SEARCH · PubMed Health

Results for “comparative transcriptomics”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 253 records · Page 14Linked to original sources

PubMed2025

CountASAP: a lightweight, easy to use python package for processing ASAPseq data.

BACKGROUND: Declining sequencing costs coupled with the increasing availability of easy-to-use kits for the isolation of DNA and RNA transcripts from single cells have driven a rapid proliferation of studies centered around genomic and transcriptomic data. Simultaneously, a wealth of new techniques have been developed that utilize single cell technologies to interrogate a broad range of cell-biological processes. One recently developed technique, transposase-accessible chromatin with sequencing (ATAC) with select antigen profiling by sequencing (ASAPseq), provides a combination of chromatin accessibility assessments with measurements of cell-surface marker expression levels. While software exists for the characterization of these datasets, there currently exists no tool explicitly designed to reformat ASAP surface marker FASTQ data into a count matrix which can then be used for these downstream analyses. RESULTS: To address this lack of a dedicated tool for ASAPseq data processing, we created CountASAP, an easy-to-use Python package purposefully designed to transform FASTQ files from ASAP experiments into count matrices compatible with commonly-used downstream bioinformatic analysis packages. CountASAP takes advantage of the independence of the relevant data structures to perform fully parallelized matches of each sequenced read to user-supplied input ASAP oligos and unique cell-identifier sequences. We directly compare the performance and user-friendliness of CountASAP to existing tools using similarly-structured data from a more common sequencing experiment: cellular indexing of transcriptomes and epitopes by sequencing (CITEseq). Further benchmarking against existing tools helps to identify proper defaults for CountASAP and assess the agreement of outputs from all tested software. A final test using a novel ASAPseq dataset provides evidence that CountASAP can generate biologically meaningful results that correlate well with paired chromatin accessibility data. CONCLUSIONS: CountASAP shows good agreement with existing, well-tested data processing tools in the analysis of similarly-structured benchmarking data. CountASAP runs efficiently on a standard laptop, has user-friendly documentation, a one-step installation, and represents the first and only tool designed specifically for the processing of ASAPseq data.

Software↗

PubMed2026

Nuclear export inhibition activates TP53 pathways and is a potent therapeutic strategy in atypical teratoid rhabdoid tumors.

BACKGROUND: Atypical teratoid/rhabdoid tumor (ATRT) is an aggressive central nervous system tumor mostly affecting young children. Improved and less toxic therapies for children with ATRT are imperative due to the toxicities associated with current treatments. Furthermore, existing therapies do not address the underlying genetic drivers of ATRT. In this study, we sought to determine whether exportin-1 (XPO1) is a genetic dependency and therapeutic target in ATRT. METHODS: We utilized an integrative approach harnessing patient-derived ATRT cell lines, functional genomics, pharmacologic assays, transcriptomics, and in vivo intracranial xenograft models to systematically test the hypothesis that XPO1 is a novel dependency in ATRT. RESULTS: Analysis of RNA-sequencing datasets revealed high XPO1 expression in ATRT cells compared to other pediatric brain tumor cell lines. Both CRISPR/Cas9 genetic knockdown and pharmacologic inhibition of XPO1 using 6 selective inhibitors of nuclear export (SINEs) in patient-derived atypical teratoid/rhabdoid tumor (ATRT) cells led to significant reduction in cell viability and proliferation. Furthermore, we observed increased apoptosis, G0 phase cell cycle arrest, and upregulation of TP53 signaling pathways in cells treated with the SINE selinexor. Consistently, our transcriptomic data revealed the upregulation of apoptosis and TP53 signaling pathways and concomitant depletion of cell cycle gene sets. In vivo, selinexor in combination with radiation and cyclophosphamide led to significant reduction in tumor volume and increased animal survival in intracranial ATRT xenograft models. CONCLUSIONS: Our data reveals XPO1 as a novel genetic dependency and potent therapeutic target in ATRT.

atypical teratoid rhabdoid tumor↗

PubMed2026

Amaryllidaceae Alkaloids and Isoquinoline Alkaloids: A Perspective on Historical Approaches to Pathway Elucidation.

