Biology subjects

Zhao, J.

Publications and source records attributed to Zhao, J..

At least 37 records · Page 2Linked to original sources

bioRxiv2026

A Hymenoptera-restricted gene mediating ant castes co-opts deeply conserved machinery to control organ size

Lineage-specific genes are widespread and have been implicated as phenotypic innovation inducers, but how they acquire complex developmental functions remains poorly understood. Ant queens and workers develop dramatically different organ sizes from identical genomes under juvenile hormone (JH) control, yet the molecular effectors translating JH signalling into caste-specific organ growth remain unknown. Here we identify torch, a Hymenoptera-restricted gene, as the most consistently gyne-biased and JH-responsive gene across 68 ant species. Knockdown of torch in virgin queens of Monomorium pharaonis produces a worker-like, multi-organ growth-restricted phenotype. Mechanistically, torch harbours an E-box-like motif activated by the JH receptor Gce-Tai and acts as a GA-repeat-binding transcription factor that regulates Hippo signalling, the deeply conserved organ-size control pathway in animals. Expressing torch heterologously in mice and a growth-restricted Drosophila background shows that the gene retained its general growth-promoting activity across more than 700 million years of animal evolution in lineages that lack the gene, establishing that its function is mediated through conserved rather than ant-specific machinery. A lineage-specific gene can therefore acquire complex morphogenetic function by co-opting ancient organ-size circuitry, providing a general route by which novel genes can drive phenotypic innovation.

evolutionary biology↗

bioRxiv2026

TomatoPGFM: A graph-conditioned foundation model for tomato pangenomes

Most genomic foundation models are pretrained on independent linear assemblies and therefore do not explicitly represent population-level segment sharing or local graph connectivity. We developed TomatoPGFM, a graph-conditioned model pretrained on 54.65 Gb of sequence from 66 tomato (Solanum spp.) accessions. Sequence tokens were conditioned on pangenome node attributes and local adjacency, and the model was optimised using masked language modelling and graph-feature reconstruction. To evaluate model responses to graph-conditioned input, we compared aligned, shuffled and disabled graph inputs in 25,000 windows from the training panel. Sequence-aligned graph input produced lower masked language modelling loss than graph-off at all five curriculum stages in both training-panel strata, while the shuffled perturbation generally yielded intermediate losses. We then assessed sequence-only transfer in Solanum sitiens LA1974 and S. lycopersicum MicroTom, neither of which was used for graph construction or pretraining. Frozen-probe AUROC values for gene-versus-intergenic and coding-sequence-versus-intergenic classification ranged from 0.8489 to 0.9593. TomatoPGFM produced higher AUROC point estimates than DNABERT-2 in all four comparisons. Enabling the zero-feature GraphAdapter pathway with adjacency messaging disabled changed throughput by less than 1% at 512-2,048 positions under the tested configuration. Together, these results show that TomatoPGFM responds consistently to sequence-aligned pangenome context in training-panel sequences and provides informative sequence representations for genic-region classification in accessions excluded from graph construction and pretraining.

bioinformatics↗

bioRxiv2026

Structural-functional calibration corrects single-neuron identity errors in volumetric calcium imaging

Volumetric calcium imaging is increasingly used to capture larger neuronal populations at higher throughput, but high-speed axial sampling can compromise single-neuron identity. Here we identify cross-plane identity duplication as a structured error in volumetric imaging: anisotropic axial blurring and plane-wise functional segmentation can repeatedly detect the same neuron across adjacent planes, creating duplicate functional nodes that inflate neuronal counts and distort network phenotypes. We developed Comprehensive Label-Guided (CLG) volumetric imaging, a structural-functional calibration framework that uses nuclear labels as stable three-dimensional identity anchors for calcium signals. CLG combines nuclear labeling, deep-learning-based 3D segmentation, anatomical registration and identity-guided trace reassignment. In larval zebrafish whole-brain recordings, CLG resolved ~30,000 redundant detections and reduced estimated neuronal counts by 37-46%. In mouse visual cortex, CLG consolidated ~40% of putative duplicates and recovered over 2,000 active neurons missed by calcium-only analysis. Across baseline and perturbed conditions, calibration stabilized graph-derived measurements of hub organization, long-range correlations and network resilience. CLG therefore defines an anatomy-constrained identity-calibration layer for reliable single-neuron-resolved volumetric imaging.

