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PubMed2026

COVID-19 multi-omics reveal organ-specific responses and biomarkers.

OBJECTIVE: Post-COVID-19 syndrome is characterised by persistent immune dysfunction and multi-organ sequelae. This study aimed to characterise the systemic blood molecular landscape induced by SARS-CoV-2 infection and identify prognostic markers linked to skeletal muscle mass loss, a key driver of poor outcomes. METHODS: We enrolled 30 healthy controls and 307 COVID-19 patients, collecting 422 plasma samples for integrated proteomic and metabolomic profiling to investigate organ-specific molecular alterations in COVID-19. RESULTS: We comprehensively mapped the molecular landscape of COVID-19, encompassing immune, tissue-specific, and metabolic perturbations, and delineated their interactions. Focusing on organ-damage-related molecular patterns associated with disease progression and mortality, we found that skeletal muscle mass loss contributed to poor clinical outcomes of COVID-19 (p < 0.0001). Dysregulated arginine metabolism emerged as a key metabolic signature in fatal COVID-19 cases, with GLUL, GOT1, and citrulline showing significant correlation with skeletal muscle mass loss. Longitudinal analyses further revealed that reduced citrulline levels underlie the poor outcome of COVID-19 patients with muscle mass loss. These findings were robustly supported through multiple approaches: Mendelian randomization confirmed causal relationships between citrulline depletion, sarcopenia/fat-free mass loss, and COVID-19 mortality (p < 0.05), transcriptomic analyses of SARS-CoV-2-infected golden hamsters (GSE231910) provided additional support in enrichment of arginine biosynthesis (FDR < 0.05), and in vitro experiments further demonstrated that citrulline depletion promotes pro-inflammatory M1 macrophage polarisation — a key immunological feature of critical COVID-19. Leveraging these insights, we developed a skeletal muscle loss-specific prognostic prediction model for COVID-19 using GLUL, GOT1, and citrulline. This model effectively stratified patients into high- and low-risk groups (p = 0.035). CONCLUSION: Our study advances the understanding of COVID-19-induced organ pathophysiology and provides a foundation for developing targeted therapeutic strategies for post-COVID sequelae.

COVID-19↗

PubMed2026

Integrative evidence-knowledge marker selection enhances LLM-based cell type annotation in single-cell RNA-seq analysis.

BACKGROUND: Cell type annotation is essential for gaining biological insight from single-cell RNA sequencing data, yet manual labeling remains time-consuming and difficult to reproduce. Various computational approaches have been developed to automate this process, and recent studies suggest that large language models can infer cell types with promising accuracy in single-cell analysis. However, most workflows still rely on cluster-specific markers derived from gene expression alone or manual curation. As a result, marker selection can be sensitive to statistical criteria and dataset-dependent bias, which may lead to the selection of less informative genes or missing important markers, while providing limited biological context. RESULTS: To address this limitation, we introduce CELLIA, an LLM-based workflow for automated and robust cell type annotation. CELLIA employs an integrative evidence-knowledge marker selection strategy that combines statistical differential expression criteria with curated tissue-specific marker resources to identify informative marker genes. In benchmarking analyses of 102 cell types, this approach improved agreement with manual annotations. In addition, CELLIA achieved higher agreement in subtype-level analyses of closely related immune populations and was further evaluated in a non-immune stromal subtype setting, covering 25 cell types in total. CONCLUSION: By integrating evidence-knowledge from gene expression with curated biological prior knowledge, CELLIA provides a more stable marker selection and improves the reliability of LLM-cell type annotation.

Cell type annotation↗

PubMed2022

CMTr mediated 2'-O-ribose methylation status of cap-adjacent nucleotides across animals.