Alkaloid biosynthesis is a central topic in plant specialized metabolism because many alkaloids have ecological, pharmacological, and biotechnological relevance. Isoquinoline alkaloids (IAs) and Amaryllidaceae alkaloids (AAs) are both connected to aromatic amino acid metabolism, but they differ in taxonomic distribution, scaffold-forming chemistry, pathway resolution, and biotechnological development. This review compares the historical and methodological trajectories that have shaped IA and AA pathway elucidation, from compound isolation, radiotracer experiments, and biochemical inference to transcriptomics, metabolomics, functional enzymology, isotope-guided active-tissue identification, regulatory studies, and heterologous pathway reconstruction. In IAs, especially benzylisoquinoline alkaloids, broad genomic and transcriptomic resources have supported candidate gene discovery and functional characterization of several branches, including morphinan, protoberberine, benzophenanthridine, and aporphine-related pathways. In contrast, AA biosynthesis has advanced more recently through function-driven approaches that clarified key steps such as N4OMT-mediated 4'-O-methylation, NBS/NR-mediated norbelladine formation, CYP96T-dependent regioselective oxidative coupling, and transient reconstruction of major scaffold-forming branches. Remaining gaps include the unresolved enzymatic formation of 3,4-dihydroxybenzaldehyde in AAs and incomplete functional validation across less-studied IA scaffold classes. By integrating biochemical logic, omics-guided discovery, enzyme evolution, tissue specificity, regulation, and synthetic biology, this review identifies priorities for future alkaloid pathway discovery and sustainable production.

3,4-dihydroxybenzaldehyde↗

PubMed2026

Proteogenomic features define subtypes of mantle cell lymphoma.

Mantle cell lymphoma (MCL) is a biologically heterogeneous B-cell malignancy. Although genomics and transcriptomics have delineated parts of the MCL disease spectrum, proteomics remains largely unexplored. Here, we conducted a comprehensive proteogenomic analysis integrating genomics, transcriptomics, and proteomics on peripheral blood samples from 27 patients with MCL and 4 healthy donors to investigate the translational and posttranslational dimensions of MCL. Our study identified 1296 downregulated and 468 upregulated proteins in MCL cells. The splicing pathways were significantly upregulated at both the mRNA and protein levels, suggesting a critical role for aberrant RNA splicing in MCL pathogenesis. Integration of proteomic data with genetic aberrations revealed immunoglobulin heavy chain variable mutational status and CCND1 mutation are associated with distinctive transcriptomic and proteomic profiles, which correspond to significant differences in clinical outcomes. A multiomics molecular stratification model incorporating proteomic data showed superior predictive power for patient survival compared with single-omics models (concordance index, 0.83 vs 0.74). This study provides, to our knowledge, the first comprehensive proteogenomic profile of MCL, offering novel insights into its molecular mechanisms and clinical behavior. The identification of molecular subtypes and prognostic protein signatures underscores the potential of proteomics to guide precision medicine strategies for MCL.

Humans↗

PubMed2026

Dual-transcriptomic analysis of human nasal transcriptome and microbiome reveals host-bacteria associations in symptomatic respiratory infection.

