Biology subjects

Qu, Y.

Publications and source records attributed to Qu, Y..

At least 37 records · Page 2Linked to original sources

bioRxiv2026

Endogenous retroviral elements LTR8B and MER65 rewire PSG9regulation to control trophoblast syncytialization and pre-eclampsia risk

BackgroundUnderstanding the causes of the exceptional rate of evolution of the mammalian placenta is likely to aid the understanding of placental development and the aetiology of the human-specific pregnancy disorder pre-eclampsia (PE). As retroelements (REs) are often lineage-specific and known to be co-opted for placental functioning, here we consider the RE binding of GATA3 and DLX5, these transcription factors being dysregulated in PE, and their downstream consequences. MethodsMultiomics analyses identified the retroviral regulatory sequence LTR8B in the PSG gene array, as a contributor to expression diversification in the placenta. To characterize this genomic domain, we performed copy number variation analysis and whole-genome sequencing. Multiomics data was employed to identify loci that might act as an active chromatin loop boundary around the PSG region. CRISPR-Cas9 knockouts with aligned RNAseq and epigenetic mark data tested for trophoblast-specific cis-regulatory elements (CREs-enhancer and/or promoter sequences) of resulting loci. Functional assays were employed to characterize the phenotypic effects of a candidate locus. Structural analysis of PSG family members also identified an additional RE, MER65-int. RNA-seq and antibody staining was employed to consider polyadenylation and functional diversification. ResultsThe LTR8B CRE facilitates the binding of transcription factors (e.g., GATA3, DLX5, TFAP2A/C), resulting in a diversified PSG gene expression pattern within a primate-specific genomic region that exhibits high intraspecies variability. The LTR8B/PSG9 regulatory element influences other PSG family members. PSG9, unique among PSGs, produces both secreted and membrane-anchored isoforms, MER65-int providing alternative polyA signals, enabling the evolution of secreted PSG variants through the truncation of the ancestral CEACAM proteins transmembrane domain. The LTR8B/PSG9 locus regulates the differentiation of multinucleated trophoblasts (syncytialization) and, like chorionic gonadotropin and syncytin1, determines the identity of syncytiotrophoblasts. Notably, PSG9 is the most upregulated PSG in PE, with levels correlated with GATA3 and DLX5 levels. ConclusionsREs contribute to the structural and expression evolution of PSG genes, facilitating lineage-specific placental evolution. The LTR8B/PSG9 regulatory network plays a central role in syncytiotrophoblast differentiation. Given the association between DLX5/GATA3 dysregulation and elevated PSG9 levels, along with PSG9s expression in the first trimester, PSG9 shows potential as a predictive biomarker for PE.

developmental biology↗

bioRxiv2026

Autoimmune CD4+T cells Cause Meibomian Gland Dysfunction

Sjogren disease (SjD) is an autoimmune disease driven by autoreactive CD4+T cells that leads to an immune-mediated loss of lacrimal glands. Meibomian glands are lipid-producing glands in the eyelids that help prevent tear evaporation. While the role of T cells in lacrimal gland-mediated destruction is well established, it is unknown whether pathogenic T cells can cause MG dysfunction (MGD). Herein, we investigated whether autoreactive CD4+T cells induce MGD and characterized the pathophysiologic mechanisms using an adoptive transfer model. T cells were isolated from CD25KO (CD4KO) or wild-type (CD4WT) mice, transferred into Rag1KO mice. Further, CD4KO cells were co-adoptively transferred with WT regulatory T cells (CD4KO+TregsWT). Our results demonstrate that CD4KO recipients had MG dropout, CD4+IFN-{gamma}+ infiltration, increased MHC II presentation within the periglandular area, MG fibrosis, and decreased lipid production and upregulation of pathways related to inflammation, including Type II interferon signaling. Rag1KO, CD4WT, and CD4KO+TregsWT recipients exhibited minimal inflammation in the periglandular MG area. These results indicate that autoimmune CD4+T cells are sufficient to cause MGD, and healthy young regulatory T cells can prevent T-cell-mediated damage. Taken together, our findings provide mechanistic insights into the pathogenesis autoimmune SjD, and could impact how patients are managed in the clinic.

