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PubMed2002

Analysis of a human brain transcriptome map.

BACKGROUND: Genome wide transcriptome maps can provide tools to identify candidate genes that are over-expressed or silenced in certain disease tissue and increase our understanding of the structure and organization of the genome. Expressed Sequence Tags (ESTs) from the public dbEST and proprietary Incyte LifeSeq databases were used to derive a transcript map in conjunction with the working draft assembly of the human genome sequence. RESULTS: Examination of ESTs derived from brain tissues (excluding brain tumor tissues) suggests that these genes are distributed on chromosomes in a non-random fashion. Some regions on the genome are dense with brain-enriched genes while some regions lack brain-enriched genes, suggesting a significant correlation between distribution of genes along the chromosome and tissue type. ESTs from brain tumor tissues have also been mapped to the human genome working draft. We reveal that some regions enriched in brain genes show a significant decrease in gene expression in brain tumors, and, conversely that some regions lacking in brain genes show an increased level of gene expression in brain tumors. CONCLUSIONS: This report demonstrates a novel approach for tissue specific transcriptome mapping using EST-based quantitative assessment.

Journal Article↗

PubMed2026

Targeting super-enhancer-driven SKIL transcription by CDK7 inhibitor THZ1 to suppress gastric cancer progression.

BACKGROUND: Gastric cancer (GC) is a lethal malignancy characterized by high incidence, mortality, and limited treatment options. Transcriptional addiction is a key cancer hallmark that drives tumor pathogenesis, making its inhibition a promising therapeutic strategy for GC. The study aims to investigate the roles and mechanisms of super-enhancer (SE)-driven oncogenic transcriptional addiction in GC progression and to identify novel targetable vulnerabilities. METHODS: We utilized cellular and animal models to assess the effects of THZ1 treatment and CDK7 knockdown on GC progression. RNA sequencing was employed to elucidate the potential molecular mechanism of THZ1 treatment. ChIP-seq was performed to establish SE landscape in GC. Integrative analysis of transcriptomic and SE profiling was used to identify THZ1-targeted oncogenic genes. Rescue experiments were conducted to confirm that THZ1 treatment suppresses GC malignant progression by targeting SE-driven SKIL transcription. RESULTS: GC cells exhibited pronounced sensitivity to THZ1 compared to normal gastric mucosa cells, and the treatment potently suppressed tumor growth and migration in both cellular and animal models. CDK7 was significantly upregulated in GC tissues, and its knockdown inhibited malignant progression in vitro and in vivo, whereas its overexpression accelerated tumor progression. Mechanistically, SE-driven oncogenic transcriptional amplification underlies GC cell susceptibility to THZ1, supported by the identification of novel oncogenic genes such as SKIL. SKIL, a key Hippo pathway regulator, was highly expressed in GC cells, and its elevated expression predicted poor patient prognosis. SKIL silencing attenuated malignant phenotypes, while its overexpression diminished THZ1’s suppression of GC cell proliferation and migration. CONCLUSION: Our findings demonstrate that THZ1 inhibits GC progression by disrupting SE-driven oncogenic transcription, thereby offering CDK7 inhibition as a promising therapeutic intervention for GC.

Stomach Neoplasms↗

PubMed2026

Inheritance of the epigenetic signature and reduced intermuscular bone phenotype acquired via DNA methylation editing of the runx2 b promoter in zebrafish.

The presence of intermuscular bones (IBs) can directly affect the economic value of aquaculture fish. Although genome editing can create IB-free fish by knocking out key IB-related genes, such as runx2b, the associated DNA sequence alterations raise food safety and health concerns, limiting its breeding applications. In this study, we used CRISPR/dCas9-mediated epigenome-editing technology targeting the runx2 b promoter in zebrafish to alter DNA methylation patterns without changing the DNA sequence. Our results showed that higher runx2 b promoter methylation patterns significantly inhibited eGFP mRNA expression levels in the recombinant plasmid. Using the CRISPR/dCas9-Dnmt7 system to enhance methylation of the zebrafish runx2b promoter, we observed a significant decrease in runx2 b mRNA expression levels in the F0 generation. The IBs in the 11 th-16 th muscle segments of the adult F0 fish were significantly shorter compared with the controls. Inbreeding of fish was used to produce F1 and F2 offspring that retained these high promoter methylation levels, along with persistent runx2b expression suppression and IB development inhibition. Transcriptome sequencing analysis suggested that increasing runx2 b promoter methylation levels may synergistically induce additional epigenetic modifications, potentially affecting the PPAR signaling pathway and FoxO transcription factor regulation, which appears to inhibit osteoblast proliferation and differentiation. Overall, this study demonstrates an innovative application of epigenetic editing technology for aquaculture breeding. By precisely regulating the expression patterns of key genes for economically important traits while preserving genomic DNA integrity, this approach provides a theoretical foundation and technical support for improving fish economic traits.