BACKGROUND: The human nasopharynx is colonized by a diverse community of commensal microbiota linked to many respiratory diseases, yet their associations with the host remain unclear. RESULTS: In this study, we introduced a dual-transcriptomics analysis strategy, which can characterize the host transcriptome and microbiome from nasal samples simultaneously. We applied this workflow to a local SARS-CoV-2 cohort with 76 asymptomatic infected patients, among whom 52 (68.42%) developed symptomatic infection during a 1-week follow-up period. Nasal swabs were collected from all 76 patients at enrollment and from 73 patients at one-week later follow-up. We detected a median of 8.94% reads that did not map to the human genome across all 149 samples, among which around half (median 49.68%) were successfully mapped to microbiome genome. Meta-transcriptomic analysis detected significantly higher SARS-related coronavirus loads in samples from the symptomatic group at enrollment (P = 0.004), and both groups showed decreased loads one week later (symptomatic, P = 0.001; asymptomatic, P = 0.035). Compared with benchmarking 16 S rRNA sequencing on 53 samples, our computational strategy showed high correlation of relative abundance in all top 20 genera (median Rho = 0.90, Pmax < 0.001). A total of 670 bacteria species were identified to show a relative abundance ≥ 0.01% in at least 10% samples. Differential abundance analysis identified 76 species (DASs) from six phyla with significantly decreased abundance in samples from the symptomatic group (log2(fold change or FC) < -1 and adjusted P < 0.05) compared to the asymptomatic group at enrollment. Integrating these symptom-associated DASs with host's gene expression using an expression quantitative trait bacteria (eQTB) model, we found 45 symptom-associated DASs identified at enrollment were significantly associated with one to 14 genes (adjusted P < 0.05). GSEA showed a series of symptom-associated DASs were significantly correlated with pathways related to olfactory function, keratinocyte differentiation, and DNA methylation. CONCLUSIONS: In summary, our dual-transcriptomic analysis strategy effectively characterized host-microbiome associations, offering insights into microbial contributions to respiratory diseases.

Humans↗

PubMed2026

Loss of Function Dnmt3a Mutation Leads to Aberrant Neutrophil Migration.

Clonal hematopoiesis (CH), an age-related expansion of somatically mutated hematopoietic clones, is associated with increased risk of severe infections including coronavirus disease (COVID)-19, yet the underlying mechanisms remain unclear. Here, we investigated the impact of Dnmt3a deficiency in a murine model of influenza A virus (IAV) pneumonia. Dnmt3a-deficient mice exhibited increased pulmonary viral burden and reduced neutrophil accumulation in IAV-infected lungs despite comparable circulating neutrophil numbers. Functional analyses of neutrophils showed impaired chemotactic migration in vitro, whereas maturation, antimicrobial enzyme content, and metabolic capacity were unchanged. Transcriptomic profiling revealed downregulation of pathways involved in chemotaxis, cytokine signaling, and cellular activation, including reduced expression of Cxcr1. Supporting the translational relevance of these findings, proteomic analysis of plasma from individuals with germline DNMT3A mutations (Tatton-Brown-Rahman syndrome) revealed alterations in proteins associated with cell migration and cytoskeletal dynamics. Collectively, our findings demonstrate that Dnmt3a loss compromises innate immune defense by impairing neutrophil migration in a cell-intrinsic manner, leading to ineffective pathogen clearance. This work provides mechanistic insight into how CH-associated mutations contribute to age-associated susceptibility to infection and highlights altered leukocyte trafficking as a potential therapeutic target in aging populations with CH.

Animals↗

PubMed2025

Deleterious, protein-altering variants in GSPT2 are putatively associated with an X-linked neurodevelopmental disorder with intellectual disability, language impairment, autism, and epilepsy.

PURPOSE: Approximately 6% of individuals with neurodevelopmental disorders are predicted to be X-linked, and the GSPT2 gene, located at Xp11.22, has not yet been associated with any Mendelian disease. METHODS: To establish genotype-phenotype associations between GSPT2 and neurodevelopmental disorders, clinical investigations were performed in unrelated individuals, genomic and functional studies were conducted on the participants' blood and heterologous cell system. RESULTS: We described 6 individuals from 6 unrelated families carrying hemizygous variants in GSPT2 with intellectual disability, delayed speech and language development, autism spectrum disorder, epilepsy, or abnormal fetal neurodevelopment. Structural molecular modeling revealed significant deleterious effects of the identified variants. GSPT2 is preferentially enriched in the brain and cerebellum compared with other tissues. GSPT2-deficient H4 neuroglioma cells slow down the proliferation and downregulate the expression of cell-cycle-related genes. Transcriptomics revealed that GABAergic and calcium-signaling-related genes were significantly downregulated in GSPT2-deficient cells. Consistent with the transcriptomic data, RT-PCR analysis verified the marked downregulation of critical genes (CACNA1B, etc) in GSPT2-knockout cells and further confirmed these findings with proteomic profiling. CONCLUSION: Our data suggest a putative GSPT2-related X-linked neurodevelopmental disorders through dysregulation of cell-cycle progression and calcium/GABAergic signaling pathways.

