SEARCH · Search PubMed

Results for “RNA sequencing”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

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

At least 937 records · Page 52Linked to original sources

PubMed1984

Co-ordinate control of gene expression. Muscle-specific 7 S RNA contains sequences homologous to 3'-untranslated regions of myosin genes and repetitive DNA.

We have cloned and sequenced a complementary DNA copy (pSS48) of a novel muscle-specific, low molecular weight RNA, 7 S RNA, isolated from embryonic chick cardiac muscle cells. The hybridization pattern of plasmid pSS48 DNA to chick genomic DNA suggests that 7 S RNA is derived from the repetitive chick DNA with a repetition frequency of about 300 copies per haploid genome. Under low stringency, pSS48 DNA also hybridizes with high specificity to the single copy gene for chick myosin light chain (MLC) and to myosin heavy chain (MHC), and possibly to other co-ordinately expressed genes for chick muscle proteins. The sequence analysis of recombinant plasmids pSS48, pML10 and pMHC8, for 7 S RNA, MLC mRNA and MHC RNA, respectively, indicated that short nucleotide stretches homologous to 7 S RNA reside in the 3' untranslated regions of the respective genes. The 7 S RNA sequence appears to be highly specific for the chick muscle tissue, since RNA and DNA from several sources did not hybridize to pSS48 DNA. Furthermore, the 7 S RNA-like sequence(s) appears in chick blastodermal cells preferentially earlier than the onset of transcription of genes for major muscle proteins. These results, taken together, suggest a possible function for 7 S RNA in expression of muscle-specific genes during chick development.

Animals↗

PubMed1992

The complete nucleotide sequence of RNA 1 of a German isolate of barley yellow mosaic virus and its comparison with a Japanese isolate.

The nucleotide sequence of RNA 1 of a German isolate of barley yellow mosaic virus has been determined and compared with a Japanese isolate of the same virus. The sequence identity is 93.6% at the nucleotide level and 96% at the amino acid level. Similar values have been found for the polyproteins of the RNA 2 of both isolates (95%). Both isolates show an RNA 1-encoded protein arrangement similar to that of potyviruses such as tobacco etch virus. In contrast, the polyproteins of the small RNAs (RNA 2) do not show such a similarity to the polyproteins of other potyviruses. However, there is a striking difference between the two isolates in the generally highly conserved active site of the RNA-dependent RNA polymerase. The German isolate exactly matches the consensus sequences for previously described potyviral RNA-dependent RNA polymerases, whereas the Japanese isolate does not.

Amino Acid Sequence↗

PubMed2026

XXYLT1 and Mendelian Retinal Dystrophy.

IMPORTANCE: Substantial unexplained heritability remains for pathogenic inherited retinal disease (IRD) variants. Application of genome-wide association studies (GWAS) could help identify causal genes in rare diseases. OBJECTIVE: To leverage a GWAS for the discovery of IRD-associated genes. DESIGN, SETTING, AND PARTICIPANTS: This GWAS analysis was combined with replication of findings in 2 independent IRD cohorts. The study was conducted from January 2024 to December 2025 in a multicenter setting through FinnGen, 100 000 Genomes Project, and the National Health Service Genomic Medicine Service combined with clinical cohort from the Oulu University Hospital. Using IRD criteria from the International Classification of Diseases, 9th and 10th Revisions, 540 individuals with IRD and 473 945 control individuals were identified in the FinnGen study. For validation of FinnGen results, 49 patients were recruited from Oulu University Hospital. Results were further validated in 2 individuals identified from the UK cohort. MAIN OUTCOMES AND MEASURES: The GWAS and proteomics analysis were performed in the FinnGen cohort. Sanger and whole-genome sequencing and RNA approaches were used in a clinical IRD cohort to validate pathogenicity of the identified XXYLT1 variant. RESULTS: This GWAS identified 13 recessive loci reaching genome-wide significance (defined as P < 5 × 10-8). Of these, 4 (near or within XXYLT1, ANKRD10, DYM, and CBLN4) had not been associated with IRD, including the XXYLT1 c.505-1G>C founder variant. This variant was further genotyped in the clinical replication cohort, leading to identification of 5 more homozygous individuals from 4 families. The phenotype was consistent with a cone-rod or macular dystrophy, with visual deterioration, cystoid macular edema and/or schisislike macular abnormalities. The effect of the XXYLT1 c.505-1G>C variant was further investigated using RNA sequencing and complementary DNA amplicon sequencing, demonstrating exon 2 skipping and a loss-of-function effect. These findings were replicated in an independent population identifying 2 patients from the UK harboring a homozygous XXYLT1 c.766G>A, p.(Glu256Lys) missense variant. CONCLUSIONS AND RELEVANCE: This GWAS identified an association between XXYLT1 and IRD. These results affirm that GWAS in a founder population can be used as a potential tool for the discovery of rare mendelian disease genes and that XXYLT1 should be considered in clinical IRD gene panels.

