Biology subjects

Sun, Z.

Publications and source records attributed to Sun, Z..

At least 19 recordsLinked to original sources

bioRxiv2026

PETRO enables robust estimation of on-target perturbation effects in Perturb-seq

Perturb-seq uses multiple guides per target as replicates, but off-target effects can bias target-level estimates even with efficient target perturbation. We present PETRO, which recovers the on-target perturbation effect while allowing, for each outcome, an unknown minority of guides to have arbitrary off-target effects. Across CRISPRa and CRISPRi datasets, sequence-associated off-target bias persisted after pooling cells across guides and nearly doubled in one CRISPRa dataset after a published guide filter. PETRO largely removed this bias and reduced transmission of effects from independently flagged promiscuous guides. In simulations, PETRO nearly matched pooling in power without off-target effects; with off-target effects, pooling remained biased as cell numbers increased, whereas PETRO recovered the on-target perturbation effect. In cortical Perturb-seq, most ZNF219 pathway enrichments from pooling rested on one guide and did not survive majority-supported aggregation, unlike those for targets with concordant guides. PETRO enables robust target-level Perturb-seq analysis from replicate-guide agreement.

genomics↗

bioRxiv2026

EnsPlex: Integrative Protein Complex Prediction through Multi-source Complementary Structural Sampling and Topology-Aware Candidate Selection

Protein complex structure prediction depends on both the breadth of candidate coverage and the ability to select accurate models within a limited output budget. Most existing approaches emphasize only one stage. End-to-end models and molecular docking workflows generate candidate structures, whereas quality-assessment models primarily rerank a predefined candidate pool. A complete strategy must account for complementary sampling across generators, differences among scoring scales and the allocation of final candidate quotas. Here, EnsPlex is presented as a multi-source framework that couples structural sampling with candidate selection for protein-protein interaction complex prediction. EnsPlex combines conformation-expanded docking, AlphaFold-Multimer, AlphaFold3 and Boltz-1 to expand the sampled conformational space. Conformation-expanded docking comprises monomer conformational expansion followed by flexible HADDOCK docking. FACET is trained to predict candidate quality using DockQ and its component metrics as supervision. Across 102 antigen-antibody systems, EnsPlex achieved up to a 27.8% relative improvement in target success rate over AlphaFold3 with its built-in ranking under matched output budgets. FACET also improved within-source ranking in the internal candidate pools and in homology-filtered external data. These findings support the utility of EnsPlex for structure prediction in the evaluated antigen-antibody systems.

bioinformatics↗

bioRxiv2026

Multi-omic profiling reveals impaired luteal resolution and CHK2-regulated inflammation in ovarian aging

The ovary ages earlier than most other organs, but the molecular mechanisms that drive this decline remain unclear. To gain more insight into this process, we profiled ovaries from young and reproductively aged mice after synchronized ovulation and found that aging was marked by the accumulation of luteal cells with increased steroidogenic, antigen presentation and inflammatory gene expression. DNA methylation was globally preserved in aged ovaries but showed focal age-associated changes at gene regulatory regions. Protein profiling identified an increase in checkpoint kinase 2 (CHK2), a DNA damage response protein encoded by the CHEK2 gene associated with the timing of natural menopause in humans. CHK2 and DNA damage markers were increased in aged mice and human ovarian somatic cells. Transient CHK2 inhibition in aged mice increased the proportion of mature oocytes and blastocyst formation and reversed inflammatory signatures in granulosa cells. These findings identify defective luteal resolution and inflammation as features of ovarian aging and suggest that CHK2 induces a reversible age-associated inflammatory signature. Our results show that reproductive decline may remain pharmacologically modifiable during ovarian aging via regulation of the inflammatory response.

molecular biology↗

bioRxiv2026

Senescence-associated KRAS upregulation in peripheral T cells links to premature coronary artery disease