Humans↗

PubMed2025

Intratumoral fungus Neurospora crassa is associated with worsened prognosis in ovarian cancer via modulation of extracellular matrix.

Landmark studies on intratumoral fungi (ITF) have raised concerns due to irreproducible results and data-analysis errors. We aimed to determine whether ITF exist in ovarian cancer (OvCa) and, if so, whether they play a role in disease biology. Formalin-fixed, paraffin-embedded OvCa samples and multiple controls underwent operational decontamination, qPCR, internal transcribed spacer sequencing, and post-hoc data decontamination. We also leveraged updated fungal reads from The Cancer Genome Atlas generated by the TCMbio group, which addressed human-read contamination and artificial inflation, to validate findings and assess prognostic associations. A murine syngeneic model established using mouse ovarian cancer cell line (OVHM) with intratumoral Neurospora crassa injection was established. Transcriptomic and metabolomic analyses were performed to explore mechanisms. Tumor-containing blocks harbored significantly higher fungal loads than environmental controls but had loads comparable to paraffin controls. Applying a two-pass decontamination filter reduced raw sequence features from 9289 amplicon sequence variants (ASVs) to 659 ASVs. We focused on high-abundance features present in human tissues but absent from xenografts and paraffin controls and identified one candidate, N. crassa, associated with unfavorable prognosis in OvCa. Integrating human and murine data, we found Neurospora correlated with eosinophils, whereas N. crassa itself was not immune-related. Neurospora crassa promoted OvCa progression with downregulation of integrin-linked kinase and decreased extracellular matrix-receptor interaction. Most ITF signals are likely contaminants. We identified N. crassa as associated with unfavorable prognosis in OvCa, potentially via modulation of the extracellular matrix.

Neurospora crassa↗

PubMed2025

Hepatocyte dedifferentiation in 2D culture reveals extensive transcriptomic and proteomic rewiring.

BACKGROUND: Primary hepatocytes are commonly used in vitro to model liver metabolism, but prolonged culturing results in dedifferentiation and potentially limits the applicability of this model. METHODS: We characterized the transcriptome and proteome of full liver and primary hepatocytes as either freshly isolated cells or after 24 hours of 2D-culturing. RESULTS: We found that 2D-culturing for 24 hours changes more than 10,000 genes and 3000 proteins compared with freshly isolated cells, accompanied by a decrease in transcriptional heterogeneity and a loss of zonal markers. Moreover, there were changes in proteins associated with the extracellular matrix, in mitochondrial and ribosomal protein abundances, as well as an increase in the abundance of acute-phase response proteins. CONCLUSION: Collectively, primary mouse hepatocytes in culture rewire the transcriptome and proteome, which may affect the utility of this model to study physiological and molecular mechanisms related to the liver. We developed the Shiny app "Hepamorphosis" (https://cbmr.ku.dk/research/resources/shiny-apps/), which allows users to explore RNA/protein correlations, zonation profiles, and cell-type-specific transcription in full liver and cultured hepatocytes.

Hepatocytes↗

PubMed2025

The skeletal muscle of aged male mice exhibits sustained growth regulatory transcriptional profile following glucocorticoid exposure compared with young males.