Humans↗

PubMed2026

Dysregulation of U12-Type Splicing in Lupus Neutrophils.

OBJECTIVE: Neutrophil dysfunction is a hallmark of systemic lupus erythematosus (SLE), but its molecular basis remains unclear. This study explores transcriptional and posttranscriptional changes in low-density granulocytes (LDGs), a proinflammatory neutrophil subset expanded in SLE, focusing on NADPH oxidase (Nox) function and minor intron splicing. METHODS: LDGs and normal-density granulocytes (NDGs) were isolated from patients with SLE and healthy controls (HCs). CYBA (p22phox) expression was evaluated at transcript and protein levels. Nox activity was measured using luminol assays. Bulk RNA sequencing (RNA-seq) and rMATS software were used to assess alternative splicing, particularly of U12-type intron-containing genes. RESULTS: CYBA expression was reduced in SLE LDGs (n = 11) compared to SLE and HC NDGs (n = 6), with levels resembling those in chronic granulomatous disease neutrophils. SLE LDGs exhibited impaired Nox activity (n = 7 SLE, n = 12 HC). CYBA is a U12 intron-containing gene, and transcriptomic analysis revealed broad down-regulation of this gene class in SLE LDGs, suggesting minor spliceosome dysfunction. rMATS analysis showed increased U12-type intron retention and widespread splicing defects-including exon skipping and mutually exclusive exon use-in genes such as GBP5, MAEA, and STX10. These abnormalities were validated in an independent long-read RNA-seq data set from SLE peripheral blood mononuclear cells. Importantly, splicing disruptions correlated with disease activity and autoantibody profiles. CONCLUSION: Impaired U12-dependent splicing may contribute to neutrophil dysfunction in SLE, potentially via defective oxidative burst and altered immune regulation. These findings highlight the minor spliceosome as a novel player in lupus pathogenesis.

Humans↗

PubMed2026

A Multifaceted Interplay Among Hemophagocytosis, Interleukin-18, and Type I Interferon Distinguishes Still Disease From Other Autoinflammatory Diseases.

OBJECTIVE: The unknown pathophysiology and the lack of specific features for systemic juvenile idiopathic arthritis and adult-onset Still disease (collectively known as Still disease; SD) delay diagnosis and appropriate treatment. The goal of this study was to identify features and mechanisms that distinguish SD from other systemic autoinflammatory diseases (SAID). METHODS: Using the SomaScan assay and RNA sequencing (RNA-Seq), we determined the plasma proteomes and immune cell microRNA (miRNA) and RNA transcriptomes of 372 patients with SAID, respectively. Proteomic findings were validated by enzyme-linked immunosorbent assays. SD (n = 72) and non-SD SAIDs (n = 300) were compared to identify distinguishing features of SD. We performed integrated and unbiased analyses of all data sets using weighted gene correlation network analysis to identify feature modules that characterize SD and stratify patients. RESULTS: Elevated plasma heme oxygenase 1 (HO-1) and interleukin-18 (IL-18) strongly correlate and characterize SD but do not associate with general inflammation. SD was characterized by ferroptosis in plasma, type I interferon (IFN) signaling in monocyte transcriptomes, and elevated natural killer cell miRNA-146a-5p, which is an IL-18 induced miRNA. Finally, we identified feature modules that distinguish SD from other SAIDs and stratified patients with SD into two distinct subgroups not attributable to disease activity or inflammation but hemophagocytosis. CONCLUSION: This unprecedented large omics data set of SAIDs revealed that complex interactions among hemophagocytosis, IL-18, and type I IFN signaling characterize SD. Furthermore, two distinct subgroups in patients with SD were distinguished by the degree of hemophagocytic activity. Finally, the large proteomics and RNA-Seq data sets generated in this study can serve as an invaluable resource for the further investigation of SD and other SAIDs.