Animals↗

PubMed2026

Comprehensive characterization of the genes in AP2/ERF family and their involvement in salt-alkali stress response during Nelumbo nucifera seed germination.

Nelumbo nucifera Gaertn. is an economically and ecologically important aquatic plant, but its growth and productivity are severely constrained by soil salinization and alkalization. AP2/ERF transcription factors are key regulators of plant abiotic stress responses; however, their roles in salt-alkali tolerance in N. nucifera remain largely unclear. In this study, we performed a genome-wide identification and characterization of the AP2/ERF gene family in N. nucifera, followed by phylogenetic, structural, and physicochemical analyses. A total of 101 AP2/ERF genes were identified and classified into five subfamilies, showing both evolutionary conservation and species-specific divergence compared with Arabidopsis thaliana. Physiological analyses during seed germination under salt-alkali stress revealed significant changes in malondialdehyde content, proline accumulation, and antioxidant enzyme activities, suggesting activation of oxidative stress defense and osmotic adjustment mechanisms. Transcriptome profiling of seedlings treated with 150 mM salt-alkali solution for 5 and 10 days identified 7,350 differentially expressed genes, including 29 AP2/ERF members responsive to stress. Among them, 13 genes, including AP2-9, ERF23, ERF15, ERF31, ERF34, and DREB21, were consistently upregulated under both treatments, indicating their potential roles in stress adaptation. qRT-PCR validation further confirmed the sustained upregulation of key genes AP2-9, ERF23, ERF34, and DREB21, consistent with transcriptome data. Overall, this study provides the first comprehensive overview of the AP2/ERF gene family in N. nucifera and identifies candidate regulators involved in salt-alkali stress responses, offering valuable insights into the molecular mechanisms of stress adaptation and potential genetic resources for breeding salt-alkali tolerant aquatic plants.

AP2/ERF transcription factors↗

PubMed2003

The antigen processing machinery of class I human leukocyte antigens: linked patterns of gene expression in neoplastic cells.

The ultimate outcome of an immune response (escape or surveillance) depends on a delicate balance of opposing signals delivered by activating and inhibitory immune receptors expressed by cytotoxic T lymphocytes and natural killer cells. In this light, loss and down-regulation of human leukocyte antigens (HLA) class I molecules, while important for keeping tumors below the T-cell detection levels, may incite recognition of missing self. Conversely, the maintenance of normal levels of expression (or even up-regulation) may be favorable to tumors, at least in certain cases. In this study, we took advantage of a previously characterized panel of 15 early passage tumor cell lines (mainly from melanoma and lung carcinoma lesions) enriched with class I-low phenotypes. These cells were systematically characterized by Northern and/or Western blotting (e.g., mini-transcriptome/mini-proteome analysis) for the expression of HLA-A, -B, -C, beta(2)-microglobulin, and the members of the "antigen processing machinery" of class I molecules (LMP2, LMP7, TAP1, TAP2, tapasin, calreticulin, calnexin, and ERp57). In addition, we established four pairs of cultures, each comprising melanoma cells and normal melanocytes from the same patient. We found that approximately 97% of the 185 tested gene products are expressed (although often weakly), and in many cases coordinately regulated in 18 of 19 tumor cell lines. Linked expression patterns could be hierarchically arranged by statistical methods and graphically described as a class I HLA "coordinome." Deviations (both down- and up-regulation) from the coordinome expression pattern inherited from the normal, paired melanocyte counterpart, were allowed but limited in magnitude, as if melanoma cells were trying to keep a "low profile" HLA phenotype. We conclude that irreversible HLA loss is a rare event, and class I expression in tumor cells almost invariably results from reversible gene regulatory (rather than gene disruption) events.