Excess glucocorticoids induce skeletal muscle myopathy by changing gene expression. Advanced age augments glucocorticoid-mediated muscle phenotypes, yet the transcriptional responses underlying those augmented phenotypes are unclear. The purpose of this study was to define the glucocorticoid-responsive transcriptome in young and aged muscle following both acute and more prolonged glucocorticoid treatment. Young (4-mo-old) or aged (24-mo-old) male mice were administered either an acute injection of dexamethasone (DEX) or vehicle or daily DEX or vehicle injections for 7 days. Muscles were harvested 6.5 h after the final or only injection. The tibialis anterior (TA) was selected for RNA sequencing analysis as DEX treatment lowered TA mass specifically in aged males. In silico analyses identified enriched pathways and transcription factors predicted to regulate DEX-sensitive genes. Acute DEX altered similar numbers of genes in young (950) versus aged males (913), although aged males had greater magnitudes of fold change. After 7 days of DEX treatment, aged muscle exhibited more DEGs compared with acute exposure (1,196 vs. 913), whereas young muscle exhibited fewer DEGs than after acute exposure (599 vs. 950). In aged males, glucocorticoid-sensitive genes were consistently enriched for growth regulatory processes across both time points, a pattern that was not evident in young males. Despite those age-associated transcriptional differences, the transcription factors predicted to regulate the glucocorticoid-sensitive genes were similar in young and aged males. These data expand our understanding into how aging modifies the transcriptional response to excess glucocorticoids in skeletal muscle.NEW & NOTEWORTHY Glucocorticoids promote mass loss in certain muscles with advanced age but not at younger ages. In a muscle whose mass is lost in response to elevated glucocorticoids only in advanced age in males, we show that glucocorticoids initiate a unique and exaggerated transcriptional profile after both acute exposure to the hormone and after prolonged treatment that is consistent with muscle atrophy. These findings expand our understanding of the effect primary aging has on glucocorticoid-induced atrophy in males.

Animals↗

PubMed2026

Evolutionary Reorganization of Transcriptomic Architecture Across a UVB Tolerance Gradient in Fish.

Environmental stressors such as ultraviolet radiation impose strong selective pressures on organisms, yet how adaptation to such stressors shapes transcriptomic responses at the network level remains poorly understood. Although stratospheric ozone is recovering globally, substantial regional variation in UV exposure persists, particularly in high-altitude environments where extreme UV levels can occur. Here, we compared three fish models representing distinct biological responses to UVB exposure: wild-type zebrafish (Danio rerio), a melanin-deficient zebrafish mutant (nacre) lacking a major protective mechanism against UVB damage, and the high-altitude Andean killifish Orestias ascotanensis, a species naturally exposed to extreme UVB radiation. Together, these models define a gradient spanning physiological protection, impaired protection, and evolutionary adaptation to UVB stress. Using RNA-seq and protein-protein interaction networks, we show that transcriptomic responses differ markedly across this gradient. Wild-type and nacre zebrafish exhibited relatively limited transcriptomic changes (∼2%-2.4% of genes changing), whereas O. ascotanensis displayed a large-scale and highly coordinated response (∼21.6% of genes changing) characterized by functionally specialized networks enriched in DNA repair pathways. These differences involved not only transcriptomic magnitude but also marked reorganization of transcriptomic architecture. Integration with positive selection analyses revealed that positively selected genes were concentrated within highly interconnected regions of transcriptomic networks, consistent with adaptation involving network reorganization. Furthermore, ortholog-based analyses suggest that adaptive responses involve differential reorganization of a conserved functional background. Together, our results support a model in which adaptation to environmental stress is associated with the reorganization of conserved transcriptomic networks across physiological and evolutionary contexts, providing a systems-level perspective on the molecular basis of adaptation.

UVB radiation↗

PubMed2026

Wound healing in Atlantic spiny dogfish sharks.