neuroscience↗

bioRxiv2026

Molecular dynamics descriptors for 1,079 post-translationally modified protein systems

Databases of post-translational modifications (PTMs) catalogue modified sites and increasingly add static structural context, but trajectory-derived descriptors remain scattered across specialised tools and general molecular dynamics archives. Dyna-MO PTM brings together 1,079 AlphaFold 3-seeded systems covering lysine acetylation, lysine and arginine monomethylation, and serine, threonine and tyrosine phosphorylation. Each system is linked to three completed 10 ns replicas generated with CHARMM36m and TIP3P, for 32.37 s of aggregate sampling. A 118-column table joins simulation and quality-control provenance with global relaxation measures, site solvent exposure, rotamers, secondary structure and ionic-contact proxies. Versioned identifiers connect the records to starting structures, trajectories, manifests and analysis scripts. Researchers can use the resource to filter PTM contexts, reproduce descriptors, prioritise longer simulations and evaluate trajectory-analysis or generative methods. The trajectories describe finite-window relaxation rather than equilibrium free energies, kinetics or matched PTM effects.

biophysics↗

bioRxiv2026

A self-amplifying microbial-abiotic sulfur relay drives field feasible bauxite residue remediation

Bauxite residue (BR), the haloalkaline byproduct of alumina refining, represents the largest and most costly environmental challenge facing the global aluminium industry, yet sustainable remediation has remained elusive because no rapid and field-feasible technology can overcome its recalcitrant alkalinity. Here, we establish a self-amplifying microbial-abiotic sulfur relay that drives rapid in situ acid generation and sustained dealkalization of BR across laboratory and glasshouse experiments and a field trial, where dealkalized residue subsequently supported spontaneous pioneer-plant colonization. Mechanistic assays and multi-omics analyses show that the relay is initiated by microbial reduction of elemental sulfur (S8) to HS- under oxygen-limited conditions. The resulting HS- abiotically attacks and solubilizes solid S_8, generating a mobile pool of polysulfides (Sx2-). In anoxic microsites, polysulfide reduction regenerates HS^-, which mobilizes additional S8 and amplifies sulfur turnover by increasing sulfur mobilization and bioavailability. In oxic microsites, Sx(2-) are abiotically converted to thiosulfate and reactive S0, which are subsequently microbially oxidized to sulfate and acidity. By coupling biotic reductive initiation and regeneration with abiotic sulfur mobilization and oxidation, followed by biotic terminal oxidation, this relay overcomes the low bioavailability of S8 and the constraints of extreme haloalkaline conditions, providing a low-cost, field-feasible strategy for efficient and sustained BR remediation.

microbiology↗

bioRxiv2026

TROP2-targeting chimeras (TRTACs) for tumor-selective membrane protein degradation and enhanced drug delivery

Extracellular targeted protein degradation (eTPD) systems typically utilize lysosome-targeting receptors (LTRs) to mediate internalization and lysosomal degradation of extracellular and membrane proteins. While multiple LTRs have been discovered, there remains a compelling need to seek for new LTRs, particularly those with clear clinical relevance, to expand the therapeutic potential of eTPD. Here we report trophoblast cell surface antigen-2 (TROP2), a clinically validated tumor-associated antigen, as a promising tumor-selective LTR. We engineer TROP2-targeting chimeras (TRTACs) by genetically fusing a TROP2-binding nanobody to nanobodies against specific target proteins. We show that TRTACs can induce tumor cell-selective degradation of diverse membrane proteins, including epithelial growth factor receptor (EGFR), human epithelial growth factor receptor 2 (HER2), and programmed death-ligand 1 (PD-L1). The EGFR-targeted TRTAC significantly inhibits tumor cell proliferation and shows potent antitumor activity in vivo. We further design TRTAC-drug conjugates (TRTAC-DCs) by attaching cytotoxic payloads to TRTACs, enabling targeted protein degradation together with enhanced drug delivery. TRTAC-DCs show significantly enhanced activity against HER2- and EGFR-positive tumors both in vitro and in vivo, with minimal toxicity observed in normal tissues. These findings establish TROP2 as a robust LTR and provide a versatile eTPD platform with profound translational potential for tumor treatment.

