in non-responders was associated with increased abundance and enhanced activation of macrophages and fibroblasts. Our data suggest that resistance to tofacitinib is mediated by the hyperactivation of myeloid cells, and we identified IL-10-dependent macrophages as a cellular subset contributing to this resistance.

immunology↗

bioRxiv2024

Mitochondrial dysfunction: unraveling the elusive biology behind anti-TNF response during ulcerative colitis

BackgroundRecent studies hint at mitochondrial genes influencing UC patient response to anti-TNF treatment. We evaluated this hypothesis by following a targeted strategy to identify gene expression that captures the relationship between mitochondrial dysregulation and response to treatment. Our objective was to initially examine this relationship in colon samples and subsequently assess whether the resulting signal persists in the bloodstream. MethodsWe analyzed the transcriptome of colon samples from an anti-TNF treated murine model characterized by impaired mitochondrial activity and treatment resistance. We then transferred the findings that linked mitochondrial dysfunction and compromised treatment response to an anti-TNF treated UC human cohort. We next matched differential expression in the blood using monocytes from peripheral blood of controls and IBD patients, and we evaluated a classification process at baseline with whole blood samples from UC patients. ResultsIn human colon samples, the derived gene-set from the murine model showed differential expression, primarily enriched metabolic pathways, and exhibited similar classification capacity as genes enriching inflammatory pathways. Moreover, the evaluation of the classification signal using blood samples from UC patients at baseline highlighted the involvement of mitochondrial homeostasis in treatment response. ConclusionOur results highlight the involvement of metabolic pathways and mitochondrial homeostasis in determining treatment response and their ability to provide promising classification signals with detection levels in both colon and bloodstream.

immunology↗

bioRxiv2024

Music elicits different gene expression responses in the buccal cavity of age-related cognitive disorders patients and healthy controls