Field observations and limited experimental studies indicate that elasmobranchs can repair substantial skin injuries, but the temporal course and cellular composition of wound healing in Atlantic spiny dogfish remain poorly characterized. We conducted an exploratory laboratory study in 20 female Atlantic spiny dogfish (Squalus acanthias) using standardized full-thickness skin wounds monitored by serial photography for 35 days, histological analysis at defined post-injury time points, and pooled single-nucleus RNA sequencing of intact and wounded skin. A continuous neoepithelial layer covered all examined wound beds by Day 1, whereas macroscopic wound area decreased progressively over 35 days and dermal denticles remained absent from the repaired surface. Histological examination showed progressive neoepidermal maturation, basement-membrane reformation, collagen deposition, and granulation-tissue organization, indicating that epithelial coverage preceded restoration of normal skin architecture. Single-nucleus RNA sequencing identified epithelial, stromal, vascular, pigment, neural, and immune-cell populations. T and B cells were detected in intact skin, and their relative abundance, together with that of several other leukocyte populations, increased at Day 1 and generally declined by Day 14. Because samples were pooled by time point, these transcriptomic changes are descriptive. These findings characterize rapid early reepithelialization followed by slower tissue remodeling in Atlantic spiny dogfish and provide a foundation for future comparative studies of elasmobranch skin repair.

Animals↗

PubMed2026

TNIK Overexpression Is Sufficient for Chemoradiation Resistance in Limited-Stage Small Cell Lung Cancer.

Small cell lung cancer (SCLC) is characterized by early metastasis, intrinsic chemoradiation resistance, and tumor recurrence. Besides the lack of potentially targetable oncogenic drivers, therapeutic advancements are also hindered by the scarcity of surgically resected tissue specimens ideal for profiling studies. We used patient-derived xenografts (PDX) to model SCLC chemoradiation resistance and identified chemoradiation resistance candidate genes using RNA sequencing. Additionally, we used human SCLC cell lines to confirm our in vivo results and delineate the underlying mechanism. Transcriptome profiling showed that the Traf2- and Nck-interacting kinase (TNIK) gene was consistently upregulated in an array of SCLC PDXs exposed to chemoradiation compared with monotherapy, which is consistent with previous observations of TNIK amplification in human samples. Genetic depletion (P < 0.01) or pharmacologic inhibition (P < 0.0001) of TNIK reduced in vitro clonogenic survival of TNIKhigh SCLC cells and promoted sensitivity to chemoradiation. In vivo, pharmacologic inhibition of TNIK enhanced chemoradiation sensitivity (P < 0.0001) of the H446 cell line-derived xenograft (CDX) in NOD-SCID mice. Furthermore, pharmacologic inhibition of TNIK in vivo demonstrated sensitivity (P < 0.0001) to chemoradiotherapy (CRT) in LX33 PDX. These results indicate that TNIK plays a role in conferring resistance to chemoradiation in SCLC cell lines and in vivo in SCLC CDX and PDX models. Delineating the mechanism behind radiosensitization suggested that TNIK inhibition may impair the DNA damage response in irradiated cells. Collectively, these findings suggest that TNIK may be a promising therapeutic target in limited-stage SCLC and support further investigation of TNIK inhibition in combination with standard CRT.

Humans↗

PubMed2023

Dynamics and variability of transcriptomic dysregulation in congenital myotonic dystrophy during pediatric development.

Myotonic dystrophy type 1 (DM1) is a multi-systemic disorder caused by expansion of CTG microsatellite repeats within DMPK. The most severe form, congenital myotonic dystrophy (CDM), has symptom onset at birth due to large intergenerational repeat expansions. Despite a common mutation, CDM individuals present with a distinct clinical phenotype and absence of common DM1 symptoms. Given the clinical divergence, it is unknown if the hallmark of DM1 pathology, dysregulation of alternative splicing (AS) due to sequestration of MBNL proteins within toxic CUG repeat RNAs, contributes to disease throughout pediatric development. To evaluate global transcriptomic dysregulation, RNA-seq was performed on 36 CDM skeletal muscle biopsies ages 2 weeks to 16 years, including two longitudinal samples. Fifty DM1 and adult/pediatric controls were also sequenced as comparative groups. Despite a large CTG expansion and shared age of onset, CDM individuals presented with a heterogenous, MBNL-dependent mis-splicing signature. Estimation of intracellular MBNL concentrations from splicing responses of select events correlated with total spliceopathy and revealed a distinct, triphasic pattern of AS dysregulation across pediatric development. CDM infants (< 2 years) possess severe mis-splicing that significantly improves in early childhood (2-8 years) independent of sex or CTG repeat load. Adolescent individuals (8-16 years) stratified into two populations with a full range of global splicing dysregulation. DMPK expression changes correlated with alterations in splicing severity during development. This study reveals the complex dynamics of the CDM muscle transcriptome and provides insights into new therapeutic strategies, timing of therapeutic intervention, and biomarker development.