pathology↗

bioRxiv2026

De novo design of metalloproteases for targeted amyloid-β cleavage

De novo protein design has not yet achieved the creation of proteases capable of selectively cleaving any desired peptide bond within a native protein with high precision. Here, we report the use of the flow-based generative model Proteus2 to design metalloproteases by generating enzyme-substrate complexes conditioned on a target peptide sequence and a predefined catalytic motif. Our approach employs a two-step encapsulation strategy to create clamp-like metalloproteases that bind the target peptide in a manner that maximizes substrate sequence specificity. The generative process simultaneously optimizes the precise positioning of the target peptide bond in a catalytically competent configuration and accurately scaffolds the transition state catalytic residues--both essential for specific and efficient catalysis. Using this strategy, we designed zinc metalloproteases targeting three distinct cleavage sites within the aggregation-prone regions of amyloid-{beta} (A{beta}), a key pathogenic factor in Alzheimers disease. Experimental characterization validated five enzymes, each capable of precise cleavage at the intended sites with high specificity and minimal or undetectable activity on non-cognate substrates. On average, these enzymes accelerated peptide bond hydrolysis by more than 107-fold relative to the uncatalyzed reaction, and enabled efficient digestion of the A{beta} peptide into smaller segments when enzymes targeting different sites were combined. Cryo-EM structures of three designed enzymes in complex with A{beta} peptide, each targeting a distinct cleavage site, revealed close agreement with the design models. Together, these results demonstrate the potential of sequence-guided, generative approaches for developing programmable, sequence-specific proteolysis and lay the groundwork for future applications in basic research and therapeutic development.

synthetic biology↗

bioRxiv2025

Spent Mushroom Substrate Adsorbs Fusaric Acid to Protect the Cucumber Rhizosphere Microbiome and Alleviates Fusarium Wilt

Caused by Fusarium oxysporum f. sp. cucumerinum, cucumber Fusarium wilt threatens cucumber production worldwide. In addition to pesticides, using spent mushroom substrate (SMS) has a protective effect against Fusarium infection in cucumber, partly through effects on the microbiome. Fusaric acid (FA), a phytotoxic virulence factor secreted by Fusarium, disrupts both plant physiology and the rhizosphere microbial community. Herein, we investigated the relationship between SMS and this virulence factor. Bioassays demonstrated that SMS adsorbed FA both in culture supernatants and in soil. Adsorption behaviour conformed to the Langmuir-Freundlich isotherm model, with a maximum adsorption capacity of 52.72 g/g. Kinetics followed a pseudo-second-order model, indicating physical and chemical adsorption. Scanning electron microscopy showed that SMS had a porous surface, facilitating FA capture. Fourier transform infrared spectroscopy and chemical blocking assays were used to identify secondary amide groups as the key binding sites. In a dual-compartment pot system designed to isolate adsorption from other direct effects, SMS treatment significantly reduced the FA concentration in the cucumber rhizosphere and mitigated FA-induced disease aggravation. This lowered the disease index by up to 25%. Bacterial 16S metabarcoding showed that FA disrupted the rhizosphere bacterial diversity and community structure. However, when FA was adsorbed by SMS, the microbial diversity and community stability were restored. FA reduced the abundance of sensitive taxa such as Bacillus. Meanwhile, SMS-adsorbed FA preserved its relative abundance, suggesting a selective protective effect for FA-sensitive rhizobacteria. These findings indicate that SMS protects cucumber against Fusarium by alleviating FA toxicity toward beneficial microbes. Through FA adsorption, SMS amendment stabilised the rhizosphere microbial community and reduced disease incidence. This highlights the potential of SMS as a sustainable and microbiome-friendly strategy for managing soil-borne diseases.

microbiology↗

bioRxiv2025

Fluctuating flooding motivates the facilitation of a wetland invader: a probe into the stress gradient hypothesis