Humans↗

PubMed2026

Human Monocytic Models Reveal Genotype-Dependent Inflammatory Programs in VEXAS Syndrome.

OBJECTIVES: VEXAS syndrome is a severe X-linked autoinflammatory disorder caused by somatic mutations in ubiquitin-like modifier activating enzyme 1 (UBA1), with clinical outcomes that vary by UBA1 genotype. We aimed to elucidate genotype-specific inflammatory programs and identify potential therapeutic targets. METHODS: We conducted longitudinal deep phenotyping, including whole-blood RNA sequencing (RNA-seq) and clinical activity assessment. Peripheral blood samples were analyzed by single-cell RNA-seq. Human monocytic cell lines harboring each major UBA1 mutation (p.Met41Val, p.Met41Thr, or p.Met41Leu) were generated and subjected to transcriptomic and functional analyses. RESULTS: Thirteen patients with VEXAS syndrome contributed a total of 79 RNA-seq samples. Among genes upregulated in VEXAS syndrome, RNASE1 showed the strongest correlation with longitudinal disease activity (r = 0.70, FDR < 0.05) and was upregulated in patients' monocytes. In UBA1-mutant monocytic cell lines, genotype-dependent ubiquitination defects were observed in a graded manner (p.Met41Val > p.Met41Thr > p.Met41Leu), even in the absence of exogenous stimuli. These defects were accompanied by unfolded protein response activation, increased pro-inflammatory cytokine production, progressive cell death, and RNASE1 upregulation, all following the same graded pattern, recapitulating patient genotype-phenotype associations. Transcriptomic analyses demonstrated enrichment of pro-inflammatory, interferon, and necroptosis signatures in more severe genotypes. Notably, inhibition of receptor-interacting protein kinase 3 (RIPK3) markedly attenuated all pathological features, including RNASE1 upregulation. CONCLUSIONS: Our UBA1-mutant monocytic cell-line models, representing three distinct genotypes, recapitulate genotype-dependent inflammatory phenotypes that can be modulated by RIPK3 inhibition, providing a translational platform for mechanistic investigation and precision therapy development in VEXAS syndrome.

Journal Article↗

PubMed2026

Optical genome mapping enhanced by refined variant interpretation in pediatric acute lymphoblastic leukemia.

Reliable detection of structural variants (SVs) and copy number variations (CNVs) is crucial in the contemporary diagnostics of pediatric B-cell acute lymphoblastic leukemia (B-ALL). However, limitations of commonly used conventional and molecular cytogenetic methods may hinder the accurate genetic characterization of patients. Optical genome mapping (OGM) offers a reliable alternative by enabling high-resolution, genome-wide detection of CNVs and SVs. Chromosomal aberrations were screened using OGM in 51 children with B-ALL. The results were compared with those of karyotyping, fluorescence in situ hybridization (FISH), digital multiplex ligation-dependent probe amplification (digitalMLPA), and targeted RNA sequencing (RNA-seq). OGM data showed high congruency with karyotyping and FISH findings, detecting clinically relevant variants beyond G-banding results and unraveling a complex KMT2A fusion undetected by FISH. Gene fusions involved in complex ETV6::RUNX1 translocations, but not detected by RNA-seq, were confirmed using FISH. Normalization of OGM copy number values with DNA-index-improved concordance with FISH-derived copy numbers in near-tri/tetraploid cases. In the peripheral regions of OGM variants (fringe-zones), a novel evaluation strategy called 'FriZone' was applied, which significantly improved the concordance between OGM and digitalMLPA. In addition, a co-segregation analysis revealed strong associations between ETV6::RUNX1 fusion and deletions of ETV6, RAG2, and NR3C2. OGM uncovered complex rearrangements undetected by widely used methods in 15% of cases, improving genetic classification and risk stratification in 10% of the patients. The FriZone analysis and normalization by DNA-index provide a refined, more accurate approach to OGM variant interpretation, facilitating the efficient application of OGM in clinical diagnostics. © 2026 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Humans↗

PubMedDate not supplied

Taking variation of evolutionary rates between sites into account in inferring phylogenies.