Aims: Premature coronary artery disease (PCAD) lacks specific molecular drivers, and the role of immunosenescence is unclear. We investigated whether aging-related gene dysregulation in T cells contributes to PCAD. Methods: We combined bulk transcriptomics of PBMCs from 12 PCAD patients and 21 controls, single-cell RNA sequencing of PBMCs and human atherosclerotic plaques, weighted gene co-expression network analysis, gene perturbation network analysis, and molecular docking. Results: KRAS was identified as a hub gene intersecting PCAD-associated genes and aging-related genes. Single-cell analysis showed KRAS upregulation predominantly in effector CD8+ T cells, which exhibited the highest senescence scores that were further elevated in disease. Network perturbation of KRAS strongly impacted the cell killing pathway. KRAS-high effector CD8+ T cells were detected in coronary and carotid plaques, displaying enhanced cytotoxicity, exhaustion, and senescence features. Additionally, a candidate small molecule was computationally predicted to bind inactive KRAS. Conclusions: Elevated KRAS expression in senescent, cytotoxic CD8+ T cells is associated with PCAD, bridging immunosenescence and premature atherosclerosis. This finding provides a novel biomarker candidate and potential therapeutic entry point, awaiting further functional validation.

bioinformatics↗

bioRxiv2026

GPR182 promotes atherosclerosis via facilitating arterial lipid deposition

Elevated circulating low-density lipoprotein cholesterol (LDL-C) is a primary risk factor for atherosclerosis; however, the molecular mechanisms underlying lipid plaque formation within the artery wall remain poorly understood. Here, we identify GPR182, a recently characterized lipoprotein receptor of the atypical chemokine receptor family, as a key mediator of lipid deposition in the aortic endothelium during atherosclerosis. Genetic depletion of GPR182 protects against atherosclerosis across multiple mouse models without altering circulating cholesterol levels or immune cell recruitment to plaques. GPR182 is expressed by aortic endothelial cells (ECs) and is further upregulated during disease progression. GPR182 mediates LDL uptake by aortic ECs both in vitro and in vivo. Blockade of GPR182 with a monoclonal antibody reduces lipid uptake in the aorta and attenuates disease progression under hypercholesterolemic conditions. Collectively, these findings identify endothelial GPR182 as a critical regulator of aortic lipid deposition and atherosclerotic plaque formation and support GPR182 inhibition as a promising therapy for atherosclerotic cardiovascular disease.

molecular biology↗

bioRxiv2026

Mitochondrial protein import couples proteostasis failure to mitochondrial permeabilization

Proteostasis failure is a hallmark of stress and disease, yet how it compromises mitochondrial integrity remains unclear. Here, we identify mitochondrial protein import as a critical pathway linking proteostasis failure to mitochondrial injury. We show that Raptinal, previously characterized as a rapid inducer of apoptosis, impairs the folding of newly synthesized proteins rather than directly disrupting mitochondrial membranes. The resulting proteotoxic stress drives mitochondrial outer membrane permeabilization and intrinsic apoptosis independently of BCL-2 family pore-forming proteins. VBIT4, a compound commonly used to maintain mitochondrial integrity, inhibited this pathway, and chemical proteomics with a photoaffinity analogue implicated the TIM23 import machinery. Genetic or pharmacological inhibition of the TIM23-PAM axis suppressed mitochondrial permeabilization without affecting canonical BAX-BAK-dependent apoptosis. These findings establish that mitochondrial protein import couples translation-associated proteotoxic stress to mitochondrial injury and identify regulation of import flux as a determinant of mitochondrial integrity during proteostasis failure.

cell biology↗

bioRxiv2026

Normative modelling of cortical networks identifies subtypes of type 2 diabetes associated with distinct clinical and transcriptomic profiles

