GEO 数据集

主题由标题与摘要自动归类；样本量为数据集标注之和，SuperSeries 可能与其 SubSeries 重复计算。

• HNRNPH2-R114W remodels RNA splicing and neurodevelopmental gene programs in isogenic cerebral organoids
  GSE348913Homo sapiens4 个样本2026-10-31

  Autism spectrum disorder has been linked to disrupted RNA processing during corticogenesis, yet variant-specific mechanisms remain difficult to resolve. Isogenic cerebral organoids derived from a patient-derived induced pluripotent stem cell (iPSC) line carrying the HNRNPH2-R114W variant and its CRISPR-corrected counterpart serve as a human developmental model to investigate variant-associated RNA dysregulation. Imaging quantification and exploratory bulk RNA sequencing, performed at a single developmental time point using one pooled organoid RNA sample from each genotype, identify coordinated remodeling of neuronal and metabolic programs, along with junction-centered splicing dysregulation involving 6,310 differentially used junctions. Computational structural docking situates HNRNPH2 RNA recognition motifs (RRMs) 1-3 within a spliceosomal context and locates residue R114 near a predicted RNA-contact interface, indicating that the R114W substitution may alter RNA engagement. Integration of differential expression with event- and isoform-level analyses identifies regulatory hubs enriched for axon guidance and synaptic signaling pathways. Single-cell-reference-based deconvolution suggests modest compositional shifts that are unlikely to account for the extent of transcriptional and splicing alterations observed. Collectively, these findings implicate HNRNPH2-R114W in widespread RNA rewiring and define candidate isoform-level endpoints for mechanistic and therapeutic investigation in human cortical organoids. These molecular signatures open new avenues to examine how HNRNPH2-associated RNA dysregulation evolves across developmental time and recurs across independent biological contexts, providing a foundation for further mechanistic studies of this rare neurodevelopmental disorder.

  单细胞计算与 AI
• GOLDEN: Gene expression and allele-informed decomposition for genetic heterogeneity in spatial transcriptomic data
  GSE341398Homo sapiens2 个样本2026-10-31

  Spatial transcriptomics (ST) enables exploration of cellular interactions, but current methods rely on pathologist annotation and face limitations in addressing genetic heterogeneity, where niches harbor non-clonal cells, as in placental or allograft tissues. To decipher such inter-individual heterogeneity in ST, we developed GOLDEN (Gene expression and allele-informed decomposition for genetic heterogeneity), an allele-aware multi-task network that encodes spot-level expression into shared latent representations. Incorporating allele features, it uses dual heads to classify spot identity (target, non-target, or mixed) and to estimate target fractions. For evaluation, we generated synthetic ST data via a Gamma-distribution model using semi-allogeneic single-cell profiles. On these synthetic benchmarks, GOLDEN achieved reliable deconvolution (Pearson's r = 0.977; MAE = 0.045) while maintaining consistent predictions across real-world STs, which were validated through genetic evidence.

  单细胞空间转录组计算与 AI
• Detection of a sequence feature for recursive splicing
  GSE327295Homo sapiens5 个样本2026-10-30

  RNA splicing is directed by cis-acting sequence signals interacting with trans-acting factors to remove introns from newly transcribed pre-mRNA, joining exons to generate mature mRNA. Splicing happens far more often than observed exon-exon junctions in mRNA. As one contributing process, the spliceosome progressively removes large introns in small segments by ‘recursive splicing’, instead of splicing the whole intron at one time. However, the cis-acting sequences associated with recursive splicing have not been identified. Using probabilistic mixture models, we found that recursive splicing occurs more frequently in first introns, which are typically longer, and exhibit a distinct CG-rich sequence feature in the sequences flanking the upstream 5’SS, and depletion of CGs in the downstream polypyrimidine tract. Remarkably, recursive splicing is also more frequent in downstream introns of genes containing first introns with these properties. Mechanistically, these data suggest that early events in RNA synthesis and processing influence the prevalence of recursive splicing for the rest of the transcript. Finally, we developed a sequence-dependent classifier for recursive splicing, which we tested with a novel medium-throughput primer extension assay. In summary, the usage of recursive splicing sites is established at the beginning of RNA synthesis through newly-identified sequence motifs flanking both ends of the first intron.

  计算与 AI
• Lamin B1 physically regulates neuronal migration by modulating nuclear deformability in the developing cortex
  GSE347519Mus musculus18 个样本2026-10-29

  Neuronal migration positions billions of neurons to form a functional brain. Effective navigation through the cortex requires precise regulation of nuclear mechanics in migrating neurons. We demonstrate that Lamin B1 (LB1) regulates neuronal migration by modulating nuclear deformability. Elevated LB1 in neurons halted migration in vivo, without affecting laminar identity or pre-migratory gene expression. Mispositioned neurons subsequently caused electrophysiological defects in the brain. In vitro, increased LB1 raised nuclear stiffness, as measured by atomic force microscopy, and reduced neuronal motility in confined environments reconstituted with microchambers. Computational modeling predicted a temporal link between nuclear deformation and increased migration velocity, which was validated experimentally through live imaging. Notably, cerebral organoid assays using induced pluripotent stem cells established from patients with LMNB1 duplication exhibited impaired neuronal migration in a human model. Collectively, these findings establish LB1 as a critical regulator of nuclear mechanics, ensuring accurate spatiotemporal positioning of neurons.