Cap methyltransferases (CMTrs) O methylate the 2' position of the ribose (cOMe) of cap-adjacent nucleotides of animal, protist, and viral mRNAs. Animals generally have two CMTrs, whereas trypanosomes have three, and many viruses encode one in their genome. In the splice leader of mRNAs in trypanosomes, the first four nucleotides contain cOMe, but little is known about the status of cOMe in animals. Here, we show that cOMe is prominently present on the first two cap-adjacent nucleotides with species- and tissue-specific variations in Caenorhabditis elegans, honeybees, zebrafish, mouse, and human cell lines. In contrast, Drosophila contains cOMe primarily on the first cap-adjacent nucleotide. De novo RoseTTA modeling of CMTrs reveals close similarities of the overall structure and near identity for the catalytic tetrad, and for cap and cofactor binding for human, Drosophila and C. elegans CMTrs. Although viral CMTrs maintain the overall structure and catalytic tetrad, they have diverged in cap and cofactor binding. Consistent with the structural similarity, both CMTrs from Drosophila and humans methylate the first cap-adjacent nucleotide of an AGU consensus start. Because the second nucleotide is also methylated upon heat stress in Drosophila, these findings argue for regulated cOMe important for gene expression regulation.

Animals↗

PubMed2025

Gut fungi are associated with human genetic variation and disease risk.

Human genetic determinants of the gut mycobiome remain uninvestigated despite decades of research highlighting tripartite relationships between gut bacteria, genetic background, and disease. Here, we present the first genome-wide association study on the number and types of human genetic loci influencing gut fungi relative abundance. We detect 148 fungi-associated variants (FAVs) across 7 chromosomes that statistically associate with 9 fungal taxa. Of these FAVs, several occur in the protein-coding genes PTPRC, ANAPC10, NAV2, and CDH13. Additional FAVs link to tissue-specific gene expression as fungi-associated expression quantitative trait loci. Notably, the relative abundance of gut yeast Kazachstania associates with genetic variation in CDH13 encoding T-cadherin, a protein linked to cardiovascular disease. Kazachstania forms a causal relationship with cardiovascular disease risk in a mendelian two-sample randomization analysis. These findings establish previously unrecognized connections between human genetics, gut fungi, and chronic disease, broadening the paradigm of human-microbe interactions in the gut to the mycobiome.

Humans↗

PubMed2026

IBAS: Interaction-bridged association studies discovering novel genes underlying complex traits.

Genetic contributions to complex traits are often mediated through coordinated gene-gene interaction networks, yet most existing association frameworks focus on marginal single-gene effects and overlook higher-order dependency structures. Direct modeling of interactions remains challenging due to combinatorial complexity and statistical instability. We introduce Interaction-Bridged Association Study (IBAS), a general framework that incorporates pathway-level interaction patterns into genotype-phenotype association analysis without explicitly enumerating interactions. IBAS leverages transcriptomic reference data to construct low-dimensional representations of pathway activity, which guide SNP-weighting and gene-level association testing within a kernel-based framework. In perturbation-based simulations, IBAS demonstrates improved stability and reproducibility compared to conventional TWAS and gene-based methods, while maintaining well-calibrated Type I error under phenotype permutation. Application to the WTCCC datasets identifies both known and novel genes across multiple complex diseases, including candidates with modest marginal effects missed by standard approaches. These findings are supported by replication in an independent cohort, and analyses across multiple reference tissues revealing both shared and tissue-specific signals. Overall, IBAS provides a statistically robust and computationally tractable framework for incorporating interaction effects into association mapping, extending beyond the single-gene paradigm and enabling more comprehensive characterization of complex trait. IBAS is available on GitHub at: https://github.com/QingrunZhangLab/IBAS.

Polymorphism, Single Nucleotide↗

PubMed2024

Expression pattern of Stlhcb gene family in potato and effects of overexpression of Stcp24 gene on potato photosynthesis.