Stress gradient hypothesis proposes that the plant interaction tends to convert from competition to facilitation when facing accelerating stress. The present study aims to explore the interaction between two co-existing wetland plant invaders - Alternanthera philoxeroides and Myriophyllum aquaticum with exposure to flooding stress. Different plant assemblages including monospecific (single individual per species), homospecific (two individuals of same species) and heterospecific (two individuals of different species) treatments were subjected to different flooding regimes including mesic habitat, constant flooding and fluctuating flooding. The plant interaction was evaluated by biomass accumulation, biomass allocation and relative competition intensity index (RCI). We found that the biomass accumulation and allocation of A. philoxeroides were consistent across different treatments of community assemblage and flooding regime, while the root mass, biomass and root mass allocation of M. aquaticum significantly increased at the presence of A. philoxeroides. Moreover, the RCI of M. aquaticum decreased at the presence of A. philoxeroides. Especially, the RCI of M. aquaticum was 0.06 in the homospecific community, while that of M. aquaticum was -0.82 in the heterospecific treatment under fluctuating flooding condition. Overall, Alternanthera philoxeroides facilitated M. aquaticum, especially under fluctuating flooding condition, which complies with the stress gradient hypothesis. The water level drawdown can benefit the impedance of the growth of M. aquaticum and the deceleration of the co-invasion of A. philoxeroides and M. aquaticum.

ecology↗

bioRxiv2025

Single-Cell Immune Profiling Reveals Non-classical Monocyte-Driven Immunodepression in Tuberculosis Treatment Non-Responders

Sputum culture conversion (SCC) at 2 months is a critical predictor of tuberculosis (TB) treatment outcomes, yet the underlying immune alterations driving treatment non-response remain unclear. We performed single-cell RNA sequencing on peripheral blood mononuclear cells from 8 TB patients, stratified by 2-month SCC status, to characterize cellular heterogeneity and intercellular communication. Treatment non-responders exhibited marked expansion and terminal differentiation of non-classical monocytes with elevated TB progression risk signatures. These cells showed reduced outgoing but enhanced incoming signaling, prominently via IL-16 and TRAIL pathways, potentially amplifying regulatory T cell (Treg)-mediated immunosuppression. CD4 Tregs in non-responders engaged in intensified GALECTIN signaling toward CD8 cytotoxic T cells and mature NK cells, contributing to effector cell exhaustion. NK cell subsets, particularly mature NK c2, displayed increased inhibitory receptor expression and terminal differentiation states. Our findings delineate a dysregulated "non-classical monocyte -Treg -cytotoxic lymphocyte" axis in TB treatment failure, highlighting candidate biomarkers and host-directed therapeutic targets.

bioinformatics↗

bioRxiv2025

Host Phosphatase PPM1G Governs Influenza vRNP Homeostasis by Orchestrating NP Phosphorylation Dynamics and Autophagy

The influenza viral ribonucleoprotein (vRNP) serves as the machinery for viral RNA replication. It self - assembles from the RNA - dependent RNA polymerase (RdRp), viral RNA, and nucleoprotein (NP). During vRNP replication, NP proteins must rapidly switch between monomeric and polymeric states to sustain dynamic equilibrium, which relies on NP phosphorylation-dephosphorylation cycling and is crucial for viral nucleic acid replication. However, the regulatory mechanisms controlling this process remain poorly understood. In this study, we employed an RdRp/vRNP-targeted affinity mass spectrometry-based differential analysis method, discovered that the cellular protein phosphatase Mg2+/Mn2+-dependent 1G (PPM1G) is a phosphatase of NP and required for maintaining viral polymerase activity. Overexpression of PPM1G decreased viral replication. In ppm1g flox/flox-Sftpc Cre mice, lethal influenza infection led to survival and mild disease, as well as reduced lung viral loads and inflammation. These results suggest that PPM1G is a key host molecule for maintaining steady state of viral replication. PPM1G expression is upregulated upon influenza virus infection. This heightened expression occurs in response to increased viral protein production, simultaneously leading to elevated dephosphorylation of NP, which accelerates NP polymerization to promote viral replication. Meanwhile, surplus NP can be degraded through the ATG7 autophagylysosome pathway. Our research elucidates a mechanism that PPM1G maintains viral replication homeostasis by regulating NP status and fate.

microbiology↗

bioRxiv2025

BioLab: End-to-End Autonomous Life Sciences Research with Multi-Agents System Integrating Biological Foundation Models