cell biology↗

bioRxiv2026

Concomitant post-translational repression of Arabidopsis PIP1 aquaporins upon the loss of major PIP2 isoforms

Aquaporins at the plant plasmalemma are divided into two highly conserved subclasses, PLASMA MEMBRANE INTINSIC PROTEINs 1 (PIP1) and PIP2. Arabidopsis thaliana encodes five PIP1 and eight PIP2 isoforms. Individual loss-of-function mutants had been employed for functional analyses. Here, we observe that the pip2;1 pip2;2 pip2;4 pip2;6 pip2;7 quintuple mutant defective of major PIP2 isoforms concomitantly leads to a strongly reduced PIP1 protein level. Lower order mutants pip2;1 pip2;2 and pip2;1 pip2;2 pip2;7 still harbor only 60% and 20% residual PIP1, respectively. This repression is established post-translationally, since neither PIP1s steady-state transcripts nor polysome-associated PIP1 mRNAs are suppressed by pip2;1 pip2;2 pip2;7. Thus, the two major pathways operating in eukaryotes for removal of aberrant proteins, ubiquitin proteasome system (UPS)-dependent ER-associated degradation (ERAD) and autophagy/vacuole-linked degradation, were assessed. Introgression of atg7 blocking autophagy-mediated degradation does not affect the PIP1 protein level of pip2;1 pip2;2 pip2;7. In contrast, introgression of ERAD loss-of-function mutations hrd1A hrd1B and dln1 into pip2;1 pip2;2 pip2;7 partially stabilizes its PIP1 protein level. PIP1 accumulates intracellularly upon pharmacological inhibition of proteasomal degradation by MG132. Nevertheless, the lack of a full PIP1 recovery by these means suggests the flexible operation of parallel ERAD components or unknown pathways. In conclusion, the essential dependence of PIP1 expression on PIP2 isoforms intrinsically interconnects the two PIP subclades at the protein level and will thereby affect their mutual functions. Significance statementPlasma membrane intrinsic proteins constituting the most homogenous plant aquaporin family are nonetheless split into two highly conserved subfamilies, PIP1 and PIP2. The loss of major Arabidopsis PIP2 isoforms does not lead to compensation by PIP1 members, but rather to PIP1s concomitant, post-translational repression. This dependence of PIP1 isoforms inevitably ties the two PIP subfamilies and their function.

plant biology↗

bioRxiv2026

Assembly and Conformational Dynamics of Insect Odorant Receptors

Insects rely on odorant receptors (ORs), tetrameric ligand-gated ion channels, to detect and discriminate a wide range of chemical cues. Within the insect OR family, composed of hundreds of OR subtypes, a conserved subunit termed odorant receptor co-receptor (Orco) is present in insect olfactory neurons. While Orco and some ORs can assemble into homo-tetramers, odor-activated channels are hetero-tetramers comprising Orco and an odor-specific OR. Cryogenic electron microscopy (cryo-EM) structures from heterologous expression systems revealed that Orco and OR assembled with a 3:1 (Orco:OR) stoichiometry. In these complexes, the OR subunit is solely responsible for ligand-recognition, whereas the Orco subunits form the majority of the ion conduction pathway and are key for assembly and membrane trafficking. Because Orco and OR can assemble in diverse stoichiometries, of which Orco(4) and OR(4) homo-tetramers, as well as Orco(3)/OR(1) hetero-tetramers, have been experimentally documented, we sought to investigate assembly and conformational dynamics of insect Orco/OR complexes. Here, using high-speed atomic force microscopy (HS-AFM), unique in providing simultaneous structural and temporal resolution, we find that Orco/OR complexes can reversibly transition into stable non-tetrameric oligomeric states, such as trimers and pentamers, through membrane-diffusive oligomer exchange. Furthermore, while all cryo-EM structures showed a fourfold symmetric or pseudo-symmetric conformation, we observed that tetrameric assemblies frequently adopt a symmetry-broken 'pinched' configuration, in addition to the canonical symmetric 'square' arrangement. Notably, ligand-binding modulates the 'pinching' kinetics in Orco/OR hetero-tetramers. Overall, these findings reveal key aspects of assembly and conformational dynamics of the insect OR family.

