Biology subjects

Diaz, A. A.

Publications and source records attributed to Diaz, A. A..

2 recordsLinked to original sources

bioRxiv2025

Validation of bronchial airway gene expression associated with bronchiectasis in nasal epithelium

ObjectivesExamination of bronchial epithelium-derived gene expression signature of bronchiectasis (BE) in nasal epithelium. MethodsWe studied 220 participants from the Detection of Early Lung Cancer Among Military Personnel study with bulk RNA-seq of nasal epithelium brushings. Gene set enrichment analysis (GSEA) was used to examine whether genes previously identified as increased or decreased in the bronchial epithelium of individuals with radiologic BE are significantly enriched among the genes most significantly altered in the nasal epithelium. GSEA and cell-type specific gene expression signatures were used to examine changes in the cellular composition of nasal epithelium associated with radiologic BE. ResultsGenes previously found to have significantly altered expression in bronchial epithelium in radiologic BE are concordantly enriched among the genes most increased or decreased in nasal epithelium in radiologic BE in this validation set (p = 3x10-7, increased; p = 6x10-8, decreased). GSEA performed using cell-type signatures demonstrates that in nasal epithelium, BE is associated with increased multiciliated and deuterosomal cell-related gene expression and decreased expression of basal cell- related gene expression, consistent with our previous findings in bronchial epithelium. ConclusionOur work validates our bronchial signature of BE in an independent dataset and demonstrates that similar gene expression changes are associated with radiologic BE in the bronchial and nasal epithelium. These findings support considering nasal epithelium brushing as a less invasive tool for screening and monitoring BE. SummaryThis study validates a previously reported bronchial signature of bronchiectasis (BE) in nasal epithelium. Changes in gene expression and cell-type composition associated with radiologic BE are similar across both bronchial and nasal epithelium.

bioinformatics↗

bioRxiv2023

Challenges in the discovery of tumor-specific alternative splicing-derived cell-surface antigens in glioma

BackgroundDespite advancements in cancer immunotherapy, solid tumors remain formidable challenges. In glioma, profound inter-and intra-tumoral heterogeneity of antigen landscape hampers therapeutic development. Therefore, it is critical to consider alternative sources to expand the repertoire of targetable (neo-)antigens and improve therapeutic outcomes. Accumulating evidence suggests that tumor-specific alternative splicing (AS) could be an untapped reservoir of neoantigens. ResultsIn this study, we investigated tumor-specific AS events in glioma, focusing on those predicted to generate major histocompatibility complex (MHC)-presentation-independent, cell-surface neoantigens that could be targeted by antibodies and chimeric antigen receptor (CAR)-T cells. We systematically analyzed bulk RNA-sequencing datasets comparing 429 tumor samples (from The Cancer Genome Atlas [TCGA]) and 9,166 normal tissue samples (from the Genotype-Tissue Expression project [GTEx]), and identified 13 AS events in 7 genes predicted to be expressed in more than 10% of the patients, including PTPRZ1 and BCAN, which were corroborated by an external RNA-sequencing dataset. Subsequently, we validated our predictions and elucidated the complexity of the isoforms using full-length transcript amplicon sequencing on patient-derived glioblastoma cells. However, analyses of the RNA-sequencing datasets of spatially mapped and longitudinally collected clinical tumor samples unveiled remarkable spatiotemporal heterogeneity of the candidate AS events. Furthermore, proteomics analysis did not reveal any peptide spectra matching the putative neoantigens. ConclusionsOur investigation illustrated the diverse characteristics of the tumor-specific AS events and the challenges of antigen exploration due to their notable spatiotemporal heterogeneity and elusive nature at the protein levels. Redirecting future efforts toward intracellular, MHC-presented antigens could offer a more viable avenue.

cancer biology↗