  计算与 AI
• Novel WRN Exon 10 Skipping Mutation Triggers Progerin Accumulation and Premature Aging
  GSE351663Mus musculus6 个样本2026-10-26

  Werner Syndrome (WS) is an autosomal recessive disorder characterized by premature aging and increased susceptibility to various age-related diseases, predominantly caused by mutations in the WRN gene. This study investigated a Chinese patient with WS and partial lipoatrophic diabetes mellitus, aiming to identify a novel pathogenic variant in the WRN gene. High-throughput sequencing was conducted on genomic DNA from a blood sample. The identified homozygous variant (WRN_intron9 c.1270-1G>C) was confirmed, and its pathogenicity was assessed through in silico predictions, structural modeling, and cell function assays. The variant's effect on exon skipping was analyzed, and cellular assays were performed to validate the induced phenotype. The study identifies a novel WRN variant as a potential pathogenic factor in the patient. Simulations predict that the WRN_intron9 c.1270-1G>C mutation triggers exon 10 skipping, deleting one of the two highly homologous peptide regions encoded by exon 10 and exon 11 respectively. Cellular assays confirm senescent phenotype induction and human progerin accumulation, leading to premature cellular senescence.

  计算与 AI
• A GABA-producing Limosilactobacillus fermentum ameliorates autism-like behaviors associated with altered gut microbial metabolism and cortical GABA signaling
  GSE351532Mus musculus24 个样本2026-10-26

  Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by social deficits and restricted, repetitive behaviors. Altered excitation/inhibition (E/I) balance, including impaired γ-aminobutyric acid (GABA) ergic signaling, has been implicated as a key pathophysiological feature of ASD. Although growing evidence implicates the gut–brain axis in regulating neural function, the strain-specific microbial mechanisms that influence central GABAergic signaling remain incompletely understood. Here, we evaluated whether Limosilactobacillus fermentum IMB064, identified by genome-based in silico screening, could modulate ASD-associated symptoms in BTBR mice, a widely used ASD model. Oral administration of IMB064 significantly reduced repetitive behaviors and improved social novelty preference in BTBR mice. Taxa-resolved metabolic flux modeling of the gut microbiome based on metagenomic profiling indicated that IMB064 administration was associated with alterations in gut microbial metabolic potential, including increased potential for GABA production, particularly among GABA-producing taxa such as Limosilactobacillus. Transcriptomic analysis further revealed a cortex-selective response to IMB064, with 1,552 cortical genes significantly altered and enriched in neuronal signaling pathways. These differentially expressed genes significantly overlapped with human ASD-associated cortical co-expression modules identified by weighted gene co-expression network analysis (WGCNA) and with chromatin-regulatory gene networks. Consistent with this region-specific molecular response, IMB064 significantly increased cortical GABA levels, with a trend toward an increased GABA-to-glutamate ratio, whereas no significant changes were observed in the striatum. Collectively, these findings indicate that the GABA-producing strain IMB064 alters gut microbial metabolic potential and is associated with cortex-selective changes in GABA-related neurochemical profiles, accompanied by modulation of human ASD-relevant gene networks and improvement of ASD-like behavioral phenotypes, supporting IMB064 as a promising live biotherapeutic candidate for ASD.

  计算与 AI
• Gene Expression Data of Neuroendocrine Tumors from Different Primary Sites
  GSE305904Homo sapiens194 个样本2026-10-26

  Neuroendocrine tumors (NETs) represent a unique group of tumors with diverse anatomical origins but share common clinical and molecular characteristics. Despite their low mutational burden and limited number of recurrent mutations, epigenetic mechanisms play a crucial role in their biology. This study aims to establish a universal molecular classification of NETs, independent of their site of origin, by integrating gene expression and methylation data. The objective is to uncover shared vulnerabilities to support the development of improved diagnostic, prognostic, and predictive biomarkers, as well as innovative treatment strategies to enhance patient outcomes. Transcriptomic and methylomic profiles were examined from paraffin-embedded tumor samples of 194 patients diagnosed with G1-G3 neuroendocrine tumors (NETs) originating in the gastrointestinal-pancreatic (GEP) tract and lungs. Using these integrated datasets, a Multi-Omics Factor Analysis (MOFA) model comprising eight factors was developed. This model facilitated the application of unsupervised clustering algorithms, resulting in a consensus molecular classification for neuroendocrine tumors.

  多组学计算与 AI