Potato is one of the four staple food crops in the world. It has a wide range of cultivation, high yield, and high nutritional value. Enhancing the photosynthesis of potato is particularly important as it leads to an increase in the potato yield. The light-harvesting pigment-binding protein complex is very important for plant photosynthesis. We identified 12 Stlhcb gene family members from the potato variety "Atlantic" using transcriptome sequencing and bioinformatics. The proteins encoded by the Stlhcb gene family have between 3358 and 4852 atomic number, a relative molecular weight between 24060.16 and 34624.54 Da, and an isoelectric point between 4.99 and 8.65. The RT-qPCR results showed that the 12 Stlhcb genes were expressed in a tissue-specific and time-dependent fashion under low light. The relative expression of the Stlhcb genes in the leaves was significantly higher than that in the stems and roots, and the relative expression of these genes first increased and then decreased with the prolongation of light exposure time. The Stcp24 gene with the highest expression was cloned, and an expression vector was constructed. A subcellular localization analysis was performed in tobacco and an overexpression experiment was performed in potato using an Agrobacterium-mediated method. The subcellular localization analysis showed that the protein encoded by Stcp24 was located in chloroplasts as expected. Overexpression of Stcp24 in transgenic potato increased the yield of potatoes and the content of chlorophyll a and b; increased the net photosynthetic rate, transpiration rate, stomatal conductance, electron transport efficiency, and semi-saturated light intensity; and promoted photosynthesis and plant growth. This study provides a reference for the study of the function of the potato light-harvesting pigment-binding protein gene family. It lays a foundation for further study of the mechanism of the photosynthesis of potato, improvement of the light energy utilization of potato, and molecular breeding of potato.

Solanum tuberosum↗

PubMed2026

From gut to pancreas: Shared genetic susceptibility and biological convergence in acute pancreatitis and Crohn's disease.

BACKGROUND: Acute pancreatitis (AP) and Crohn's disease (CD) exhibit overlapping clinical presentations and an unexpectedly high rate of comorbidity. Whether this reflects shared genetic susceptibilities remains unclear. METHODS: We performed a cross-trait genome-wide association analysis leveraging European-ancestry summary statistics for AP (Ncases = 8446; Ncontrols = 437,418) and CD (Ncases = 12,194; Ncontrols = 28,072). Firstly, cross-trait genetic correlation was estimated using linkage disequilibrium score regression (LDSC) and high-definition likelihood (HDL). Secondly, to pinpoint specific pleiotropic loci and prioritize candidate genes, we employed PLACO under a rigorous composite null hypothesis, integrated with Bayesian colocalization and SMR/HEIDI analyses. Finally, we dissected the underlying biological context by mapping tissue-specific regulatory enrichment and pathway convergence using FUMA, MAGMA, and Stratified LD Score Regression (S-LDSC). RESULTS: AP and CD showed significant positive genetic correlation (LDSC: rg = 0.178, SE = 0.079, P = 0.025; HDL: rg = 0.294, SE = 0.096, P = 0.0021). Pleiotropy analyses revealed 86 SNPs and 6 independent genome-wide significant pleiotropic loci (lead variants at 5q33.1, 6q22.33, 7q34, 10q24.2, 15q22.33 and 19q13.11, PPLACO < 5 × 10-8). Colocalization showed suggestive evidence of a shared causal signal at 6q22.33 (PP4 = 0.666). Gene-based tests of the AP-CD cross-trait statistics prioritized eight pleiotropic genes-RSPO3, ATG16L1, SMAD3, FADS1, ZPBP2, FADS2, PRKAA1 and IRGM. Gene-set analyses highlighted IL-23/Th17-related and broader inflammatory response pathways. CONCLUSIONS: AP and CD share polygenic susceptibility and converge on immune and inflammatory processes, with prioritized genes pointing to autophagy, lipid metabolism and TGF-β/SMAD-related biology.

Humans↗

PubMed2026

The Potential Link Between Eosinophilic Esophagitis and Food Allergy: Inflammatory Pathogenesis and Management.

