Music compensates for altered gene expression in 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 Alzheimer's 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 in 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.

Sensogenomics of music and Alzheimer's disease: An interdisciplinary view from neuroscience, transcriptomics, and epigenomics.

Introduction: The relationship between music and Alzheimer's disease (AD) has been approached by different disciplines, but most of our outstanding comes from neuroscience. Methods: First, we systematically reviewed the state-of-the-art of neuroscience and cognitive sciences research on music and AD (>100 studies), and the progress made on the therapeutic impact of music stimuli in memory. Next, we meta-analyzed transcriptomic and epigenomic data of AD patients to search for commonalities with genes and pathways previously connected to music in genome association, epigenetic, and gene expression studies. Results: Our findings indicate that >93% of the neuroscience/ cognitive sciences studies indicate at least one beneficial effect of music on patients with neurodegenerative diseases, being improvements on memory and cognition the most frequent outcomes; other common benefits were on social behavior, mood and emotion, anxiety and agitation, quality of life, and depression. Out of the 334 music-related genes, 127 (38%) were found to be linked to epigenome/transcriptome analysis in AD (vs. healthy controls); some of them (SNCA, SLC6A4, ASCC2, FTH1, PLAUR and ARHGAP26) have been reported to be associated e.g. with musical aptitude and music effect on the transcriptome. Other music-related genes (GMPR, SELENBP1 and ADIPOR1) associated to neuropsychiatric, neurodegenerative diseases and music performance, emerged as hub genes in consensus co-expression modules detected between AD and music estimulated transcriptomes. In addition, we found connections between music, AD and dopamine related genes, with SCNA being the most remarkable - a gene previously associated with learning and memory, and neurodegenerative disorders (e.g., Parkinson's disease and AD). Discussion: The present study indicate that the vast majority of neuroscientific studies unambiguously show that music has a beneficial effect on health, being the most common benefits relevant to Alzheimer's disease. These findings illuminate a new roadmap for genetic research in neurosciences, and musical interventions in AD and other neurodegenerative conditions.

Role and Diagnostic Performance of Host Epigenome in Respiratory Morbidity after RSV Infection: The EPIRESVi Study.

Background: Respiratory syncytial virus (RSV) infection has been associated with the subsequent development of recurrent wheezing and asthma, although the mechanisms involved are still unknown. We investigate the role of epigenetics in the respiratory morbidity after infection by comparing methylation patterns from children who develop recurrent wheezing (RW-RSV), subsequent asthma (AS-RVS), and those experiencing complete recovery (CR-RSV). Methods: Prospective, observational study of infants aged < 2 years with RSV respiratory infection admitted to hospital and followed-up after discharge for at least three years. According to their clinical course, patients were categorized into subgroups: RW-RSV (n = 36), AS-RSV (n = 9), and CR-RSV (n = 32). The DNA genome-wide methylation pattern was analyzed in whole blood samples, collected during the acute phase of the infection, using the Illumina Infinium Methylation EPIC BeadChip (850K CpG sites). Differences in methylation were determined through a linear regression model adjusted for age, gender and cell composition. Results: Patients who developed respiratory sequelae showed a statistically significant higher proportion of NK and CD8T cells (inferred through a deconvolution approach) than those with complete recovery. We identified 5,097 significant differentially methylated positions (DMPs) when comparing RW-RSV and AS-RVS together against CR-RSV. Methylation profiles affect several genes involved in airway inflammation processes. The most significant DMPs were found to be hypomethylated in cases and therefore generally leading to overexpression of affected genes. The lead CpG position (cg24509398) falls at the gene body of EYA3 (P-value = 2.77×10-10), a tyrosine phosphatase connected with pulmonary vascular remodeling, a key process in the asthma pathology. Logistic regression analysis resulted in a diagnostic epigenetic signature of 3-DMPs (involving genes ZNF2698, LOC102723354 and RPL15/NKIRAS1) that allows to efficiently differentiate sequelae cases from CR-RSV patients (AUC = 1.00). Enrichment pathway analysis reveals the role of the cell cycle checkpoint (FDR P-value = 4.71×10-2), DNA damage (FDP-value = 2.53×10-2), and DNA integrity checkpoint (FDR P-value = 2.56×10-2) in differentiating sequelae from CR-RSV patients. Conclusions: Epigenetic mechanisms might play a fundamental role in the long-term sequelae after RSV infection, contributing to explain the different phenotypes observed.

A multi-tissue study of immune gene expression profiling highlights the key role of the nasal epithelium in COVID-19 severity.

Coronavirus Disease-19 (COVID-19) symptoms range from mild to severe illness; the cause for this differential response to infection remains unknown. Unravelling the immune mechanisms acting at different levels of the colonization process might be key to understand these differences. We carried out a multi-tissue (nasal, buccal and blood; n = 156) gene expression analysis of immune-related genes from patients affected by different COVID-19 severities, and healthy controls through the nCounter technology. Mild and asymptomatic cases showed a powerful innate antiviral response in nasal epithelium, characterized by activation of interferon (IFN) pathway and downstream cascades, successfully controlling the infection at local level. In contrast, weak macrophage/monocyte driven innate antiviral response and lack of IFN signalling activity were present in severe cases. Consequently, oral mucosa from severe patients showed signals of viral activity, cell arresting and viral dissemination to the lower respiratory tract, which ultimately could explain the exacerbated innate immune response and impaired adaptative immune responses observed at systemic level. Results from saliva transcriptome suggest that the buccal cavity might play a key role in SARS-CoV-2 infection and dissemination in patients with worse prognosis. Co-expression network analysis adds further support to these findings, by detecting modules specifically correlated with severity involved in the abovementioned biological routes; this analysis also provides new candidate genes that might be tested as biomarkers in future studies. We also found tissue specific severity-related signatures mainly represented by genes involved in the innate immune system and cytokine/chemokine signalling. Local immune response could be key to determine the course of the systemic response and thus COVID-19 severity. Our findings provide a framework to investigate severity host gene biomarkers and pathways that might be relevant to diagnosis, prognosis, and therapy.

RNA-Seq Data-Mining Allows the Discovery of Two Long Non-Coding RNA Biomarkers of Viral Infection in Humans.

There is a growing interest in unraveling gene expression mechanisms leading to viral host invasion and infection progression. Current findings reveal that long non-coding RNAs (lncRNAs) are implicated in the regulation of the immune system by influencing gene expression through a wide range of mechanisms. By mining whole-transcriptome shotgun sequencing (RNA-seq) data using machine learning approaches, we detected two lncRNAs (ENSG00000254680 and ENSG00000273149) that are downregulated in a wide range of viral infections and different cell types, including blood monocluclear cells, umbilical vein endothelial cells, and dermal fibroblasts. The efficiency of these two lncRNAs was positively validated in different viral phenotypic scenarios. These two lncRNAs showed a strong downregulation in virus-infected patients when compared to healthy control transcriptomes, indicating that these biomarkers are promising targets for infection diagnosis. To the best of our knowledge, this is the very first study using host lncRNAs biomarkers for the diagnosis of human viral infections.