Neuropsychiatric disorders are complex conditions influenced by genomic variants that alter gene expression and RNA isoforms. A study utilized a novel bioinformatic pipeline, IsoLamp, in conjunction with nanopore long-read amplicon sequencing to profile the RNA isoform repertoire of 31 high-confidence neuropsychiatric disorder risk genes in the human brain. This comprehensive analysis revealed significant insights into how these genes contribute to disease risk through altered expression and splicing (ref: De Paoli-Iseppi doi.org/10.1186/s13059-025-03724-1/). Another study focused on frontotemporal dementia (GRN-FTD), employing single-nuclei long-read RNA sequencing to investigate splicing dysregulation in glial and neuronal cells. This research highlighted the complexity of exon dysregulation linked to TDP-43 pathology, revealing cell-type-specific splicing alterations that may underlie neurodegeneration (ref: Belchikov doi.org/10.1016/j.celrep.2025.116198/). Additionally, the cataloging of Cacna1e splice variants using long-read sequencing provided insights into the functional diversity of voltage-gated calcium channels, emphasizing the potential impact of alternative splicing on channel function (ref: Bhuiyan doi.org/10.1186/s12864-025-11887-1/). Together, these studies underscore the critical role of RNA isoforms in neuropsychiatric disorders and the need for advanced sequencing techniques to elucidate their complexities.

Long-read sequencing has emerged as a powerful tool for understanding complex genomic structures and transcriptomic landscapes. The integration of nanopore sequencing with a bioinformatic pipeline, IsoLamp, allowed for an in-depth profiling of RNA isoforms associated with neuropsychiatric disorders, revealing the intricate relationships between genomic variants and gene expression (ref: De Paoli-Iseppi doi.org/10.1186/s13059-025-03724-1/). Another significant advancement was the introduction of single-nuclei long-read RNA sequencing, which provided a detailed view of splicing dysregulation in frontotemporal dementia, showcasing the technique's ability to resolve complex cellular contexts and highlight specific dysregulations in neuronal and glial cells (ref: Belchikov doi.org/10.1016/j.celrep.2025.116198/). Furthermore, the development of SKiM, a metagenomic classifier designed for Oxford Nanopore reads, addresses the challenges of classification accuracy and memory efficiency, indicating the ongoing evolution of long-read sequencing technologies to meet diverse research needs (ref: Schneggenburger doi.org/10.1093/bioinformatics/). The application of long-read sequencing in studying polyadenylation dynamics during long-term potentiation in the rat brain further emphasizes its versatility, revealing critical insights into mRNA regulation during synaptic plasticity (ref: Gumińska doi.org/10.1261/rna.080485.125/).

Methylation profiling has emerged as a crucial tool in the diagnosis of central nervous system (CNS) tumors, particularly in cases complicated by prior radiation therapy. A case report highlighted the utility of a conserved methylation signature in accurately predicting the nature of a heavily irradiated CNS tumor, which presented with perplexing histopathological features. This case underscores the importance of molecular diagnostics in enhancing the accuracy of tumor classification, especially when traditional histological methods may be confounded by treatment effects (ref: Handoko doi.org/10.3892/br.2025.2043/). The findings suggest that integrating methylation profiling into routine diagnostic workflows could significantly improve patient outcomes by facilitating timely and accurate treatment decisions.

Transcranial Direct Current Stimulation (tDCS) and Transcranial Magnetic Stimulation (TMS) are two neuromodulatory techniques that have shown promise in treating various neurological disorders. A comparative transcriptomic analysis aimed to elucidate the long-term effects of tDCS in relation to immediate effects and the long-term impacts of TMS. By generating a novel dataset and leveraging publicly available data, the study revealed that both tDCS and TMS may engage similar biological pathways, although their immediate and enduring effects on gene expression may differ (ref: Agrawal doi.org/10.3390/ijms26178634/). This research highlights the potential for tDCS to induce lasting changes in brain function, suggesting that further exploration of its molecular mechanisms could enhance therapeutic strategies in neuromodulation.

The regulation of local protein synthesis through cytoplasmic polyadenylation is critical for synaptic maintenance and plasticity. A study utilizing nanopore sequencing investigated the polyadenylation landscape during long-term potentiation (LTP) in the rat hippocampus, providing insights into mRNA 3'-end dynamics and poly(A) tail lengths. The findings revealed significant alterations in transcriptomic responses associated with LTP, suggesting that polyadenylation plays a vital role in the molecular mechanisms underlying synaptic plasticity (ref: Gumińska doi.org/10.1261/rna.080485.125/). This research contributes to a deeper understanding of how mRNA regulation influences neuronal function and highlights the importance of polyadenylation in the context of learning and memory.