As methods of molecular phylogeny have become more explicit and more biologically realistic following the pioneering work of Thomas Jukes, they have had to relax their initial assumption that rates of evolution were equal at all sites. Distance matrix and likelihood methods of inferring phylogenies make this assumption; parsimony, when valid, is less limited by it. Nucleotide sequences, including RNA sequences, can show substantial rate variation; protein sequences show rates that vary much more widely. Assuming a prior distribution of rates such as a gamma distribution or lognormal distribution has deservedly been popular, but for likelihood methods it leads to computational difficulties. These can be resolved using hidden Markov model (HMM) methods which approximate the distribution by one with a modest number of discrete rates. Generalized Laguerre quadrature can be used to improve the selection of rates and their probabilities so as to more nearly approach the desired gamma distribution. A model based on population genetics is presented predicting how the rates of evolution might vary from locus to locus. Challenges for the future include allowing rates at a given site to vary along the tree, as in the "covarion" model, and allowing them to have correlations that reflect three-dimensional structure, rather than position in the coding sequence. Markov chain Monte Carlo likelihood methods may be the only practical way to carry out computations for these models.

Algorithms↗

PubMed2026

Genome-wide AP2/ERF analysis identifies HmaERF87 as a positive regulator of Hydrangea macrophylla leaf spot resistance.

A total of 164 APETALA2/ethylene-responsive factor (AP2/ERF) genes were identified in Hydrangea macrophylla, and HmaERF87 positively contributes to leaf spot resistance. The APETALA2/ethylene-responsive factor (AP2/ERF) transcription factor family plays important roles in plant stress responses, but its contribution to disease resistance in Hydrangea macrophylla (hydrangea) remains poorly understood. In this study, 164 AP2/ERF genes were identified in the H. macrophylla genome and classified into APETALA2 (AP2), ethylene-responsive factor (ERF), dehydration-responsive element-binding (DREB), and related to ABI3/VP1 (RAV) subfamilies. Their chromosomal distribution, conserved motifs, gene structures, and duplication patterns were analyzed. A total of 46 pathogen-responsive H. macrophylla AP2/ERF (HmaERF) genes were identified from the RNA sequencing (RNA-seq) dataset of resistant and susceptible cultivar leaves collected before and after Corynespora cassiicola inoculation. Promoter analysis revealed that the HmaERF genes with upregulated expression post-C. cassiicola infection showed a higher frequency and copy number of jasmonate-responsive cis-regulatory elements, suggesting their possible involvement in hormone-mediated defense responses. Three infection-induced candidate genes, including HmaERF56, HmaERF87, and HmaERF129, were selected for functional validation using virus-induced gene silencing (VIGS) in hydrangea leaf discs. Silencing of HmaERF87 expression via VIGS significantly increased lesion development after C. cassiicola inoculation, whereas the transient overexpression of HmaERF87 reduced the area of leaf disc lesions. Subcellular localization showed that the HmaERF87 protein was localized in the nucleus, and yeast assays indicated that its transcriptional activation activity was mainly associated with the C-terminal region of the protein. These results support a role for HmaERF87 as a positive regulator of H. macrophylla resistance to leaf spot disease and provide a candidate gene for further studies of disease resistance in hydrangea.

Plant Proteins↗

PubMed2026

Association Between Ticagrelor and Glucose Homeostasis Regulation: Insights from Genetic and Transcriptomic Analyses.