Type 2 diabetes (T2D) is characterized by substantial clinical heterogeneity, yet its neurobiological substrates remain unclear. Here, we leverage normative modelling of cortical morphometric networks to quantify individual-level brain deviations using structural MRI data from 3,723 participants (1,941 T2D patients and 1,782 healthy controls) across three independent cohorts. Data-driven clustering reveals two robust T2D biotypes characterized by widespread positive (biotype 1) and negative (biotype 2) brain deviations. Despite comparable overall metabolic burdens, these biotypes feature distinct brain-metabolic coupling patterns: biotype 1 is primarily associated with lipid metabolism, whereas biotype 2 reflects a multifactorial metabolic burden spanning glycaemic control, adiposity, lipid, vascular risks, and disease duration. These divergent brain vulnerability profiles have distinct cognitive consequences; notably, biotype 2 shows poorer performance in complex cognitive tasks, aligning with negatively deviated connectivity gradients along the sensorimotor-to-association axis. Spatial transcriptomic analyses further link biotype 2 deviations to gene expression patterns enriched in insulin signalling, mitochondrial functions, tight junctions, and neurodegenerative disease pathways, alongside specific involvement of inhibitory neurons and oligodendrocyte lineage cells. Our findings provide a neurobiological understanding of T2D heterogeneity and establish a data-driven framework for characterizing personalized brain vulnerability, with implications for advancing precision diabetes medicine.

neuroscience↗

bioRxiv2026

Real-time near-infrared imaging distinguishes nasopharyngeal colonization from aspiration of Streptococcus pneumoniae and identifies aspiration as a trigger of severe disease

Streptococcus pneumoniae asymptomatically colonizes the nasopharynx but can invade the lower respiratory tract to cause life-threatening disease, particularly in older adults. However, whether the initial site of bacterial deposition following intranasal inoculation determines disease progression has not been directly examined. Here, we developed a near-infrared (NIR) fluorescence imaging approach using indocyanine green (ICG)-labeled S. pneumoniae TIGR4 to visualize early bacterial distribution in real time. ICG labeling by simple mixing, without genetic or chemical modification, neither impaired bacterial growth at 33 or 37{degrees}C, nor altered acid tolerance. Continuous video imaging during the first 10 min of infection resolved two distinct patterns: bacteria confined to the nasopharynx (colonization) and those aspirated into the lower respiratory tract (aspiration). Kaplan-Meier analysis revealed markedly higher mortality in the aspiration group in both young (hazard ratio = 7.9) and aged (hazard ratio = 8.4) mice, despite a 10-fold lower inoculum used for aged animals, with deaths beginning on day 3. Systemic profiling of blood at 24 h by RNA sequencing and plasma proteomics revealed that early aspiration in aged mice was associated with the activation of inflammatory and hematopoietic programs, enrichment of complement and coagulation cascades, and phagocytic pathways. Together, these findings establish aspiration into the lower respiratory tract as a trigger of severe pneumococcal disease and introduce real-time NIR imaging as a technique for linking early infection dynamics to systemic host responses.

microbiology↗

bioRxiv2026

Blocking primer improves detection of tick-borne pathogens in Ixodes scapularis (black-legged ticks) from a Lyme disease hotspot region in eastern Ontario, Canada.

Tick-borne pathogen (TBP) surveillance strategies that rely exclusively on targeted methods like PCR (PCR) or immunoblots do not benefit from strain-level sequence variation. Bacterial 16S rRNA metabarcoding offers more agnostic detection but is constrained in I. scapularis by the dominance of a maternally inherited endosymbiont, Rickettsia buchneri. Here we report the design and evaluation of three R. buchneri-specific blocking primers to suppress endosymbiont amplification during full-length 16S rRNA library preparation. Of these, primer 18F-Rb-C3 reduced R. buchneri relative abundance approximately 32-fold. We applied 18F-Rb-C3 with V4-16S metabarcode sequencing on 67 ticks collected from farm animals in Eastern Ontario and compared Borrelia species detection against qPCR. The V4-16S rRNA metabarcoding identified Borrelia species in 21 samples, whereas qPCR detected Borrelia in 24 samples and 11 samples were detected by both methods. Additionally, metabarcoding detected Anaplasma phagocytophilum in 12 samples, including seven samples coinfected with Borrelia, in the same assay. Variation relevant to strain surveillance was also detected by sequencing, though V4-16S was not sufficient to resolve closely related Borrelia genospecies or A. phagocytophilum variants. These findings demonstrate that blocking primer 18F-Rb-C3 enhances sensitivity of amplicon sequencing to the level of qPCR while also detecting other pathogens and sequence variants in a single assay.