biophysics↗

bioRxiv2026

Time-Resolved Phenotyping Reveals Heterogeneous Rice Seed Germination Dynamics in Shallow-Water Culture

Germination percentage is an endpoint measure and therefore does not describe when an individual seed begins visible growth or how rapidly its radicle and plumule expand. We developed a time-resolved phenotyping workflow to quantify rice seed germination continuously in shallow-water culture. A single industrial camera moved along a 1 m rail and imaged three culture boxes at 1 h intervals for up to 80 h. The archive comprised 1,062 full-frame images and 6,372 seed-level repeated observations under the six-seed field-of-view configuration. A physical grid maintained seed identity through time and enabled individual regions of interest to be extracted. Whole-seed foregrounds were obtained with a pretrained U2-Net, and a masked RGB intensity rule separated newly emerging tissue from the darker hull. For each tracked seed, projected emerging-tissue area and interval growth rate were calculated. Three representative normally germinating seeds first showed measurable tissue at 48 h, yet subsequently followed distinct trajectories: final projected areas ranged from 2,605 to 4,700 pixels and peak interval growth rates ranged from 106.88 to 287.92 pixels h-1. B-1 accumulated 63.71% of its final visible area during 72-80 h, whereas B-3 accumulated 73.51% during 60-72 h. Thus, seeds with the same observed emergence interval can differ substantially in the timing and magnitude of post-emergence expansion. The workflow converts repeated images into biologically interpretable temporal phenotypes and provides a basis for nondestructive studies of rice seed vigor and germination heterogeneity.

plant biology↗

bioRxiv2026

tinyRNA-seq: An optimized approach to sequencing tiny RNAs and primitive RNA genomes

Very short RNAs play critical roles in modern biology, and are thought to have been crucial for genome replication during the origin of life. Next-generation sequencing is an essential tool for characterizing pools of small RNAs, but current library preparation methods suffer from strong size and sequence biases. Here we present tinyRNA-seq, an optimized library preparation method designed to minimize length- and sequence-dependent capture bias enabling the sequencing of RNA fragments as short as 2 nucleotides. We use degenerate adaptor regions to reduce ligation sequence bias and facilitate unique molecular identifier (UMI) installation. We benchmarked tinyRNA-seq against commercial kits using a model primordial RNA genome consisting of hundreds of defined oligonucleotides ranging from 2 to 12 nucleotides. tinyRNA-seq reproduced the input RNA distribution without the size and sequence bias of the commercial kits. tinyRNA-seq also enables the detection of de novo oligonucleotide generation, an important process for the origins of life. Applied to biologically derived small RNAs including miRNAs, piRNAs, and cityRNAs, tinyRNA-seq showed significantly lower capture bias and recovered a wider range of sequences than commercial kits. tinyRNA-seq may thus provide a more complete and quantitatively accurate representation of small RNAs from both biological and chemical sources. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=94 SRC="FIGDIR/small/743385v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@2fbb13org.highwire.dtl.DTLVardef@1a315eforg.highwire.dtl.DTLVardef@1f525bborg.highwire.dtl.DTLVardef@1801f25_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2026

Epitope-Focused Immunogens Confer Broad Protection against Coronaviruses

Variable regions in coronavirus spike dominate antibody responses elicited by infection or conventional vaccination and limit induction of broad neutralization. In contrast, conserved S2 elements, including the stem helix (SH) and fusion peptide proximal region (FPPR), are promising but subdominant targets of protective immunity. Here, we employed computational design to generate de novo epitope-focused immunogens that precisely present the SH and FPPR epitopes. Formulated as combinatorial immunogens, this vaccine elicited consistent serum responses with broad reactivity across known human coronaviruses and induced epitope-specific antibodies with broad neutralizing activity. As a heterologous boost, epitope-focused immunogens protected mice against challenge with phylogenetically distinct coronaviruses, including bat SARS-related RsSHC014-CoV and MERS-CoV, establishing a generalizable strategy for precision immune focusing and advancing universal coronavirus vaccine development.

bioengineering↗

bioRxiv2026

Pan-Peroxisome Proliferator-Activated Receptor Agonist IVA337 Alleviates Secondary Lymphedema via Inhibiting TGFβ/SMAD2/3 Signaling Pathway