Eosinophilic esophagitis (EoE) has transitioned from an isolated gastrointestinal disorder to a recognized type 2 immune-mediated allergic disease, most likely representing a late manifestation of the atopic march. This comprehensive review examines the complex inflammatory pathogenesis linking EoE and food allergy, and critically discusses the mechanisms of disease induction, dietary treatments, and emerging clinical challenges. While genome-wide association studies identify shared susceptibility loci with classic atopy, EoE exhibits distinct tissue-specific pathways, particularly dominated by the local interleukin (IL)-13 axis and highly esophagus-selective proteases like Calpain-14. This unique immunological interplay is clinically epitomized by food oral immunotherapy (OIT)-induced EoE. During OIT, systemic immune reprogramming successfully drives immune tolerance-marked by a robust increase in plasma food-specific IgG4-but fails at the local level, due to the persistence of pathogenic Th2 cells and aberrant mucosal IgG4 immune complex deposition within the esophageal lamina propria. Regarding therapeutic management, conventional skin and serum allergy testing remain highly inaccurate in identifying dietary triggers, rendering test-guided diets ineffective. Conversely, empiric elimination diets achieve robust histological remission, ranging from standardized six-food restrictions to pragmatic single-food approaches targeting cow's milk. Furthermore, novel insights into industrial milk processing (such as UHT sterilization and homogenization) and specific beta-casein genetic variants (A1 vs A2) highlight how altered protein structures generate neoantigens that accelerate esophageal immunogenicity. In conclusion, decoding the divergent immunological mechanisms operating in the refractory esophagus is essential to move beyond trial-and-error dietary interventions towards non-invasive monitoring tools, precision medicine, and optimized biological therapies in EoE management.

Calpain14↗

PubMed2026

A horizontally acquired gene mediates insect cocoon pigmentation in the eri silkmoth, Samia ricini.

Holometabolous insects make cocoons during larval-pupal metamorphosis to protect the pupal phase. The materials used for cocoon construction vary widely. Lepidopteran insects typically secrete silk to form cocoons, which display diverse colors. The eri silkworm, Samia cynthia ricini, is an economically important domesticated species that mostly produces white cocoons, with some varieties producing red cocoons. The enzyme kynureninase (KYNU), acquired from bacteria by horizontal gene transfer, has previously been implicated in insect coloration, while the tryptophan metabolite 3-hydroxyanthranilic acid (3-HAA) has been identified as a red pigment. However, exactly how KYNU is involved in cocoon pigmentation remains unclear. Here, we report that a horizontally transferred bacterial gene encoding KYNU regulates red cocoon formation. Metabolomic analysis revealed a high accumulation of 3-HAA in red cocoons, confirming its role as the primary pigment and associating the coloration with tryptophan metabolism. Quantitative real-time polymerase chain reaction (qPCR) analysis indicated that SrKYNU is highly expressed in the silk glands and significantly downregulated in the red cocoon strain compared to the white cocoon strain. Genomic sequencing identified a 141 bp deletion in the upstream regulatory region of KYNU in the red cocoon strain compared to the white cocoon strain. Dual-luciferase assays confirmed that this deletion significantly reduced promoter activity. CRISPR/Cas9 knockout of SrKYNU in the white-cocoon strain resulted in mutants producing red cocoons with elevated 3-HAA content. These findings reveal that the horizontally transferred gene SrKYNU exhibits tissue-specific expression and regulates cocoon coloration in S. ricini, illustrating that horizontal gene transfer can play an important role in regulating an insect physiological process.

Animals↗

PubMed2026

Genomic insights into local adaptation of indigenous chickens.

Indigenous chickens are an essential part of biodiversity and a vital protein resource to humans, yet global warming and environmental changes pose serious threats to their survival and productivity. Therefore, assessing population adaptive capacity under shifting environments is crucial for breeding resilient animals, and guiding conservation strategies. Here, we integrated ecological and whole-genome resequencing data from 1 022 chickens from 44 Chinese indigenous populations to reveal genomic signatures of local adaptation. From 87 agroclimatic variables, we identified eight dominant environmental factors including solar radiation, precipitation, diurnal temperature range, and five landcover variables (cropland areas, water areas, trees coverage, bare ground and shrubs coverage) that shape ecological niches of indigenous chickens. Landscape and comparative genomics analyses revealed both known and novel candidate genes, such as UNC80, PTPRO, NCOR2, CSF2RB, NXT2 and PALLD for the solar radiation, precipitation, diurnal temperature range, cropland areas, trees coverage and bare ground, respectively. Particularly, adaptive non-coding variants harbored in these genes exhibited spatial allelic changes across populations and acted as regulatory elements via chromatin accessibility and DNA methylation, influencing adaptation in a tissue-specific manner. Our findings underscore the rich genetic diversity of Chinese indigenous chickens and provide new insights into genomic mechanisms of local adaptation, offering valuable references for domestic animal breeding, conservation, and climate resilience.