genomics↗

bioRxiv2026

Endothelial ANGPT2 insufficiency impairs retinal vascularization with ROP-like neovascular tufts

ANGPT2 is widely recognized as a critical regulator of pathological neovascularization. By analyzing scRNA-seq data from neonatal retinas, we demonstrate that Angpt2 transcripts are highly enriched in tip cells relative to other endothelial subtypes, where Angpt1/4 expression is absent. However, mechanisms underlying ANGPT2 function at angiogenic fronts remain inadequately understood. Here, we show that endothelial Angpt2 deletion severely disrupted retinal vascularization, characterized by neovascular tufts and micro-hemorrhage. Similar angiogenic defects also occurred in the brain, but were less evident in other tissues examined. Mechanistically, ANGPT2 insufficiency attenuated retinal tip cell invasion with aberrant mural cell coverage, compromising sprouting into non-vascularized tissues. Retinal RNA-seq analysis revealed that transcripts associated with endothelial migration and junction assembly were reduced in Angpt2 mutants compared to littermate controls, while upregulated genes were enriched in hypoxia-responsive pathways and mural cell development. Notably, abnormal mural-tip cell associations were detected within 48 hours post-Angpt2 deletion, displaying also a hypoxia-driven transcriptomic signature. These closely resemble the vascular pathologies observed in human retinopathy of prematurity. In contrast, Angpt1 insufficiency or Angpt4 deficiency primarily affected venous morphogenesis. Collectively, our findings imply that ANGPT2 is essential for driving tip cell invasion during sprouting angiogenesis, and that its insufficiency triggers hypoxia-driven vascular anomalies.

developmental biology↗

bioRxiv2026

Psychotic-like experiences in children born very preterm: evidence from clinical and population-based cohorts

Background and aimVery preterm birth (VPT; [≤]32 weeks gestation) is associated with an increased risk of later psychiatric disorders, including psychosis. Although psychosis typically emerges in adulthood, subclinical early signs along the psychosis continuum, such as psychotic-like experiences (PLEs), can be observed much earlier. We therefore aimed to study PLEs in childhood in VPT individuals recruited from a clinical cohort compared with full-term (FT) controls. We subsequently investigated whether findings could be replicated in an independent population-based cohort. MethodsPrimary analyses were conducted in the Brain, Immunity and Psychopathology (BIPP) study, including 197 children born VPT recruited through Neonatal Intensive Care Units and 72 FT controls assessed at a mean age of 10.50{+/-}1.77 years. Between-group differences in PLEs were then examined in the Adolescent Brain Cognitive Development (ABCD) study, including 149 children born VPT and 9519 FT controls assessed at a mean age of 9.94 {+/-} 0.63 years. PLEs were assessed using the Prodromal Questionnaire-Brief Child Version (PQ-BC), yielding frequency and distress-related scores for both the total scale and three specific domains (unusual thought content, perceptual abnormalities, disorganised speech). Regression models tested associations between birth status (VPT and control) and PQ-BC scores adjusting for age, sex, and socio-economic status, with secondary models additionally adjusting for cognitive ability and broader psychopathology. Pooled analyses examined cohort effects (BIPP and ABCD) and cohort-by-group status (VPT and control) interactions. ResultsIn BIPP, VPT birth was associated with higher PQ-BC total ({beta}=1.61, p=0.004) and distress scores ({beta}=0.78, p=0.039), with the strongest and most consistent associations observed for perceptual abnormalities across total score (sum of endorsed items), distressing items, and distress severity scores (all p[≤]0.01). These associations were attenuated but largely persisted after adjustment for cognitive ability and broader psychopathology, particularly for perceptual abnormalities. In ABCD, VPT birth was not significantly associated with global or domain-specific PQ-BC outcomes. DiscussionVPT birth is associated with increased vulnerability to PLEs in childhood, particularly in the domain of perceptual abnormalities. The lack of clear replication in the population-based ABCD cohort may reflect differences in the composition of its VPT subgroup, which may not fully represent VPT individuals typically seen in clinical cohorts.

