Biology subjects

Mallah, N. E. Z.

Publications and source records attributed to Mallah, N. E. Z..

5 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

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↗

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↗

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↗