Animals↗

PubMed2026

Genome-wide identification of the superoxide dismutase gene family in Lycium barbarum and their expression profiles under abiotic stress and phytohormone treatment.

BACKGROUND: Superoxide dismutases (SODs) are crucial metalloenzymes that constitute the first line of defense against reactive oxygen species in plants under abiotic stress. Wolfberry (Lycium barbarum) is an economically important medicinal plant with notable stress tolerance, however, a comprehensive genome-wide analysis of its SOD gene family has not yet been performed. RESULTS: We identified ten wolfberry SOD genes (LbaSODs) and classified them into three subfamilies: iron-SODs (Fe-SODs), manganese-SODs (Mn-SODs), and copper/zinc-SODs (Cu/Zn-SODs). Members within each subfamily shared conserved gene structures and motifs. Segmental duplication was the primary driver of LbaSOD expansion, with three paralogous pairs identified. Analysis of cis-regulatory elements in the promoter region revealed a predominance of stress- and hormone-responsive cis-elements, particularly ABA-responsive elements (ABREs) (22 copies) and LTR (17 copies) motifs. Tissue-specific expression profiling revealed that LbaSOD2 and LbaSOD5 expression peaked during early fruit development, whereas LbaSOD6, LbaSOD9, and LbaSOD10 were progressively upregulated through fruit maturation. Under abiotic conditions, Fe-SOD members were markedly suppressed during prolonged drought, whereas LbaSOD9 and LbaSOD10 were rapidly induced in response to salt stress. Among the phytohormone treatments, methyl jasmonate (MeJA) elicited the most pronounced response, with LbaSOD5 expression increasing by approximately 60-fold after 24 hours. Notably, abscisic acid (ABA) triggered an exceptionally strong transcriptional induction of LbaSOD5 (2.5 × 105-fold), LbaSOD10 (6 × 105-fold), and LbaSOD6 (70-fold). In addition, LbaSOD3 and LbaSOD7 transcripts were undetectable in any of the tested conditions. CONCLUSIONS: This study provides the first comprehensive characterization of the LbaSOD gene family and elucidates its hormone- and stress-responsive regulatory landscape, providing a valuable foundation for future functional investigations of LbaSOD genes in abiotic stress adaptation. The extraordinarily strong ABA-mediated induction of specific LbaSOD members, together with their tissue- and stress-specific expression patterns, highlights their potential as targets for genetic improvement of stress tolerance in wolfberry.

Lycium barbarum↗

PubMed2026

Systematic mining and characterization of metal transporter families regulating zinc homeostasis provide insights into metal homeostasis in Camellia sinensis.