Child, Preschool↗

PubMed2026

Integrin α3 (ITGA3) expression across breast cancer subtypes: Prognosis and therapeutic relevance.

BACKGROUND: Integrin α3 (ITGA3), which heterodimerizes with integrin β1, has emerged as a potential biomarker and therapeutic target in several epithelial malignancies; however, its clinical relevance in breast cancer remains incompletely characterized. This study evaluated ITGA3 expression across breast cancer molecular subtypes and assessed its prognostic and predictive significance. METHODS: Immunohistochemistry (IHC) was performed on archival breast cancer specimens using tissue microarrays (n = 148) and whole-tissue sections (n = 21). Complete clinicopathologic and outcome data were available for 108 patients, including hormone receptor-positive/human epidermal growth factor receptor 2-negative, HER2-positive, and triple-negative breast cancer (TNBC) subtypes. ITGA3 expression was quantified using H-scores and correlated with clinicopathologic features and survival outcomes. Independent transcriptomic analyses were conducted using the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and the Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) cohorts to evaluate ITGA3 mRNA expression, co-expressed signaling pathways, and associations with therapeutic response. RESULTS: ITGA3 protein expression was detected in 85.2% of breast cancer specimens and was significantly higher in HR-positive/HER2-negative and HER2-positive tumors compared with TNBC (p < 0.0050). High ITGA3 expression was associated with shorter recurrence-free survival (p < 0.0001). In the METABRIC cohort, tumors with ITGA3 alterations demonstrated significantly worse relapse-free survival (p < 0.0001) and overall survival (p < 0.0500). Transcriptomic analyses revealed that ITGA3 co-expressed with estrogen receptor 1(ESR1), erb-b2 receptor tyrosine kinase 2 (ERBB2), and luminal markers, along with enrichment of estrogen receptor and phosphoinositide 3-kinase-protein kinase B-mechanistic target of rapamycin (PI3K/AKT/mTOR) signaling pathways. ITGA3 expression was not predictive of response to tamoxifen or trastuzumab. CONCLUSION: Elevated ITGA3 expression is associated with breast cancer recurrence and poor clinical outcomes, supporting its potential role as a prognostic biomarker and candidate therapeutic target.

Biomarkers↗

PubMed2026

Systematic discovery of retina-enriched Rik genes identifies 1190005I06Rik as a novel modulator of visual signalling.