Emerging evidence has demonstrated the additional therapeutic benefits of ticagrelor in acute coronary syndrome (ACS) patients with diabetes. However, the underlying mechanisms of this association remain elusive. Mendelian randomization (MR) analysis using genome-wide association study (GWAS) data on ticagrelor, plasma proteomics and type 2 diabetes was employed to identify causal mediator proteins. RNA sequencing (RNA-seq) of ticagrelor-treated HepG2 cells revealed the molecular pathways regulating glucose metabolism. Genetically proxied ticagrelor was significantly associated with a reduced risk of diabetes (OR = 0.859, 95% CI: 0.783-0.934, P = 7.98E-05), and 24.41% of this effect was mediated by upregulation of BDH2 protein. In vitro experiments confirmed the enhanced effect of ticagrelor on glucose consumption. Transcriptome analysis revealed that mitochondrial respiratory chain transfer and oxidative phosphorylation (OXPHOS) were significantly enriched, and genes related to ATP biosynthesis were significantly upregulated. These findings highlight the non-platelet function of ticagrelor in maintaining glucose homeostasis, providing insights into potential drug repurposing in the future.

Humans↗

PubMed2026

Bioinformatic analysis reveals the potential association of ESRP1 with the splicing of cytoskeleton-associated genes in doxorubicin-resistant MCF7 breast cancer cells.

BACKGROUND: Breast cancer remains one of the most prevalent malignancies among women, with doxorubicin resistance posing a significant challenge that undermines treatment success and survival outcomes. Aberrant alternative splicing (AS), driven by dysregulation or mutations in splicing factors (SFs), is implicated in cancer initiation, progression, and drug resistance. This study aims to investigate the association of the epithelial cell-specific splicing factor ESRP1 with doxorubicin resistance in breast cancer, focusing on how ESRP1 deficiency correlates with AS changes that promote chemoresistance. METHODS: We analyzed RNA-sequencing (RNA-seq) data from doxorubicin-resistant (MCF7-DR) and parental (MCF7) breast cancer cell lines to identify enhanced alternative splicing events (ASEs) and changes in ESRP1 expression; we further leveraged The Cancer Genome Atlas (TCGA)-BRCA cohort to construct an SF-RASE correlation network for screening core SFs (including ESRP1). An integrative analysis combining crosslinking immunoprecipitation (CLIP-seq) data and The Cancer Genome Atlas (TCGA) database was performed to validate ESRP1 binding targets and assess the association between ESRP1-related splicing and cytoskeleton organization. RESULTS: We observed extensive AS changes and significantly downregulated ESRP1 expression in MCF7-DR cells. Integrative analysis identified 61 high-confidence ASEs that correlate with ESRP1 expression. Further bioinformatic integration suggests that ESRP1 expression is associated with the splicing patterns of SPTBN1, MAP2K7, FGFR3, and CYB561A3-four genes involved in cytoskeleton organization-though direct experimental verification to confirm a causal regulatory relationship between ESRP1 and the splicing of these genes is still pending. CONCLUSIONS: Our findings suggest that ESRP1 expression is closely associated with doxorubicin resistance in breast cancer cells, with concomitant alterations in key ASEs linked to cytoskeletal remodeling that correlate with ESRP1. Exploring the ESRP1-related splicing network may offer new strategies to overcome chemoresistance and improve patient outcomes. However, the small cell line sample size (n = 2 per group) constrains the robustness of ASE and SF-ASE correlation findings, and these results should be interpreted with caution and require further validation with larger sample cohorts.

Alternative splicing↗

PubMed1990

The HIV-1 Tat protein: an RNA sequence-specific processivity factor?

Explore the source record for details and available documents.

Base Sequence↗

PubMed2026

RBFOX3 regulates hippocampal transcriptomic programs to maintain synaptic and ultrastructural integrity.