BACKGROUND AND AIMS: Zinc is essential for tea plant growth and quality formation, yet its homeostatic mechanisms remain poorly understood. This study identified metal transporter families regulating zinc homeostasis, analyzed their evolution, structure, and expression, and clarified zinc uptake, transport, detoxification networks, and their links to metabolism. METHODS: This study identified zinc homeostasis-related metal transporter families in the tea plant genome, characterized their structural features and expression profiles across tissues and developmental stages through integrative bioinformatics and transcriptomic analyses, and delineated the molecular mechanisms underlying zinc uptake, translocation, and detoxification by systematically integrating published evidence. RESULTS: This study identified 74 metal transporter genes from six families: 13 CsZIPs, 12 CsNRAMPs, 10 CsHMAs, 10 CsYSLs, 14 CsMTPs, and 15 CsCAXs in the 'Shuchazao2' genome, revealing closer affinity to woody species than to Arabidopsis. These proteins exhibit conserved domains, diverse subcellular localizations (cell membrane, vacuole, chloroplast, and Golgi apparatus), and tissue-specific expression with abundant stress/hormone-responsive cis-elements. At the plant-soil interface, tea plants mobilize rhizospheric zinc via proton and organic acid secretion; CsYSLs, CsNRAMPs, and CsZIPs mediate zinc uptake, aided by arbuscular mycorrhizal fungi (AMF) and plant growth-promoting rhizobacteria (PGPR) that expand root absorption zones. Xylem CsHMAs and phloem CsYSLs coordinate root-to-shoot zinc translocation, and vacuolar transporters (CsMTPs, CsCAXs), cell wall immobilization, and antioxidant systems alleviate high-zinc stress injury. CONCLUSIONS: These findings collectively delineate an integrated zinc "acquisition-distribution-buffering" network in tea plants, offering a repertoire of candidate genes with potential utility in zinc biofortification breeding and improving acid soil adaptation. Further experimental validation, including tea transgenesis, zinc-stress qRT-PCR, and heterologous functional complementation, is essential to substantiate their biological roles.

Camellia sinensis↗

PubMed2026

Cucurbitacins in Plant-Insect Interactions: Biosynthesis, Regulation, Ecological Functions, and Prospects for Crop Protection.

Cucurbitacins are highly oxygenated tetracyclic triterpenoids characterized by intense bitterness, substantial structural diversity, and important consequences for plant-herbivore interactions. Although best known from Cucurbitaceae, cucurbitacins and related cucurbitane-type metabolites also occur in phylogenetically distant herbaceous and woody plants. Genetic and biochemical studies have validated several core biosynthetic steps, including cucurbitadienol formation by oxidosqualene cyclases and subsequent modification by cytochrome P450 monooxygenases, acyltransferases, and glycosyltransferases. Tissue-preferential basic helix-loop-helix transcription factors constitute the best-characterized regulatory layer, whereas the evidence supporting accessory regulators, transporters, and environmental responses varies from functional validation to transcriptomic or genomic prediction. From the plant perspective, cucurbitacins deter feeding or impair performance in many generalist and non-adapted herbivores. By contrast, their use as host-recognition cues and feeding stimulants by specialist diabroticite beetles reflects evolved herbivore adaptations involving perception, tolerance, metabolism, or sequestration rather than a second defensive function of the plant trait. Herbivore-induced cucurbitacin accumulation has been demonstrated in particular systems, although its regulatory mechanisms and ecological generality remain unresolved. Unlike previous reviews centered primarily on cucurbitacin chemistry, pharmacological activity, or individual biosynthetic pathways, this review integrates evidence-graded pathway reconstruction and molecular regulation with taxonomic distribution, insect adaptation, domestication, and agroecological consequences. Mechanistically, this review traces how scaffold formation, oxidative tailoring, conjugation, tissue-specific regulation, and transport give rise to contrasting ecological outcomes through herbivore-specific perception, tolerance, metabolism, and sequestration. We conclude that uniformly increasing or eliminating cucurbitacins is unlikely to provide broadly effective crop resistance because either direction may favor a different herbivore group. Future priorities include functional validation of candidate genes, spatially resolved metabolite analysis, comparative investigation of non-cucurbit lineages, and field evaluation involving generalist and specialist herbivores, crop quality, and non-target organisms. These advances will support context-specific fruit-quality improvement, behavioral pest control, and integrated pest management strategies rather than cucurbitacin manipulation as a stand-alone resistance approach.

agroecology↗

PubMed2026

Genome-Wide Identification of the Soybean GH5 Gene Family and Functional Analysis of GmGH5-22 in Salt Tolerance.