Antigens, Neoplasm↗

PubMed2003

Granular gland transcriptomes in stimulated amphibian skin secretions.

Amphibian defensive skin secretions are complex, species-specific cocktails of biologically active molecules, including many uncharacterized peptides. The study of such secretions for novel peptide discovery is time-limited, as amphibians are in rapid global decline. While secretion proteome analysis is non-lethal, transcriptome analysis has until now required killing of specimens prior to skin dissection for cDNA library construction. Here we present the discovery that polyadenylated mRNAs encoding dermal granular gland peptides are present in defensive skin secretions, stabilized by endogenous nucleic acid-binding amphipathic peptides. Thus parallel secretory proteome and transcriptome analyses can be performed without killing the specimen in this model amphibian system--a finding that has important implications in conservation of biodiversity within this threatened vertebrate taxon and whose mechanistics may have broader implications in biomolecular science.

Alternative Splicing↗

PubMed2026

High-throughput single-cell proteomics and transcriptomics from same cells with a nanoliter-scale, spin-transfer approach.

Single-cell multiomic platforms provide a comprehensive snapshot of cellular states and cell types by offering critical insights into the spatiotemporal regulation of biomolecular networks at a systems level, thereby defining the basis of multicellularity. Here, we introduce nanoSPINS, an advanced platform that enables high-throughput profiling and integrative analysis of the transcriptome and proteome from the same single cells using RNA sequencing and isobaric labeling LC-MS-based proteomics, respectively. NanoSPINS can efficiently transfer mRNA-containing droplets across two microarrays via a centrifugation-based approach, while proteins are retained on the initial platform. Benchmarking of nanoSPINS on two cell lines demonstrates its ability to generate global proteomic and transcriptomic profiles that align well with previously established methodologies/platforms. The incorporation of isobaric TMTpro labeling into this single-cell multiomics platform significantly enhances the throughput of single-cell proteomic analyses. Through the high-throughput quantification of the proteome and transcriptome, nanoSPINS not only facilitates the identification of molecular features at both mRNA and protein level but also provides larger sample sizes for improved statistical power in clustering and differential abundance. Given the broad applicability of single-cell multiomics in biological research and clinical settings, we believe nanoSPINS represents a powerful platform for the characterization of heterogeneous cell populations.

Single-Cell Analysis↗

PubMed2025

A genome-wide association study identifies a novel East Asian-specific locus for dementia with Lewy bodies in Japanese subjects.

BACKGROUND: Dementia with Lewy bodies (DLB) is the second most common type of degenerative dementia in older patients. As with other multifactorial diseases, the pathogenesis results from interactions of environmental and genetic factors. The genetic basis of DLB is not yet fully understood. Recent genomic analyses of DLB in Caucasian cohorts identified genetic susceptibility loci for DLB, but the comprehensive genomic analysis in Asians was still not performed. METHODS: We conducted a genome-wide association study (GWAS) in Japanese subjects (211 DLB cases and 6113 controls) to clarify the genetic architecture of DLB pathogenesis. RESULTS: We identified the East Asian-specific DHTKD1 locus (rs138587229) on chromosome 10 with genome-wide significance (GWS; P = 3.2710-8) and the ICOS/PARD3B locus on chromosome 2 with suggestive significance (P = 3.9510-7) as novel DLB genetic risk loci. We also confirmed the APOE locus (rs429358, P < 5.0 × 10-8), a known risk locus for DLB and Alzheimer's disease in Caucasians. The DHTKD1 locus was associated with the gene expression of SEC61A2 and showed a causal relationship with cholinesterase levels. In a trans-ethnic meta-analysis that included Japanese, UK Biobank, and other Caucasian GWAS, we confirmed the risk for DLB at APOE and SNCA loci with GWS. Transcriptome-wide association analysis identified ZNF155 and ZNF284 in the brain cortex and GPRIN3 in the substantia nigra as putative causal genes for DLB. CONCLUSIONS: This is the first GWAS for DLB in East Asians, and our findings provide new biological and clinical insights into the pathogenesis of DLB.