Scientific discovery in the life sciences remains hindered by fragmented workflows, narrow-scope computational models, and inefficient links between in silico prediction and wet-lab validation. We present BioLab, a multi-agent system that integrates domain-specialized foundation models to automate end-to-end biological research. BioLab comprises eight collaborating agents, including a Planner, Reasoner, and Critic, orchestrated through a Memory Agent that enables iterative refinement via retrieval-augmented generation and a suite of 219 computational xBio-Tools spanning five biological scales (DNA, RNA, protein, cell, and chemical). These tools are built on the xTrimo Universe, a collection of 104 models derived from six foundation models (xTrimoChem, Protein, RNA, DNA, Cell, and Text), the majority of which achieve state-of-the-art (91-100% SOTA ratios) on domain benchmarks. Across standard reasoning tasks (PubMedQA, MMLU-Pro/Biology, GPQA-diamond), BioLab consistently outperformed leading large language models, including GPT-4o, Gemini-2.5, and DeepSeek-R1. Beyond benchmarks, BioLab autonomously executed a fully computational pipeline for de novo macrophage-targeting antibody design, progressing from target mining to multi-objective antibody optimization, where molecular dynamics simulations revealed structural mechanisms underlying enhanced affinity of optimized variants. Closing the computational-experimental loop, BioLab designed optimized antibodies (Pem-MOO-1, Pem-MOO-2) that achieved IC50 values of 0.01-0.016 nM, markedly surpassing the parental Pembrolizumab (0.027 nM) for PD-1. Functional assays confirmed enhanced pathway blockade and improved multi-parameter performance profiles. Together, these results establish BioLab as a generalizable framework for AI-native scientific discovery, demonstrating how multi-agent systems coupled with foundation models can autonomously generate, execute, and experimentally validate novel biological hypotheses.

bioinformatics↗

bioRxiv2025

Spatial transcriptomics identifies distinct domains regulating yield-related traits of the wheat ear

Cereal inflorescences are complex, highly ordered structures composed of grain-producing florets that form within specialised branches called spikelets. The spikelets of wheat are arranged in two alternating rows along a central rachis, in a pattern determined during early reproductive development. While several genes that control spikelet development have been identified, the molecular processes that regulate their morphology and the formation of supporting structures, such as meristems and the rachis, remain poorly understood. Here, we used spatial transcriptomics to investigate the dynamic transcriptional landscape of a wheat inflorescence during spikelet development. We identified two spatially distinct regions that regulate spikelet architecture, including a primordium region characterised by RAMOSA2 activity, and a boundary region that expresses ALOG1 and known regulators of bract suppression. Developmental assays indicate that spikelets differentiate from meristematic regions, which is accompanied by formation of central vascular regions of the rachis and inflorescence base that express genes controlling spikelet number. The combined spatial transcriptome and genetic data reveal key regulators of spikelet development, including target genes for improving spikelet number and yield.

plant biology↗

bioRxiv2025

From Family Relationship to Regulation: Parent-Child Amygdala Activation Similarity is Linked to Prefrontal Recruitment and Youth Emotional Adaptation

Extensive research highlights the importance of parent-child similarity at psychological, behavioral, and physiological levels in fostering childrens adaptation. While emerging studies have begun to explore neural similarity, little is known about the factors that influence parent- child neural similarity during adolescence or how such similarity may support youth emotional adaptation when coping with heightened uncertainty. The current study investigated the relations among family relationship quality, parent-youth neural similarity, and youth emotional adaptation using task-based fMRI. With 50 participants (25 parent-youth dyads; parent: Mage = 43.88{+/-}7.42 years, 72% female; youths: Mage = 11.16{+/-}2.85 years, 44% female), we found that higher parent-youth neural similarity in the amygdala activation patterns during emotionally uncertain situations was associated with better youths emotional adaptation, as indicated by lower levels of anxiety and depression and higher resilience. This neural similarity mediated the beneficial effects of positive family relationships on youths emotional adaptation. Additionally, amygdala activation similarity was associated with amygdala to dorsolateral prefrontal cortex (dlPFC) connectivity during uncertainty in youth, revealed by generalized psychophysiological interaction (gPPI) analyses. This amygdala-dlPFC connectivity, in turn, was linked to better emotional adaptation in youth. Importantly, these findings were specific to uncertainty-related bottom-up processing, rather than effortful top-down regulation processing or responses to certain aversive stimuli. These findings offer new insight into how relational and neural factors jointly shape youth emotional adaptation, and suggest that parent-child neural similarity in the amygdala may serve as a mechanism for supporting implicit emotion regulation, helping youth cope with uncertain situations. Significance StatementDuring adolescence, youth begin to expand their social worlds beyond the family, yet family relationships continue to shape how they navigate emotionally complex environments. How do these relationships influence youth brain function and emotional well-being? Using task-based fMRI, we found that greater parent-child neural similarity in the amygdala during emotionally uncertain situations is associated with youths lower anxiety and depression and greater resilience. This amygdala neural similarity was also linked to prefrontal engagement in youth during early arousal stage, supporting adaptive implicit regulation under uncertainty. These findings suggest that neural alignment between parents and youths may serve as a key mechanism by which positive family relationships promote emotional adaptation, highlighting the enduring role of family context in adolescent brain development.