Plant GH5 family genes function in both cell wall biosynthesis and stress responses. However, comprehensive studies on GH5 genes in the soybean remain limited. Here, we identified 28 GmGH5 genes from the soybean genome. Phylogenetic analysis assigned these genes to three subfamilies (I-III), with no representatives in subfamily IV. The GmGH5 family harbors 15 conserved motifs, which are largely similar within subfamilies but differ across subfamilies. Additionally, exon-intron structures (2-7 introns) exhibit clade-specific patterns, with members within the same clade sharing similar intron numbers and lengths, whereas distinct clades show some variation. The promoter regions of GmGH5 genes contained various cis-acting regulatory elements associated with stress responses and developmental processes. Transcriptome-based expression profiling revealed distinct tissue-specific expression patterns of GmGH5 genes. RT-qPCR further confirmed their differential expression under salt, alkaline, cold, and drought stresses, especially a significant increase in GmGH5-22 expression under salt stress (approximately 22-fold at 6 h, **** p < 0.0001). Furthermore, GmGH5-22 was highly expressed in roots, and transient expression in tobacco leaves showed its peripheral localization, which aligns with its predicted extracellular localization, suggesting that GmGH5-22 is highly likely localized to the cell wall. Overexpression of GmGH5-22 in soybean hairy roots significantly improved tolerance to salt stress. These findings establish a foundation for functional characterization of GmGH5 genes and provide viable targets for molecular breeding to enhance salt tolerance in soybeans.

GH5 family↗

PubMed2026

The Key Trichoderma-Induced Gene Encoding a DUF568 Domain-Containing Protein Mediates Defense Responses in Wheat.

Genes encoding DUF568 domain-containing proteins participate in plant stress adaptation. To elucidate the functional role of DUF568 domain-containing genes in Trichoderma-induced wheat defense responses against wheat Fusarium crown rot, we performed a genome-wide identification and characterization of the TaDUF568 gene family in hexaploid wheat (Triticum aestivum L.). In this study, a total of 33 TaDUF568 family genes were systematically identified and characterized at the genome-wide level, exhibiting uneven chromosomal distribution and diverse physicochemical properties. Phylogenetic, structural, and collinearity analyses revealed conserved family characteristics among monocot species. Segmental duplication was verified as the primary driver of gene family expansion. Expression profiling revealed divergent tissue-specific expression patterns among TaDUF568 family members, among which TaDUF568.18 was strongly induced by Trichoderma M2. Subcellular localization assays confirmed that TaDUF568.18 is a plasma membrane-localized protein. Functional validation via stable transgenes demonstrated that overexpression of TaDUF568.18 restricted lesion expansion, improved agronomic traits, and enhanced disease resistance. This study is the first to characterize the wheat DUF568 family and confirm that TaDUF568.18 (annotated as TaAIR12) acts as a positive regulator of Trichoderma-mediated wheat defense, providing a valuable gene resource for wheat disease-resistance breeding.

DUF568↗

PubMed2026

Clinical Variant Interpretation with the Integrative Genomics Viewer (IGV) for Molecular Pathologists.

The integrative genomics viewer (IGV) is a pivotal tool in clinical genomics, enabling the visualization and interpretation of complex sequencing data. Bringing clinical knowledge to bear with visual evaluation of sequencing results is the primary means by which molecular pathologists and other professionals assess and finalize cases. A variety of software tools can assist, but their relationship to the underlying data must be understood and applied systematically. This study includes essential background on next-generation sequencing (NGS) data file types (e.g., FASTQ, BAM, VCF) with a discussion of their format and purpose. We then describe features of IGV that derive nuances from these files. We utilize a series of curated practical cases based on clinical vignettes through which the reader will interact with clinical NGS sequencing data using the IGV software to review various types of clinically relevant variants relative to the human reference genome. These clinical vignettes have been curated to describe examples of some of the complexities of interpretation of genomic data, and how utilizing IGV as part of a routine workflow can provide additional interpretive information for variants beyond routine bioinformatic software algorithm variant calls. The visual inspection of genomic variants utilizing the tools within IGV can unmask subtle contextual cues (i.e., variant allele frequency, strand bias, tissue-specific context) that can influence the interpretation of genomic variants. Although this study focuses on using IGV for the detection and interpretation of somatic variants, the provided applications can be extrapolated for use in the germline setting, including analysis of complex variants and detection of mosaicism.