developmental biology↗

bioRxiv2026

Inhibition of Pseudomonas aeruginosa-secreted protease IV reduces lung

The opportunistic pathogen Pseudomonas aeruginosa secretes numerous proteases that disrupt host defenses. Among them, the lysyl endopeptidase PrpL has been implicated in virulence, but its role in inflammatory responses has remained unclear. This study shows that purified PrpL activates the AP-1 transcription factors following instillation into mouse lungs, and drives robust production of IL-1{beta}, IL-6, and TNF, as well as clinical symptoms. A proteolytically inactive mutant of PrpL fails to elicit these responses. Structural analysis of the complex of PrpL and its natural inhibitory propeptide (PrpLPP) using X-ray crystallography revealed the inhibitory mechanism of PrpLPP, which guided the identification of a pre-existing dipeptide inhibitor (LasBi) that blocked PrpL activity and restricted AP-1-driven cytokine induction and clinical symptoms in vivo. This study shows that the alkaline protease AprA degrades PrpLPP and functions redundantly with LasB to liberate mature, active PrpL. Our findings: 1) establish PrpL as a key virulence factor that triggers AP-1-mediated inflammatory signaling, 2) provide structural and functional insights into PrpL inhibition, and 3) identify AprA as a novel upstream PrpL activator. Together, these results highlight PrpL as a promising anti-virulence therapeutic target. Given the functional redundancy of inflammatory effectors produced by P. aeruginosa, strategies aimed at mitigating P. aeruginosa-induced lung inflammation through PrpL inhibition would likely need to be combined with approaches targeting additional pro-inflammatory bacterial factors. Author SummaryWe identify PrpL as a critical Pseudomonas aeruginosa protease that activates the inflammatory transcription factor AP-1 and drives potent lung inflammation. Structural analysis of a natural PrpL inhibitor guided development of an existing dipeptide inhibitor that significantly reduced the production of proinflammatory cytokines and clinical responses in vivo. Moreover, discovery of the AprA protease as an additional PrpL activator refines the activation model and suggests potential upstream therapeutic strategies. These findings highlight PrpL as both a driver of pathogenesis and a promising therapeutic target for treating P. aeruginosa infections.

microbiology↗

bioRxiv2026

Structural bioinformatics of three Epstein-Barr Virus (EBV) Integral Membrane Proteins and their water-soluble QTY analogs

The Epstein-Barr virus (EBV) is a highly prevalent virus worldwide that is associated with several lymphoid and epithelial malignancies. However, extensive research on EBV integral membrane proteins BILF1, LMP1 and LMP2, has been scarce due to their hydrophobic transmembrane domains. Our study applies the QTY code (glutamine, threonine, tyrosine) to design water-soluble analogs of BILF1, LMP1 and LMP2 with reduced hydrophobicity, where we systematically replaced hydrophobic amino acid residues leucine (L), isoleucine (I), valine (V), and phenylalanine (F) with structurally similar polar residues glutamine (Q), threonine (T), and tyrosine (Y). We retrieved their native sequences from UniProt, identified transmembrane domains using Protter, then performed QTY design through the Protein Solubilizing Server (PSS). We then predicted native and QTY structures using in silico prediction tools AlphaFold3, ColabFold, and Boltz-2. Our analyses demonstrate that despite significant protein sequence replacements in their transmembrane domains (54.15%-61.59%) and increased intrinsic solubility, the QTY analogs exhibited minimal changes in isoelectric point (0.00-0.15 decrease) and molecular weight (0.7-1.2 kDa increase). Additionally, structural superpositions between QTY analogs and native structures using PyMOL yield low RMSD values (0.217[A] -1.202[A]). Our results demonstrate the QTY codes ability to design detergent-free analogs of BILF1, LMP1 and LMP2 with substantially reduced hydrophobicity and aggregation propensity whilst preserving native-like structures. Our results may facilitate protein characterization studies, therapeutic research on EBV, and other protocols that typically require protein solubilization.