Aged↗

PubMed2002

Genomics and plant cells: application of genomics strategies to Arabidopsis cell biology.

In this review I seek to describe how the complete catalogue of plant genes and proteins, revealed by genome sequencing, can provide novel insights into cell biology. Many new analytical methods have been developed to digest the flood of genome sequence data, including analysis of the transcriptome, proteome and metabolites. High-throughput analysis of protein targeting and other methods will ascribe new information to proteins and create important links with other large datasets. To fulfil the potential revealed by this genomic information, many challenges have to be met. Among these are organizational changes needed to create common datasets accessible to all scientists, and bioinformatics solutions to capture and integrate diverse datasets. Once harnessed, these new strategies will irrevocably change the way we conduct plant science.

Arabidopsis↗

PubMed2026

Machine learning-integrated multi-omics risk prediction for pulmonary fungal infection in COPD and lung cancer: a transcriptomic and immune profiling study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and lung cancer are major risk factors for invasive pulmonary fungal infection (IPFI), carrying an attributable mortality of 30%-80%. Their coexistence further amplifies immunosuppression, while current diagnostic criteria remain inadequate for early risk identification. METHODS: Transcriptomic data from the GEO dataset GSE296912 (scRNA-seq; 12,078 cells from normal and COPD lung tissue) and The Cancer Genome Atlas (TCGA)-lung adenocarcinoma (LUAD) bulk RNA-seq cohort (539 tumor and 59 normal samples) underwent differential expression and cross-omics integration analysis. Five machine learning models were constructed: logistic regression, SVM, random forest, XGBoost, and LASSO. Candidate genes were validated by qRT-PCR in A549 cells and THP-1-derived macrophages stimulated with heat-inactivated Aspergillus fumigatus conidia, a protocol selected to ensure BSL-2 biosafety compliance and isolate PAMP-mediated innate immune signaling. Model performance was evaluated using 5-fold stratified cross-validation with AUC, calibration curves, and decision curve analysis. RESULTS: Single-cell transcriptomic analysis of 12,078 cells identified 14 distinct cell populations, with marked myeloid expansion and immune dysregulation in COPD lung tissue. Cross-omics integration with TCGA-LUAD data identified 1,145 shared genes (79 immune-related), converging on NF-κB, TLR4, and cytokine receptor signaling. The random forest model achieved excellent discriminative performance (5-fold CV AUC = 0.988), with Treg infiltration, TLR4, and MMP9 as the top predictors. qRT-PCR confirmed significant upregulation of all five candidate genes (DEFB4A, S100A8, IL-8, MMP9, and TLR4) in both A549 and THP-1 cells following fungal stimulation. CONCLUSION: This multi-omics machine learning model integrating scRNA-seq and TCGA transcriptomic data demonstrates excellent discriminative performance (AUC = 0.988), with mechanistic convergence of NF-κB, TLR4, and oncogenic signaling pathways identified across shared immune gene signatures. In vitro qRT-PCR validation confirms the biological relevance of five key antifungal immune genes, providing a transcriptomic foundation for future prospective IPFI risk stratification in patients with COPD and lung cancer.

TLR4↗

PubMed2025

Longitudinal Multi-Organ Transcriptomic Atlas of Salt-Induced Hypertension.