RBFOX3 is a neuron-specific RNA-binding protein essential for maintaining brain circuit homeostasis and functional connectivity. Genetic disruptions in RBFOX3 are clinically linked to cognitive impairment, epilepsy, and sleep disorders. Although global Rbfox3 knockout (Rbfox3-/-) mouse models have established its necessity in hippocampus-dependent neuronal circuits and behaviors, the underlying hippocampal transcriptomic landscape and synaptic ultrastructure remain poorly understood. To address these gaps, we integrated hippocampal RNA-sequencing from Rbfox3-/- mice with high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation analysis. We identified 3,401 differentially expressed genes in the hippocampus of Rbfox3-/- mice, confirming 1,920 as candidate RBFOX3 targets. Gene Ontology enrichment analysis revealed that these candidate targets converge on pathways governing neuronal morphogenesis, synaptic transmission, dendritic development, and cognition. Furthermore, transmission electron microscopy of the hippocampal dentate gyrus revealed that while the overall presynaptic area remained unaltered, Rbfox3 deletion reduced presynaptic vesicle number, presynaptic mitochondria area, and postsynaptic density thickness. Collectively, our findings demonstrate that RBFOX3 acts as a critical regulator orchestrating the transcriptomic programs required for hippocampal structural and functional maturation, revealing that its loss compromises both the metabolic and structural architecture of the synapse.

Hippocampus↗

PubMed2026

Transcriptomic responses of gill and intestinal tissues in Nile tilapia (Oreochromis niloticus) to bacterial infection following sequential nanoimmersion and hydrogel-based multivalent vaccination.

Bacterial pathogens, including Flavobacterium oreochromis, Aeromonas veronii, Streptococcus agalactiae, and Edwardsiella tarda, represent major infectious threats to Nile tilapia (Oreochromis niloticus). A multivalent vaccination strategy integrating cationic nanoemulsion immersion with oral hydrogel boosters was developed to investigate tissue-specific immune responses at the transcriptomic level. Gill tissues were collected following immersion challenge and intestinal tissues following intraperitoneal injection challenge, reflecting the physiologically relevant infection biology of each pathogen and the mechanistic rationale of each delivery platform. RNA sequencing (RNA-seq) generated high-quality datasets (mapping rate > 81.64%) with strong concordance to quantitative real-time PCR (qRT-PCR) validation (r = 0.83). Comparative transcriptomic analysis revealed distinct yet complementary immune signatures between tissues. Gill transcriptomes were enriched in phagosome, focal adhesion, extracellular matrix-receptor interaction (ECM-receptor interaction), and cytokine-cytokine receptor interaction pathways, accompanied by increased expression of major histocompatibility complex class I/II (MHC class I/II), mannose receptor, αVβ3 integrin, and calnexin, indicating innate activation, enhanced phagocytic capacity, epithelial barrier reinforcement, and adaptive immune coordination. Intestinal transcriptomes showed predominant enrichment of adaptive immune pathways, including the intestinal immune network for immunoglobulin (Ig) production, Forkhead box O (FoxO) signaling, and mitogen-activated protein kinase (MAPK) signaling, with increased expression of T-cell receptor (TCR), inducible T-cell co-stimulator ligand (ICOS-L), C-X-C chemokine receptor type 4 (CXCR4), and polymeric immunoglobulin receptor (pIgR), reflecting T and B cell coordination, lymphocyte trafficking, and mucosal immunoglobulin transport, alongside innate engagement through phagosome pathway enrichment. Shared upregulation of MHC class II, B-cell receptor (BCR) signaling, integrin alpha M (ITGAM), and immunoglobulin-associated components across both tissues suggests coordinated mucosal immune activation through a conserved immune module, warranting direct experimental validation. Collectively, these findings provide transcriptomic evidence that this vaccination strategy elicits an integrated, tissue-specialized immune response, advancing mechanistic understanding of gill and intestinal immunity in vaccine-induced protection of teleost fish.

Animals↗

PubMed2025

Genetic and chromatin regulation of Pvt1 monoallelic expression.

While most genes are equivalently expressed on both alleles, genes with random monoallelic expression (RME) stably maintain expression from only one allele, but the mechanisms and consequences of RME remain unclear. We performed allele-specific RNA sequencing (RNA-seq) on ∼100 F1 hybrid neural progenitor cell (NPC) clonal lines to reveal the extent of autosomal RME (aRME). Of the 287 aRME genes, Pvt1, an oncogenic long non-coding RNA, is an aRME with a genetic bias. In the absence of genetic differences, Pvt1 undergoes balanced aRME. Pvt1 monoallelic expression is maintained by allele-specific active and repressive histone modifications, opposed to DNA methylation. Additionally, we provide a two-step mechanism for the initiation of aRME and demonstrate that Pvt1 monoallelic expression results in a growth phenotype due to the interplay with Myc. These findings provide insight into how genetic differences can skew a stochastic process, resulting in monoallelic expression with a phenotypic consequence in early development.