bioinformatics↗

bioRxiv2026

Oral Gut Microbial Axis in Inflammatory Bowel Disease and Primary Sclerosing Cholangitis

The oral cavity is increasingly recognized as a reservoir of microbes that can translocate to and influence the gut microbiome. This oral-gut microbial axis may contribute to the pathogenesis of chronic gastrointestinal and hepatobiliary disorders, including inflammatory bowel disease (IBD) and its comorbidity, primary sclerosing cholangitis (PSC). To investigate the oral-gut microbial axis in IBD and PSC, we enrolled 191 participants spanning Crohns disease (CD), ulcerative colitis (UC), CD with PSC (CD-PSC), UC with PSC (UC-PSC), and healthy controls. We generated and analyzed the whole-metagenome shotgun sequencing data from saliva, tongue swabs, and fecal samples. Across oral and gut niches, we identified multiple microbial species differentially enriched in participants with UC compared with healthy controls, including Fusobacterium nucleatum and Gemella sanguinis in saliva, Catonella massiliensis and Tannerella serpentiformis on the tongue, and G. sanguinis and Sellimonas intestinalis in feces. Paired oral-gut analyses revealed 15 potential oral-origin species enriched in fecal samples; notably, G. sanguinis and Veillonella rogosae were consistently enriched in participants with UC. These findings were further supported by an external validation dataset comprising 1,716 gut metagenomes from five independent IBD cohorts, highlighting the reproducibility of oral microbial signatures. In exploratory analyses, smoking history was associated with shifts in the oral microbiome toward a UC-like state in healthy controls, suggesting a possible environmental modifier of the oral-gut microbial axis. Collectively, our study identifies distinct oral microbial signatures and their potential translocation to the gut in IBD and PSC, underscoring the role of the oral- gut microbial axis in disease progression.

microbiology↗

bioRxiv2026

A High-Confidence Atlas of Protein Methylation Enables AI-Driven Detection of Methylated Peptides

Lysine and arginine methylation regulate chromatin dynamics, transcription, and cellular signaling, however confident mass spectrometry (MS)-based detection and localization of this modification remain challenging. We reanalyzed eight public human methylation-enriched datasets using an open and standardized workflow that integrates database searching via the Trans-Proteomic Pipeline with a decoy-based statistical method for the independent estimation of false localization rates (FLR). This yielded a high-confidence Human Methylation Atlas of 1,828 sites (57 methyl-lysine, 1,771 methyl-arginine) across 1,021 proteins, classified into Gold, Silver, and Bronze confidence tiers. This is far fewer sites than reported in previous studies, reflecting the application of stringent FLR control, and what we hypothesise is potential high-false discovery in previous analyses. We then leveraged this resource to adapt a deep learning-based methodology for the improved detection of methylated peptides. Three mouse methylation-enriched datasets were reanalysed to augment training, and the phosphoproteomics-trained AHLF (ad hoc learning of peptide fragmentation) model was fine-tuned by transfer learning to create AHLF-Methylation. The model achieved mean ROC-AUC values of 0.824 on human spectra, and 0.829 on combined human-mouse spectra. The atlas is available through PTMeXchange and PRIDE, with curated site evidence integrated into UniProt and PeptideAtlas.