neuroscience↗

bioRxiv2025

Far-Red Light in Early Growth Stages Boosts Lettuce Biomass and Preserves Anthocyanins

Background and AimsLight plays a dual role in plants, serving as both an energy source and a regulator of development from seedling to senescence. Recently, far-red (FR) radiation has gained attention in the controlled environment agriculture (CEA) science and grower community for its potential to enhance yield through canopy expansion and improved light capture, contributing positively to photosynthesis. This study explores how supplemental FR light promotes lettuce growth and morphology across weekly intervals as well as analyzing photosynthetic parameters, pigment accumulation, and anthocyanin gene expression. MethodsRed leaf lettuce (Lactuca sativa Red Fire) was grown in a commercial plant factory with artificial light for six weeks. 5000K white (W) light was maintained at 300 mol m-2 s-1, and FR, when supplemented, was added at 100 mol m-2 s-1 in addition to the 300 mol m-2 s-1 of W light. Four lighting treatments were tested under a 16 h photoperiod: (1) W for all 6 weeks ("W"), (2) 4 weeks of W followed by 2 weeks of supplemental FR ("W to W+FR"), (3) 4 weeks of FR supplementation followed by 2 weeks of only W ("W+FR to W"), and (4) W+FR for all 6 weeks ("W+FR"). Key ResultsThe shoot dry weight after 6 weeks in "W+FR", "W+FR to W" and "W to W+FR" was greater than "W". Both "W+FR" and "W+FR to W" showed a tendency for greater canopy expansion compared to "W" as well as "W to W+FR". There were no significant differences in stomatal conductance among the treatments. On the other hand, in both "W" and "W+FR to W" plants, CO2 assimilation rates were enhanced when FR light was supplemented during measurement, compared to when FR was not provided. Anthocyanin accumulation was greater in both "W" and "W+FR to W", consistent with the expression of key genes involved in the anthocyanin biosynthesis pathway, including anthocyanin synthase (ANS), flavanone 3-hydroxylase (F3H) and dihydroflavonol 4-reductase (DFR). ConclusionsThis study demonstrates that FR supplementation during the early growth stages of lettuce promotes biomass accumulation by enhancing both canopy expansion and photosynthetic activity, while maintaining high levels of functional compounds such as anthocyanins.

physiology↗

bioRxiv2025

A Patient-Specific 3D Printed Carotid Artery Model Integrating Vascular Structure, Flow and Endothelium Responses

The progression of atherosclerosis is driven by the interplay between vascular anatomy, hemodynamic forces, and endothelial responses. However, existing in vitro vascular models have yet to integrate all these elements into a cohesive, patient-specific system. Here, we present the first instance of direct 3D printing of a miniaturized, patient-specific carotid artery model that recapitulates anatomical-dependent hemodynamic changes and vascular cell remodeling. Phase-contrast MRI scans from a healthy donor were used to generate miniaturized 3D carotid artery models, which were analyzed via computational fluid dynamics (CFD) and particle imaging velocimetry (PIV) to validate the preservation of physiological hemodynamic properties. Using digital light processing (DLP) 3D printing, we fabricated the miniaturized carotid artery vessel using GelMA, containing embedded human aortic smooth muscle cells and an endothelialized lumen. Perfusion culture replicated physiological arterial shear stress of up to 10 dynes cm-{superscript 2}, resulting in differential endothelial cell alignment and inflammatory monocyte adhesion corresponding to laminar and turbulent flow regions within the carotid artery. This model serves as a powerful platform to investigate how anatomical variation influences susceptibility to atherosclerosis through its impact on local flow dynamics.