Chromatin↗

PubMed2026

Plasma proteins are integral to cross-tissue gene regulatory networks implicated in cardiometabolic disorders and coronary artery disease.

The plasma proteome has demonstrated promise for identifying diagnostic markers for cardiometabolic disorders (CMDs) and coronary artery disease (CAD). However, identifying the organ of origin for these biomarkers is critical for establishing biological relevance. We performed a multi-omic integrative analysis across multiple tissues from the STARNET study by profiling 974 plasma proteins in 532 CAD patients, integrating RNA sequencing (RNA-seq) data from the arterial wall, major metabolic organs, and blood. We identified 144 cis-protein quantitative trait loci in plasma, colocalizing with tissue cis-expression quantitative trait loci. Additionally, by mapping tissue mRNA "seed genes," we traced 262 plasma proteins to their source organs, primarily the liver. Crucially, we found that 851 plasma proteins are associated with the activity of cross-tissue gene regulatory networks (GRNs), including GRNs implicated in CMD and CAD development. Our findings demonstrate that plasma proteins are integral components of GRNs, with potential for developing reliable diagnostics and precise therapeutic targets. A record of this paper's transparent peer review process is included in the supplemental information.

cardiometabolic disorders↗

PubMed2026

RNU4ATAC-opathy: Clinical, molecular, and transcriptomic insights from a large cohort.

PURPOSE: We aim to better define the genotype and phenotype spectrum of RNU4ATAC-opathy, demonstrate the utility of RNA sequencing (RNA-seq) for variant classification, and highlight the challenges in detecting variants in this noncoding gene. METHODS: Sixty individuals with molecularly confirmed RNU4ATAC-opathy were recruited from multiple clinical and research centers internationally. RNA-seq was available for 7 affected individuals. RESULTS: We report the clinical and molecular findings of 60 individuals, including 42 not previously described, and 33 distinct RNU4ATAC variants, 13 of which are novel. Core features in this cohort-present in most individuals assessed and varying in severity-include microcephaly, short stature, skeletal anomalies, developmental delay, cerebral anomalies, skin conditions, and immune deficiency. Additional findings, such as diabetes, holoprosencephaly, and the absence of various core features in some individuals, highlight the broad phenotypic spectrum. All individuals who underwent RNA-seq showed a consistent pattern of minor intron retention. In 6 individuals, RNA-seq enabled the reclassification of variants of uncertain significance as likely pathogenic. Although RNU4ATAC variants are generally covered by clinical exomes, they are often overlooked in analysis because of their noncoding nature. CONCLUSION: This study highlights the variability of phenotypes and genotypes associated with RNU4ATAC-opathy. Laboratories should ensure RNU4ATAC and other noncoding genes are appropriately assessed by their analysis pipelines.

Lowry-Wood syndrome↗

PubMed2024

RNA editing in host lncRNAs as potential modulator in SARS-CoV-2 variants-host immune response dynamics.

Both host and viral RNA editing plays a crucial role in host's response to infection, yet our understanding of host RNA editing remains limited. In this study of in-house generated RNA sequencing (RNA-seq) data of 211 hospitalized COVID-19 patients with PreVOC, Delta, and Omicron variants, we observed a significant differential editing frequency and patterns in long non-coding RNAs (lncRNAs), with Delta group displaying lower RNA editing compared to PreVOC/Omicron patients. Notably, multiple transcripts of UGDH-AS1 and NEAT1 exhibited high editing frequencies. Expression of ADAR1/APOBEC3A/APOBEC3G and differential abundance of repeats were possible modulators of differential editing across patient groups. We observed a shift in crucial infection-related pathways wherein the pathways were downregulated in Delta compared to PreVOC and Omicron. Our genomics-based evidence suggests that lncRNA editing influences stability, miRNA binding, and expression of both lncRNA and target genes. Overall, the study highlights the role of lncRNAs and how editing within host lncRNAs modulates the disease severity.

Biological sciences↗