Lymphedema is a chronic disease characterized by impaired lymph drainage and accumulation of protein-rich interstitial fluid, which progresses to develop irreversible fibrosis. Importantly, effective therapies and treatments are lacking to alleviate and mitigate the disease. The pathological inflammation and fibrogenesis underlying lymphedema prompted us to evaluate a preclinical medicine IVA337, a pan-peroxisome proliferator-activated receptor (PPAR) agonist that improves liver fibrosis in patients with metabolic dysfunction-associated steatohepatitis (MASH) by activating three PPAR isoforms (, {beta}/{delta}, {lambda}), which play critical roles in lipid metabolism, anti-inflammation responses, and anti-fibrogenesis. Here, we investigate the therapeutic effects of IVA337 during the early stage of surgery-induced secondary lymphedema in mice and explored the underlying mechanisms. IVA337 administration alleviated lymphedema progression, improved lymphatic drainage, reduced dermal thickness, and resolved lymphatic vessel dilation. Mechanistically, IVA337 suppressed the TGF{beta}/SMAD2/3 signaling pathway, reduced immune cells infiltration, and improves lymphatic vessels integrity. In human dermal lymphatic endothelial cells (HDLECs), IVA337 attenuated TGF{beta} induced SMAD2/3 phosphorylation and preserved the expression of cell junction Claudin5, reduced VE-Cadherin-stained cell-cell gaps. Collectively, our findings demonstrate that IVA337 protects against early stage lymphedema by inhibiting TGF{beta}/SMAD2/3-mediated inflammatory and fibrotic responses. This study provides a potential therapeutic strategy to improve lymphatic function during the early phase of lymphedema and prevent progressive fibrosis in patients with lymphedema and related disorders.

pathology↗

bioRxiv2026

A Chairside Multimodal Platform for Temporomandibular Joint Biomechanical Assessment: Technical Evaluation and Illustrative Application

BackgroundTemporomandibular joint (TMJ) biomechanics can be characterized by mandibular motion, masticatory muscle activity, and bite force generation. When acquired synchronously, these functional variables can serve as model-ready inputs for subject-specific computational analyses of internal joint mechanics. However, existing tools typically measure these signals using separate hardware and software platforms, limiting synchronized acquisition within a clinically practical chairside workflow. MethodsWe developed and technically evaluated a compact multimodal platform for chairside acquisition of TMJ functional data and demonstrated its analytical utility in an illustrative orthognathic surgery application. The platform integrates motion, bite force, muscle activity, acoustic, and event-timing measurements with software for real-time preview, protocol guidance, and synchronized export. We assessed technical performance and chairside feasibility and analyzed representative pre- and postoperative data from an orthognathic surgery patient using kinematic, force-control, and computational modeling workflows. FindingsMotion capture demonstrated submillimeter accuracy, with static and dynamic errors of approximately 0.04 mm and 0.12 mm. Bite force sensors showed excellent linearity (R{superscript 2} = 0.998). Chairside deployment required approximately 15 minutes each for setup and data collection. The illustrative case demonstrated that synchronized chairside data can support preoperative and postoperative kinematic analysis, bite force control capacity assessment, and estimation of TMJ disc stress. InterpretationThe proposed platform enables time-efficient chairside acquisition of synchronized, model-ready multimodal datasets for quantitative TMJ biomechanical assessment. This platform and workflow could support subject-specific biomechanical analysis and future clinical studies of temporomandibular joint function.

bioengineering↗

bioRxiv2026

Multiscale Biomechanical and Electrophysiological Modeling of Nociceptive Activation in Musculoskeletal Joint Disorders: Insights from the Temporomandibular Joint