Recent evidence suggests that external stimuli can shape transcriptomes (sensogenomics). Specifically, the analysis of capillary blood samples has shown that musical stimuli can modulate gene expression patterns, in healthy individuals but also in those with age-related cognitive disorders (ACD), based on. Here, we present groundbreaking evidence indicating that brief exposure to music can also impact the salivary transcriptome in both healthy donors and ACD patients. Our findings reveal that music has a more pronounced effect on patients compared to controls, inducing global gene expression changes towards upregulation in ACD patients but downregulation in controls. The most significantly dysregulated genes in ACD patients include LGALS3 (downregulated) and CXCL8 (upregulated), whereas in controls, THOP1 was the top significant gene (downregulated). These genes play important roles in normal brain functions and are also altered in neurodegenerative conditions. Weighted Gene Co-expression Network Analysis reveals relevant and significant modules, both positive and negative correlated with music, implicated in neurodegenerative (e.g. autophagy) and immunological processes (e.g. IL-1, MHC). This sheds light on the complex interplay between music and molecular responses in the human body. This study underscores the potential of musical stimuli to influence gene expression patterns outside of systemic circulation, paving the way for further exploration of musics therapeutic effects. Sensogenomics Working GroupAntonio Salas Ellacuriaga - PI; Federico Martinon-Torres - PI; Laura Navarro Ramon - Coordinator GenPoB/GenVip - Instituto de Investigacion Sanitaria (IDIS) (alphabetic order)Alba Camino Mera, Albert Padin Villar, Alberto Gomez Carballa, Alejandro Perez Lopez, Alicia Carballal Fernandez, Ana Cotovad Bellas, Ana Isabel Dacosta Urbieta, Narmeen Mallah, Ana Maria Pastoriza Mourelle, Ana Maria Senin Ferreiro, Andres Muy Perez, Antia Rivas Oural, Antonio Justicia Grande, Antonio Pineiro Garcia, Anxela Cristina Delgado Garcia, Belen Mosquera Perez, Blanca Diaz Esteban, Carlos Duran Suarez, Carmen Curros Novo, Carmen Gomez Vieites, Carmen Rodriguez-Tenreiro Sanchez, Celia Varela Pajaro, Claudia Navarro Gonzalo, Cristina Seren Trasorras, Cristina Talavero Gonzalez, Eines Monteagudo Vilavedra, Estefania Rey Campos, Esther Montero Campos, Fernando Alvez Gonzalez, Fernando Caamano Vinas, Francisco Garcia Iglesias, Gloria Viz Rodriguez, Hugo Alberto Tovar Velasco, Irene Alvarez Rodriguez, Irene Garcia Zuazola, Irene Rivero Calle, Iria Afonso Carrasco, Isabel Ferreiros Vidal, Isabel Lista Garcia, Isabel Rego Lijo, Ivan Prieto Gomez, Ivan Quintana Cepedal, Jacobo Pardo Seco, Jesus Eiris Punal, Jose Gomez Rial, Jose Manuel Fernandez Garcia, Jose Maria Martinon Martinez, Julia Cela Mosquera, Julia Garcia Curras, Julian Montoto Louzao, Lara Martinez Martinez, Laura Navarro Marron, Lidia Pineiro Rodriguez, Lorenzo Redondo Collazo, Lua Castelo Martinez, Lucia Company Arciniegas, Luis Crego Rodriguez, Luisa Garcia Vicente, Manuel Vazquez Donsion, Maria Dolores Martinez Garcia, Maria Elena Gamborino Carames, Maria Elena Sobrino Fernandez, Maria Jose Curras Tuala, Maria Martinez Leis, Maria Soledad Vilas Iglesias, Maria Sol Rodriguez Calvo, Maria Teresa Autran Garcia, Marina Casas Perez, Marta Aldonza Torres, Marta Bouzon Alejandro, Marta Lendoiro Fuentes, Miriam Ben Garcia, Miriam Cebey Lopez, Montserrat Lopez Franco, Nour El Zahraa Mallah, Narmeen Mallah, Natalia Garcia Sanchez, Natalia Vieito Perez, Patricia Regueiro Casuso, Ricardo Suarez Camacho, Rita Garcia Fernandez, Rita Varela Estevez, Rosaura Picans Leis, Ruth Barral Arca, Sandra Carnota Antonio, Sandra Viz Lasheras, Sara Pischedda, Sara Rey Vazquez, Sonia Marcos Alonso, Sonia Seren Fernandez, Susana Rey Garcia, Vanesa Alvarez Iglesias, Victoria Redondo Cervantes, Vanesa Alvarez Iglesias, Wiktor Dominik Nowak, Xabier Bello Paderne, Xabier Mazaira Lopez Nursing volunteers (alphabetic order)Alejandra Fernandez Mendez, Ana Isabel Abadin Campana, Ana Maria Leon Caamano, Ana Maria Buide Illobre, Angeles Mera Cores, Carmen Nieves Vastro, Carolina Suarez Crego, Concepcion Rey Iglesias, Cristina Candal Regueira, Dolores Barreiro Puente, Elvira Rodriguez Rodriguez, Eugenia Gonzalez Budino, Eva Rey Alvarez, Fernando Rodriguez Gerpe, Gemma Albela Silva, Isabel Castro Perez, Isabel Dominguez Rios, Jose Angel Fernandez de la Iglesia, Jose Cruces Vazquez, Jose Luis Cambeiro Quintela, Jose Ramon Magarinos Iglesias, Julia Rey Brandariz, Julio Abel Fernandez Lopez, Luisa Garcia Vicente, Manuel Gonzalez Lito, Manuel Gonzalez Lijo, Manuela Perez Rivas, Margarita Turnes Paredes, Maria Aurora Mendez Lopez, Maria Begona Tome Arufe, Maria Campos Torres, Maria del Carmen Baloira Nogueira, Maria del Carmen Garcia juan, Maria Esther Moricosa Garcia, Maria Luz Chao Jarel, Maria Martinez Leis, Maria Mercedes Jimenez Santos, Maria Salome Buide Illobre, Maria Victoria Lopez Pereira, Mercedes Jorge Gonzalez, Mercedes Isolina Rodriguez Rodriguez, Miren Payo Puente, Natalia Carter Dominguez, Olga Maria Reyes Gonzalez, Pilar Mera Rodriguez, Purificacion Sebio Brandariz, Salome Quintans lago, Yolanda Rodriguez Taboada, Maria Pereira Grau. Other volunteers (alphabetic order)Alba Arias Gomez, Alejandro Moreno Diaz, Ana Arca Maran, Astro Gonzalez Guirado, Brais Garcia Iglesias, Carlos Sanchez Rubin, Carmen Otero de Andres, Clara Perez Errazquin Barrera, Claudia Rey Posse, Cristina Rojas Garcia, Eduardo Xavier Gimenez Bargiela, Elena Gloria Morales Garcia, Fabio Izquierdo Garcia Escribano, Gabriel Guisande Garcia, Jaime Lopez Martin, Lara Pais Ramiro, Lucia Rico Montero, Luis Estevez Martinez, Manuel Estevez Casal, Maria Aranzazu Palomino Cano, Maria Rubio Valdes, Marisol Nogales Benitez, Miryam Tilve Perez, Nuria Villar Muinos, Pablo Del Cerro Rodriguez, Pablo Pozuelo Martinez Cardenoso, Salma Ouahabi El Ouahabi, Santiago Vazquez Calvache