Humans↗

PubMed2026

Genetic evidence prioritizes circulating proteins for heart failure beyond shared BMI-related genetic liability.

BACKGROUND: Heart failure (HF) and body mass index (BMI) share substantial genetic architecture, which may lead genetically informed target discovery to preferentially identify adiposity-related pathways. We sought to identify circulating proteins associated with HF beyond this shared genetic component. METHODS: We applied GWAS-by-subtraction to overall HF, nonischemic HF, and nonischemic HF with reduced or preserved ejection fraction to derive BMI-related and BMI-subtracted HF components. We then performed proteome-wide cis-pQTL Mendelian randomization and colocalization using four independent proteomic cohorts, followed by tissue-specific eQTL colocalization, cardiac transcriptomic annotation, and druggability assessment. RESULTS: Compared with the original HF phenotypes, the BMI-subtracted components showed attenuated genetic correlations with BMI (0.045-0.147) while retaining 28 independent loci for overall HF and nine for nonischemic HF. Across 19,930 protein-HF tests, 11 associations involving nine proteins were prioritized by the Mendelian randomization and colocalization analyses. For example, a 1-SD increase in genetically predicted CELSR2 abundance was associated with lower overall HF risk (odds ratio, 0.96 [95% CI, 0.94-0.98]; P=8.6×10-7), whereas a 1-SD increase in genetically predicted CSF3 abundance was associated with higher nonischemic HF risk (odds ratio, 1.32 [95% CI, 1.18-1.48]; P=2.0×10-6). CELSR2 and TMEM106B colocalized with cis-eQTLs in failing left ventricular myocardium, and DAG1 showed cardiomyocyte enrichment with concordant downregulation in failing hearts. CONCLUSIONS: We identified nine circulating proteins associated with HF beyond the genetic component shared with BMI. These findings extend the range of genetically supported pathways implicated in HF and nominate candidate proteins for further mechanistic and therapeutic investigation.

Genetics↗

PubMed2026

TNF-NF-κB signaling mediates immune-biomineralization crosstalk during shell repair under ocean acidification in Mytilus edulis.

Ocean acidification (OA) impairs biomineralization in bivalves, but its effects on immune-biomineralization crosstalk during shell repair remain unknown. Here, we exposed adult Mytilus edulis bearing standardized shell perforations to three pH levels (8.1, 7.9, and 7.7) for up to 40 days. OA slowed early repair and caused microstructural disorganization and an approximately 87% reduction of compressive strength at pH 7.7, yet the damaged area appeared largely closed by day 15, suggesting a decoupling between morphological closure and functional recovery. In addition, transcriptomic profiling of hemocytes and mantle tissue, based on an average of 6.5 Gb of clean reads per sample mapped to the M. edulis reference genome (NCBI Assembly GCF_000511035.1), revealed that these shell-level defects were accompanied by coordinated immune and metabolic reprogramming. Hemocytes, the primary immune effector cells of bivalves, exhibited pH- and time-dependent shifts with moderate acidification (pH 7.9) promoting inflammatory transcripts, whereas severe acidification (pH 7.7) suppressed these signals while upregulating stress-associated pathways; both treatments consistently downregulated lysosomal proteases and NF-κB negative regulators. The mantle, a primarily mineralizing organ, paradoxically upregulated immune-related genes while suppressing oxidative phosphorylation and extracellular matrix pathways. This tissue-level imbalance, with hemocytes recruited but functionally constrained and mantle metabolically suppressed yet immunologically activated, points to TNF-NF-κB pathway modulation as a key mediator of shell repair under acidification. Our findings demonstrate that visible shell closure masks underlying structural and mechanical failure, and that immune regulation, rather than simple suppression or activation, critically shapes the repair outcome. These results advocate for multifunctional indicators beyond closure area to assess shell integrity in acidified marine environments.

Animals↗