Background and objectiveMusculoskeletal joint disorders often show inconsistent relationships between structural degeneration and nociceptive pain. Temporomandibular joint (TMJ) disc displacement represents a clinically relevant model for investigating the structure-function-pain relationship. This study aimed to develop a multiscale computational framework integrating biomechanics, three-dimensional (3D) neural morphology, and electrophysiology to quantitatively link TMJ structural alterations, biomechanical loading, and peripheral nociceptive activation. MethodsStrain distributions in the TMJ disc and retrodiscal tissue during mouth opening and clenching were computed in ArtiSynth under varying degrees of displacement. Human TMJ 3D nerve architecture was reconstructed using porcine TMJ nerve mapping data as an anatomical reference, and ion channel dynamics were implemented in NEURON. Model coupling was achieved by mapping biomechanical strain fields onto nociceptor membranes to simulate mechanosensitive currents and action potential propagation to the trigeminal ganglion. ResultsAnterior DDwoR induced a severity dependent strain pattern in the TMJ disc and retrodiscal tissue, including posterior redistribution, increased strain magnitude, prolonged activation, and broader retrodiscal tissue involvement. Displacements of 4, 6, and 8 mm produced larger mechanosensitive currents, broader terminal depolarization, and higher trigeminal firing rates during mouth opening (6, 18, and 28 Hz) and clenching (8, 20, and 28 Hz), whereas 0- and 2-mm displacements produced negligible neural activation. ConclusionsThis study establishes a multiscale biomechanical-electrophysiological framework linking TMJ structural alterations to peripheral nociceptive activation. The framework quantitatively connects macroscale strain patterns with microscale neural activation, suggesting that anterior disc displacement may amplify peripheral nociceptive signaling by increasing the overlap between elevated strain and densely innervated retrodiscal tissue.

bioengineering↗

bioRxiv2026

Bidirectional hybridization between Ulva prolifera and U. linza (Ulvophyceae, Chlorophyta): Evidence for compatibility and paternal chloroplast inheritance

Ulva prolifera and U. linza are closely related species, with abundant adult thalli and reproductive cells co-occurring extensively in time and space during the Yellow Sea green tides. Elucidating their hybridization compatibility is crucial for species delimitation, assessing interspecific gene flow, and evaluating the ecological impacts of green tides. Previous studies suggested asymmetric gamete compatibility (only U. prolifera mt+ x U. linza mt-), but lacked sex-linked markers to reliably identify hybrid diploids and their reproductive modes, and did not examine chloroplast inheritance. Here, we performed bidirectional crosses using sexual strains of different geographic origins from both parents, with sex-linked markers to quantify progeny genotypes, examine fertility and reproduction pathway of F1 hybrids, and trace chloroplast inheritance using the species-specific petB marker. Our results showed that: (1) F1 hybrids were obtained in both cross directions, with significantly higher frequency in the direct cross (U. linza mt+ x U. prolifera mt-), indicating no complete reproductive isolation in either direction; the biased compatibility likely reflected genetic background differences among the limited strain combinations in a single study. (2) A considerable number of germinated progeny arose from parthenogenesis of parental gametes. (3) F1 hybrids from both crosses could undergo meiosis to form gametes and develop into gametophytes; additionally, F1 from the reciprocal cross produced diploid spores for asexual reproduction, suggesting meiotic disturbance. (4) Chloroplasts were maternally inherited in selfing of U. prolifera parent, but in all F1 hybrids they were paternally inherited, indicating a potential reversal of the inheritance pattern due to interspecific hybridization. These findings provided new insights into the potential for genetic exchange between U. prolifera and U. linza.

genetics↗

bioRxiv2026

Semantic fragment representations for coordinate-free analysis of genomics data

Many genomic assays begin with individual DNA fragments, but standard analysis quickly collapses those molecules into counts over genomic intervals. Rich information carried by each fragment, including its sequence, fragment body, cleavage boundaries, and local flanking context, is lost in this process. This loss is especially apparent in mixed-source and heterogeneous samples, where individual fragments originate from disparate cell types and can retain information about their cell of origin. To address this, we present LEAF-1, a fragment-level foundation model pre-trained on approximately 58 billion fragments spanning bulk ATAC-seq, single-cell ATAC-seq, and cell-free DNA profiles, representing each DNA molecule as a point in a learned semantic space defined by sequence context, assay modality, and explicit cleavage-boundary tokens. In sparse scATAC-seq datasets, mean-pooled LEAF-1 embeddings readily classify human cell types from as few as [~]1,000 fragments per cell, with high-scoring fragments linked to cell-type-associated transcription-factor programs. Similarly, in cell-free DNA profiling, LEAF-1 outperformed state-of-the-art coordinate-binning strategies and general-purpose DNA language model baselines across cancer detection tasks. Applying attention-based multiple-instance learning to LEAF-1 embeddings further improved cancer detection, reaching an area under the receiver operating characteristic (ROC) curve (AUC) of 0.95. This pan-cancer model generalizes beyond cancer types it is trained on, as we show by profiling plasma samples from clear cell renal cell carcinoma patients and healthy volunteers and applying the frozen classifier without retraining, achieving an AUC of 0.83. These results show that semantic learning over individual DNA fragments preserves biochemical, cell-associated, and disease-associated signals that are otherwise lost during coordinate-based aggregation.