BACKGROUND: Salt-sensitive hypertension is a prevalent and clinically significant subtype of hypertension, where increased dietary salt intake elevates blood pressure and causes injury to multiple organ systems. Despite extensive research, dynamic molecular changes and conserved versus organ-specific transcriptional programs in hypertensive multi-organ damage remain poorly understood. Defining complex molecular pathways both in a temporal sequence and in an organ-specific manner is essential for developing targeted, precision therapies to mitigate hypertensive disease burden. METHODS: We generated a longitudinal multi-organ transcriptomic atlas of salt-sensitive hypertension using RNA sequencing of kidney cortex, kidney medulla, heart, and liver from Dahl salt-sensitive rats across four disease stages. A comprehensive bioinformatic analysis mapped dynamic transcriptional programs, evaluated 50 biological pathways, and defined upstream regulators. Histological and biochemical assays complemented transcriptomic analysis, while integration with human genome-wide association studies (GWAS) and compound-transcriptome analysis provided translational insights and identified candidate therapeutics. RESULTS: Salt-induced hypertension elicited both shared and tissue-specific transcriptional programs that evolved with disease progression. The kidney medulla showed robust early immune activation with metabolic suppression, while the cortex exhibited transient metabolic activation before declining and initiating immune activation. The liver and heart showed time-dependent metabolic and inflammatory remodeling. Cross-organ comparisons revealed a shared early proliferative response that converged on proinflammatory and fibrotic signatures. Upstream regulator analysis identified 79 time- and tissue-specific transcription factors associated with gene expression dynamics. GWAS integration analysis revealed endocrine signaling, ion transport, lipid metabolism, and detoxification as conserved pathways across species, underscoring the translational relevance of the model and study. Predictive compound-transcriptome analyses identified kinase inhibitors targeting phosphoinositide 3-kinase, mechanistic target of rapamycin and cyclin-dependent kinases as top candidates to counteract maladaptive transcriptional programs. CONCLUSIONS: This study defines temporal and tissue-specific transcriptomic remodeling in salt-sensitive hypertension and highlights the need for precision interventions to prevent progressive organ damage.

Journal Article↗

PubMed2001

Human mast cell transcriptome project.

After draft reading of the human genome sequence, systemic analysis of the transcriptome (the whole transcripts present in a cell) is progressing especially in commonly available cell types. Until recently, human mast cells were not commonly available. We have succeeded to generate a substantial number of human mast cells from umbilical cord blood and from adult peripheral blood progenitors. Then, we have examined messenger RNA selectively transcribed in these mast cells using high-density oligonucleotide probe arrays. Many unexpected but important transcripts were selectively expressed in human mast cells. We discuss the results obtained from transcriptome screening by introducing our data regarding mast-cell-specific genes.

Blood Cells↗

PubMed2026

Transcriptomics reveals species-specific adaptive strategies to calorie restriction in two Argopecten scallops with distinct lifespans.

Calorie restriction (CR) is a well-established non-genetic intervention for lifespan extension in multiple model organisms. Seasonal food shortage in cold and temperate seas may mimic CR, inducing in bivalves a response similar to that in vertebrates and thereby prolonging life expectancy. However, the relationship and the mechanism underlying the food availability and lifespan in bivalves remain largely unexplored. Two closely related scallop species the short-lived warm-water Argopecten irradians (lifespan <2 years) and the longer-lived cold-water Argopecten purpuratus (7-10 years) provide an ideal comparative system to investigate species-specific adaptive strategies. In this study, we subjected both species to CR for 30 and 56 days and performed comparative transcriptomic profiling, weighted gene co-expression network analysis (WGCNA), and physiological assays to elucidate their distinct molecular responses. Transcriptomic analysis revealed that A. purpuratus exhibited substantially more DEGs than A. irradians at both time points under CR, with both species showing downregulation of metabolic pathways but to different extents. A. irradians mounted an early nutrient-sensing response at 30 days (IGF1R, PIK3R3, INSR suppression), indicating acute sensitivity to limitation; by contrast, A. purpuratus displayed delayed FoxO activation at 56 days, along with its downstream effectors NFKBIA, CREB3L4, and SMAD4, suggesting a gradual adaptive program may link to its extended lifespan. WGCNA identified three negatively correlated modules in each species, with coral2 being the most prominent in A. irradians and darkolivegreen in A. purpuratus. The former was dominated by ciliary motility genes, whereas the latter featured coordinated repression of oxidative phosphorylation. Additionally, both species exhibited conserved suppression of mTOR/S6K growth signaling and activation of cellular maintenance programs. Collectively, these findings expand the understanding of CR-mediated longevity regulation in bivalves and provide candidate gene resources for future functional studies and breeding programs.

Pectinidae↗

PubMed2025

Proteomic hub proteins CDKN2B, TRAPPC2L, WFS1, and ARPP19 drive biochemical recurrence and metastatic progression in prostate cancer: Protein macromolecule action.