BACKGROUND: High‑throughput transcriptome projects have revealed thousands of mammalian genes with little or no functional annotation. Among these are hundreds of loci assigned provisional “Rik” identifiers following discovery in the RIKEN cDNA annotation effort. Although often dismissed as genomic dark matter, such genes may encode tissue‑restricted proteins that modulate physiologic functions and influence disease. The retina is a highly specialised neural tissue and a common site of inherited disorders; understanding its molecular repertoire could illuminate novel therapeutic avenues. METHODS: We integrated bulk RNA‑seq from ten adult mouse tissues, evolutionary and domain analysis, single‑cell RNA‑seq, and CRISPR/Cas9 gene disruption to systematically catalogue protein‑coding Rik genes enriched in the retina and test the function of a representative gene. RESULTS: A rigorous differential expression analysis identified 44 Rik genes with robust retina‑specific expression compared with nine non‑retinal tissues. Many of these genes lack orthologues beyond rodents, while others show broad conservation, illustrating a continuum from lineage‑restricted to conserved retinopathy candidates. Single‑cell transcriptomics revealed that these genes are expressed across retinal cell types, with the highest aggregate expression in cone photoreceptors and inner interneurons. To evaluate physiological significance, we generated a 1190005I06Rik knockout mouse. Although retinal architecture appeared normal, loss of 1190005I06Rik enhanced electroretinogram b‑wave amplitudes and altered light‑avoidance behaviour, indicating that this previously uncharacterised gene acts as a negative modulator of visual signalling. CONCLUSIONS: We present a curated atlas of retina‑enriched Rik genes and demonstrate that 1190005I06RIK modulates retinal circuit function. This resource expands the molecular landscape of the retina and provides new candidates for the genetic basis of inherited retinal disease. Our findings underscore that unannotated genes may exert measurable effects on sensory processing and warrant systematic exploration in the context of human ocular disorders.

Animals↗

PubMed2024

Nonlethal deleterious mutation-induced stress accelerates bacterial aging.

Random mutagenesis, including when it leads to loss of gene function, is a key mechanism enabling microorganisms' long-term adaptation to new environments. However, loss-of-function mutations are often deleterious, triggering, in turn, cellular stress and complex homeostatic stress responses, called "allostasis," to promote cell survival. Here, we characterize the differential impacts of 65 nonlethal, deleterious single-gene deletions on Escherichia coli growth in three different growth environments. Further assessments of select mutants, namely, those bearing single adenosine triphosphate (ATP) synthase subunit deletions, reveal that mutants display reorganized transcriptome profiles that reflect both the environment and the specific gene deletion. We also find that ATP synthase α-subunit deleted (ΔatpA) cells exhibit elevated metabolic rates while having slower growth compared to wild-type (wt) E. coli cells. At the single-cell level, compared to wt cells, individual ΔatpA cells display near normal proliferation profiles but enter a postreplicative state earlier and exhibit a distinct senescence phenotype. These results highlight the complex interplay between genomic diversity, adaptation, and stress response and uncover an "aging cost" to individual bacterial cells for maintaining population-level resilience to environmental and genetic stress; they also suggest potential bacteriostatic antibiotic targets and -as select human genetic diseases display highly similar phenotypes, - a bacterial origin of some human diseases.

Escherichia coli↗

PubMed2026

Genome-guided stage- and tissue-resolved transcriptome analysis of Serrodes campana identifies sex-biased antennal expression and candidate chemosensory-related genes.

Serrodes campana is an erebid moth of ecological and forestry relevance; its larvae are mainly associated with the soapberry tree, Sapindus mukorossi, whereas adults exhibit fruit-piercing behavior. However, stage- and tissue-resolved transcriptomic resources for this species remain limited. Here, using a chromosome-level reference genome, we performed a genome-guided transcriptome analysis of S. campana based on 12 RNA-seq libraries representing major developmental stages and key adult tissues. Global transcriptomic analyses revealed pronounced transcriptional differentiation across developmental stages and tissue types. Tissue-enriched gene sets and functional enrichment analyses identified distinct molecular signatures associated with developmental, sensory, and pheromone-associated tissues. Comparative analysis of female and male antennae further revealed sex-biased expression of several candidate chemosensory-related genes. Among 153 curated chemosensory-related candidate genes, most odorant receptor genes showed strong antennal enrichment, whereas other major chemosensory gene families displayed broader but still tissue-preferential expression patterns. In addition, an exploratory comparison of female terminal abdominal gland tissue and male terminal abdominal coremata revealed divergent expression profiles and highlighted candidate genes potentially associated with pheromone-related physiology, reproduction, and tissue-specific signaling. Together, this study provides the first genome-guided stage- and tissue-resolved transcriptomic resource for S. campana and offers a useful foundation for future studies of chemosensory detection, sex-biased gene expression, and pheromone-associated biology in this species.

Animals↗