genomics↗

bioRxiv2026

A gap-free telomere-to-telomere genome of the purple-pericarp rice landrace Mojiang ZN65 resolves transposon-driven structural variation at the pericarp-pigmentation loci

Background: Black and purple pericarp in rice requires activation of the basic helix-loop-helix (bHLH) regulator Kala4/OsB2, and the known black-rice allele is a complex promoter rearrangement. Such repeat-embedded alleles can be difficult to resolve in fragmented assemblies, and for many pigmented landraces it remains unclear whether they carry that allele or structurally different ones. We asked three questions about the purple-pericarp landrace Mojiang ZN65: what is the structure of its Kala4/OsB2 upstream region; how frequent is gain of its upstream block in a rice diversity panel, and do the accessions with that gain share its junction; and how is it distributed relative to a second regulatory variant, a duplicated repeat in the OsKala3 promoter. Results: We assembled a gap-free telomere-to-telomere genome of ZN65 (395.1 Mb; all 24 telomeres; consensus quality value 53.6; 99.6% complete Benchmarking Universal Single-Copy Orthologues; indica), in which the flavonoid pathway showed no pathway-wide copy-number expansion. Upstream of Kala4/OsB2, a ~5.87-kb segment (block A) is present in three non-tandem copies, spanned as single molecules by three ultra-long Nanopore reads (115,450 bp); each of 33 other assemblies yielded a single homologous hit (10 of them coverage- or divergence-limited). This arrangement differs from the canonical black-rice Kala4 allele. Among 533 accessions of the 3,000 Rice Genomes panel, read depth detected block A gain in four accessions (three at three or more copies, 0.56%; one at two). All four carry the ZN65 junction at the same base, and three carry a pigment term in their variety names from a lexicon fixed in advance (Fisher's exact test, P = 0.0023). All four also have OsKala3 promoter-repeat read depth consistent with the two-unit configuration reported for black-pericarp cultivars, a state found in 1.9% of the panel. Conclusions: ZN65 carries a rare Kala4/OsB2 structural variant whose junction is shared with other accessions named as pigmented rice and which, in this panel, occurs only in accessions whose OsKala3 promoter-repeat read depth indicates duplication. Its effect on pigmentation remains to be tested with measured pericarp phenotypes and functional assays.

plant biology↗

bioRxiv2026

Spatial co-expression and cell-cell communication inference from spatially resolved transcriptomics with CONCISE

Cell-cell communication is fundamental to tissue organization, homeostasis, and disease progression. Recent advances in spatial transcriptomics provide unprecedented opportunities to systematically characterize ligand-receptor interactions directly within intact tissues. However, robust inference of spatial ligand-receptor interactions remains challenging because intrinsic features of spatial transcriptomics data, including spatial autocorrelation, variation in total molecular counts, and measurement errors, can induce spurious spatial co-expression and lead to inflated false-positive results. Most existing methods do not adequately account for these confounding factors, limiting the reliability of inferred cellular communication. Here, we present CONCISE, a statistical method for spatially constrained co-expression and ligand-receptor interaction inference that jointly models spatial autocorrelation, variation in total molecular counts, measurement errors, and spatial proximity constraints. CONCISE combines efficient moment-based parameter estimation with analytical hypothesis testing, enabling fast and statistically rigorous inference without restrictive distributional assumptions. Through extensive simulations, real-data permutation experiments, and biologically motivated negative-control analyses across different spatial transcriptomics platforms, we show that most existing methods presented inflated false-positive rates, whereas CONCISE achieved well-calibrated inference, robust false-positive control, and improved detection power. Application of CONCISE to high-resolution MERFISH and CosMx datasets from intestinal inflammation and non-small cell lung cancer further highlights its biological utility in disease contexts. CONCISE uncovered inflammation-associated fibroblast-specific interactions during intestinal inflammation and delineated complex tumor-immune and tumor-stromal signaling networks within the tumor microenvironment.

bioinformatics↗