The biological characteristics and metastasis mechanism of prostate cancer are complex, involving the important role of many proteins in cell transcriptional regulation. This study focused on the role of the proteomic hub proteins CDKN2B, TRAPPC2L, WFS1 and ARPP19 in the biochemical recurrence and metastasis progression of prostate cancer. Cross-platform transcriptome integration and differential expression analysis were used to evaluate transcriptome characteristics in a prostate cancer cohort. Functional enrichment analysis was performed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation, and weighted gene co-expression network analysis (WGCNA) was used to investigate cancer progression subtypes. It was found that prostate cancer progression showed significant transcriptome heterogeneity, and low-expression genes dominated. We reveal the important role of epithelial-immune interactions and inflammatory signaling in transcriptional remodeling in prostate cancer. The co-expression network topology analysis showed that the immune-metabolic center module plays a central role in cancer progression. CDKN2B was identified as a key transcriptional determinant in prostate cancer typing, while TRAPPC2L and WFS1 acted as core transcriptional regulators, driving metastatic heterogeneity. ARPP19 and LOC650152 also show important transcriptional driving effects in advanced prostate cancer.

Humans↗

PubMed2026

Integrative genomic and transcriptomic analyses identify key regulators of skin pigmentation in Larimichthys crocea.

The yellow body coloration of large yellow croaker (Larimichthys crocea) constitutes a crucial economic trait, yet its underlying genetic regulatory mechanisms remain poorly understood. This study systematically elucidated the molecular basis of body color variation by integrating genome resequencing and skin transcriptome analyses, combined with the contextual analysis of key pigmentation-related genes and phenotypic histological validation. 200 phenotyped individuals (including yellow-selected lines, F1 progeny, and normal control groups, all derived from a well-characterized aquaculture stock) identified 39 significantly associated SNPs (-log₁₀(P) ≥ 6), mapping to multiple candidate genes. These genes were significantly enriched in pathways related to pigment deposition (GO:0033059), melanosome organization (GO:0032438), melanogenesis, and tyrosine metabolism. Cross-developmental stage transcriptome analysis revealed 2395 differentially expressed genes (DEGs). Multi-omics integration identified eight overlapping candidate genes, including tyrp1, slc45a2, oca2, and dgat2, among which tyrp1 was prioritized for in-depth validation based on its core regulatory role in eumelanin synthesis, significant SNP association signal, and consistent downregulation in transcriptomic data. Experimental validation demonstrated that the g.895C > T mutation in exon 2 of tyrp1b was strongly significantly associated with the yellow phenotype: the frequency of mutant genotypes (TT/CT) reached 92.86%in the yellow-selected group, whereas the control group exclusively exhibited the wild-type genotype (CC). qPCR confirmed significantly downregulated tyrp1b expression in the skin of yellow individuals, consistent with the transcriptome trend. Histological and stereomicroscopic observations of skin tissues further validated the physiological basis of the yellow phenotype, revealing a significant reduction in melanophore number and abnormal melanosome morphology in yellow-phenotype individuals, accompanied by increased xanthophore density. These results suggest that tyrp1b mutation is strongly associated with the yellow phenotype. However, the presence of a wild-type CC individual in the yellow group indicates that this mutation is not strictly required for yellow coloration, suggesting that other genetic or environmental factors may also contribute to the phenotype, Additionally, downregulation of the carotenoid metabolism gene bco2 coupled with upregulation of xdh, together with the functional changes of slc45a2 and oca2, may synergistically promote xanthophore pigment deposition, contributing to the yellow phenotype. As melanin synthesis in large yellow croaker relies on the conserved tyrosinase pathway and transporter proteins, mutations in associated genes (tyrp1b, slc45a2, oca2) represent a primary underlying cause for the loss of melanin-based coloration and transition to a yellow phenotype in L. crocea. These findings provide key molecular targets and a theoretical foundation for molecular breeding of body color in this species, and also enrich the understanding of xanthism regulatory mechanisms in teleosts.

Animals↗

PubMed2026

NextLongIso: a comprehensive Nextflow pipeline for multi-dimensional long-read RNA-seq analysis.