bioinformatics↗

bioRxiv2026

Germline regulation of tumor evolutionary dynamics shapes multiple myeloma progression

Germline variation shapes cancer risk, yet its influence on the evolutionary dynamics of established tumors remains poorly understood. In multiple myeloma, subclonal diversification drives disease progression and treatment failure, but the heritable factors that modulate this process are unknown. Here, we show that germline variation is associated with tumor evolutionary features, implicating inherited regulation in subclonal expansion. Integrating germline variation with tumor evolutionary parameters identifies variants associated with evolutionary features, with signals enriched in regulatory regions, consistent with a transcriptional basis. We further identify TBKBP1 as a key locus linking germline variation to tumor evolution and clinical outcome. Germline variation at this locus is associated with TBKBP1 expression and subclonal expansion, and TBKBP1 expression correlates with adverse prognosis, consistent across independent cohorts. Functional analyses demonstrate that TBKBP1 promotes proliferation and activates MYC, mTORC1 and non-canonical NF-{kappa}B signaling pathway. Together, these findings establish germline regulatory variation as a determinant of tumor evolutionary dynamics and identify TBKBP1 as a mediator linking inherited variation to subclonal expansion and disease progression in multiple myeloma.

bioinformatics↗

bioRxiv2026

Genome Assembly of the Green Revolution Wheat Cultivar Pavon 76 Establishes a Reference for CIMMYT-Derived Wheat

Common wheat (Triticum aestivum L.) is a cornerstone of global food security. However, the standard reference genome, IWGSC RefSeq v2.1, is derived from wheat cultivar Chinese Spring, a historically important lineage that is not representative of modern cultivated wheat. In contrast, Pavon 76 is a CIMMYT Green Revolution wheat cultivar grown worldwide and is present in the pedigrees of numerous elite wheats, as well as in the genetic background of over 600 cytogenetic stocks used in studies ranging from recombination to male sterility. As no Pavon 76 reference has been reported, interpretation of these Pavon 76-derived stocks has relied on the genetically distant IWGSC RefSeq v2.1. To address this gap, we generated PacBio HiFi reads and Hi-C read pairs to assemble Pavon 76s genome. The final assembly comprises the expected 21 chromosomes, spans 15 Gb, and has an N50 of 710 Mb. Annotation identified 167,201 genes, of which 89.5% were functionally annotated. Comparative sequence and gene synteny analysis between Pavon 76 and IWGSC RefSeq v2.1 revealed significant structural divergence, establishing that IWGSC RefSeq v2.1 is not fully representative of modern wheats. This robust Pavon 76 assembly establishes the first chromosome-scale de novo assembly of a CIMMYT-derived wheat and provides a foundation for future genetic and genomic studies.

genomics↗

bioRxiv2026

Trichome acylsugar defenses are equally effective against leaf-mining and free-living insects

Trichomes are epidermal projections, crucial components of plant defense systems. Whether these epidermal defenses are effective against leafminers, which infest the internal mesophyll layers, remains unclear. Using the devasting invasive tomato pest, Phthorimaea absoluta (tomato leafminer), and the trichome-rich wild tomato, Solanum pennellii, we demonstrate that trichome produced acylsugars effectively inhibit the growth of endophagous P. absoluta larvae feeding inside leaves. High spatial resolution leaf- and frass-metabolite analysis by MALDI-MSI and Stimulated Raman Scattering microscopy revealed that trichome-synthesized acylsugars are translocated into the mesophyll tissues when larvae infest leaves. We identified an ATP-binding cassette (ABC) transporter, SpABCB5, as the mediator of this translocation and as an essential component of defense against leafminers. These data reveal that epidermal trichomes not only defend against free-living (ectophagous) herbivores through direct contact or rapid deposition of chemical defenses onto leaf surfaces, but also defend against endophagous leafminers by rapidly depositing chemical defenses into internal tissues. By delivering mines against leaf miners, trichomes offer new avenues for breeding crops with resistance to leafminers.

plant biology↗