genomics↗

bioRxiv2023

Interpretable Inflammation Landscape of Circulating Immune cells

Inflammation is a biological phenomenon involved in a wide variety of physiological and pathological processes. Although a controlled inflammatory response is beneficial for restoring homeostasis, it can become unfavorable if dysregulated. In recent years, major progress has been made in characterizing acute and chronic inflammation in specific diseases. However, a global, holistic understanding of inflammation is still elusive. This is particularly intriguing, considering the crucial function of inflammation for human health and its potential for modern medicine if fully deciphered. Here, we leverage advances in the field of single-cell genomics to delineate the full spectrum of circulating immune cell activation underlying inflammatory processes during infection, immune-mediated inflammatory diseases and cancer. Our single-cell atlas of >6.5 million peripheral blood mononuclear cells from 1047 patients and 19 diseases allowed us to learn a comprehensive model of inflammation in circulating immune cells. The atlas expanded our current knowledge of the biology of inflammation of immune-mediated diseases, acute and chronic inflammatory diseases, infection and solid tumors, and laid the foundation to develop a precision medicine framework using unsupervised as well as explainable machine learning. Beyond a disease-centered analysis, we charted altered activity of inflammatory molecules in peripheral blood cells, depicting discriminative inflammation-related genes to further understand mechanisms of inflammation. Finally, we have laid the groundwork for developing precision medicine diagnostic tools for patients experiencing pathologic inflammation by learning a classifier for inflammatory diseases, presenting cells in circulation as a powerful resource for patient diagnosis.

immunology↗

bioRxiv2023

Tuning gene expression to music: the compensatory effect of music on age-related cognitive disorders

Extensive literature has explored the beneficial effects of music in age-related cognitive disorders (ACD), but limited knowledge exists regarding its impact on gene expression. We analyzed transcriptomes of ACD patients and healthy controls, pre-post a music session (n=60), and main genes/pathways were compared to those dysregulated in mild cognitive impairment (MCI) and Alzheimers disease (AD) as revealed by a multi-cohort study (n=1269 MCI/AD and controls). Music was associated with 2.3 times more whole-genome gene expression, particularly on neurodegeneration-related genes, in ACD than controls. Co-expressed gene-modules and pathways analysis demonstrated that music impacted autophagy, vesicle and endosome organization, biological processes commonly dysregulated in MCI/AD. Notably, the data indicated a strong negative correlation between musically-modified genes/pathways in ACD and those dysregulated in MCI/AD. These findings highlight the compensatory effect of music on genes/biological processes affected in MCI/AD, providing insights into the molecular mechanisms underlying the benefits of music on these disorders.

genomics↗

bioRxiv2023

FixNCut: Single-cell genomics through reversible tissue fixation and dissociation

The use of single-cell technologies for clinical applications requires disconnecting sampling from downstream processing steps. Early sample preservation can further increase robustness and reproducibility by avoiding artifacts introduced during specimen handling. We present FixNCut, a methodology for the reversible fixation of tissue followed by dissociation that overcomes current limitations. We applied FixNCut to human and mouse tissues to demonstrate the preservation of RNA integrity, sequencing library complexity, and cellular composition, while diminishing stress-related artifacts. Besides single-cell RNA sequencing, FixNCut is compatible with multiple single-cell and spatial technologies, making it a versatile tool for robust and flexible study designs.

bioinformatics↗