SUMMARY: Long-read RNA sequencing technologies, including Pacific Biosciences (PacBio) and Oxford Nanopore Technologies (ONT), enable direct characterization of full-length transcripts and transcriptome complexity. However, analysis of long-read RNA-seq data remains fragmented across multiple tools, limiting the ability to obtain a unified view of transcript structure, expression, and regulatory variation in long-read transcriptomes. We present NextLongIso, a scalable and reproducible Nextflow pipeline that enables coordinated analysis of multiple layers of transcript regulation. Rather than focusing solely on transcript reconstruction, NextLongIso integrates transcript discovery with downstream regulatory analyses to jointly characterize alternative splicing, isoform switching, transcript boundary dynamics (including alternative promoters and polyadenylation), and transposable element-associated transcription from both PacBio and ONT datasets. By eliminating complex cross-tool data harmonization, this unified framework facilitates the transition from transcript identification to functional interpretation of transcriptomic variation. AVAILABILITY AND IMPLEMENTATION: NextLongIso is implemented in Nextflow and is freely available at github: https://github.com/YidanSunResearchLab/nf-LongIso.git and Zenodo: https://doi.org/10.5281/zenodo.21049837.

Software↗

PubMed2026

Integrative transcriptomic, spatial and functional-genomic analysis identifies a UFMylation-related vascular-stromal program and prioritizes WWTR1 in glioblastoma.

Glioblastoma (GBM) contains spatially organized stress-adaptive and vascular niches. Because transcript abundance does not measure UFM1 conjugation, we asked whether a UFMylation-related transcriptional axis identifies a reproducible tissue program and alters candidate prioritization. In 518 unique primary TCGA-GBM tumors profiled on the Affymetrix HT Human Genome U133A array, weighted gene co-expression network analysis of 8,000 variable genes yielded 12 modules. The 278-gene green module ranked first across nine prespecified traits (mean |r|=0.637). Direct overlap comprised 1/3 measurable UFMylation-core, 5/19 ER-stress/UPR, and 2/15 proteostasis genes; after excluding overlapping genes, correlations with the green eigengene remained significant (r = 0.373, 0.831, 0.639, and 0.699 for UFMylation-core, ER-stress/UPR, proteostasis, and composite scores, respectively). The green score was associated with overall survival per standard-deviation increase (HR 1.17, 95% CI 1.07-1.28), although clinical adjustment attenuated the estimate. In a 10-sample single-cell dataset, sample-level scores were higher in pericytes and endothelial cells than in malignant cells. Donor-aware IvyGAP analysis supported regional organization, whereas one Visium section showed stronger concordance with ER-stress/UPR and mesenchymal scores than with the UFMylation-core score. CellChat indicated pathway-selective rather than global remodeling of inferred vascular communication. Layer ablation moved WWTR1 from rank 48 using WGCNA alone to rank 4 overall and rank 1 among non-common-essential genes after cross-platform integration. These findings define an ER-stress/mesenchymal-weighted, UFMylation-related vascular-stromal transcriptional association and nominate WWTR1 for experimental testing.

Humans↗

PubMed2026

highSpaClone enables copy number alteration inference and tumor subclone analysis for high-resolution spatial transcriptomics.

High-resolution spatially resolved transcriptomics (SRT) offers unprecedented opportunities to investigate tumor heterogeneity but poses substantial computational and analytical challenges. Here, we present highSpaClone, a computational framework for copy number alteration (CNA) inference and tumor subclone identification from high-resolution SRT data across multiple spatial scales. By integrating spatial constraints into CNA estimation and clonal clustering, highSpaClone enables neighboring spatial locations to share information, thereby improving the robustness of genomic signals and the accuracy of subclone delineation. Across multiple Xenium and Visium HD datasets, highSpaClone revealed unique transcriptional programs, clonal evolutionary trajectories, and distinct tumor-microenvironment interactions. Furthermore, in human colorectal cancer samples, highSpaClone detected CNA events in histologically normal epithelial regions, highlighting early genomic alterations associated with field cancerization. These findings establish highSpaClone as a scalable framework for studying clonal architecture and tumor evolution.

CP: cancer biology↗