bioengineering↗

bioRxiv2025

Two parallel lineage-committed progenitors contribute to the developing brain

The hindbrain is a life-sustaining brain region. In one model, a common neural progenitor generates all brain regions. Here our studies of mouse embryos and human pluripotent stem cells (hPSCs) support a different model: two parallel brain progenitors emerge simultaneously during gastrulation, anterior neural ectoderm (forebrain/midbrain progenitor) and posterior neural ectoderm (hindbrain progenitor). Not only are they lineage-committed to respectively form forebrain/midbrain vs. hindbrain in vitro, but they also have diverging chromatin landscapes foreshadowing future forebrain/midbrain vs. hindbrain identities. Leveraging these differences, we differentiated hPSCs into hindbrain rhombomere 5/6-specific motor neurons, hitherto difficult to generate in vitro. We postulate the brain is a composite organ emanating from two lineage-restricted progenitors; these dual progenitors may be evolutionarily conserved across 550 million years from hemichordates to mammals.

developmental biology↗

bioRxiv2025

Microtubule curling as an efficient readout to uncover fundamental concepts of axonal cell biology

Nerve fibres (aka axons) are the slender, up-to-meter-long processes of nerve cells that wire nervous systems. These delicate structures must survive for an organisms lifetime, making them prime lesion sites in neurodegeneration. Their long-term maintenance requires the homeostasis of complex local cell biology upheld by motor protein-driven transport along microtubule bundles that run uninterrupted along axons. To gain an understanding of axonal homeostasis, we report and discuss here the functional loss of 105 genes from a wide range of cell biological processes using a standardised Drosophila primary neuron system. [~]40% of these gene deficiencies caused microtubule bundle disturbances referred to as microtubule-curling, which we use as an indicator of axonal atrophy. Our live imaging showed that microtubule-curling initiates in areas where axons widen, such as areas close to the soma, branch points or growth cones. In wild-type neurons, any initiated curling was contained, but it persisted as growing footprints in mutant curl-promoting conditions. Closer analyses of 20 curl-promoting conditions suggested a general classification into two groups: mutations affecting axonal physiology cause ROS-mediated microtubule-curling, whereas mutations causing motor hyperactivation or affecting microtubule-regulating proteins cause structurally induced ROS-independent curling. As will be discussed, our data provide consistent support for the previously proposed dependency cycle of local axon homeostasis model which can explain the long-standing conundrum that genes from a wide range of cell biological processes often have mutational links to the same class of inherited neurodegenerative disease.

cell biology↗

bioRxiv2025

Genome-Bench: A Scientific Reasoning Benchmark from Real-World Expert Discussions

In this short report, we present an automated pipeline tailored for the genomics domain and introduce Genome-Bench, a new benchmark constructed from over a decade of scientific forum discussions on genome engineering. Our pipeline transforms raw interactions into a reinforcement learningfriendly multiple-choice questions format, supported by 3000+ high-quality questionanswer pairs spanning foundational biology, experimental troubleshooting, tool usage, and beyond. To our knowledge, this is the first end-to-end pipeline for teaching LLMs to reason from scientific discussions, with promising potential for generalization across scientific domains beyond biology. The dataset is available at https://huggingface.co/datasets/Mingyin0312/Genome-Bench.

genomics↗

bioRxiv2025

Biomni: A General-Purpose Biomedical AI Agent

Biomedical research underpins progress in our understanding of human health and disease, drug discovery, and clinical care. However, with the growth of complex lab experiments, large datasets, many analytical tools, and expansive literature, biomedical research is increasingly constrained by repetitive and fragmented workflows that slow discovery and limit innovation, underscoring the need for a fundamentally new way to scale scientific expertise. Here, we introduce Biomni, a general-purpose biomedical AI agent designed to autonomously execute a wide spectrum of research tasks across diverse biomedical subfields. To systematically map the biomedical action space, Biomni first employs an action discovery agent to create the first unified agentic environment - mining essential tools, databases, and protocols from tens of thousands of publications across 25 biomedical domains. Built on this foundation, Biomni features a generalist agentic architecture that integrates large language model (LLM) reasoning with retrieval-augmented planning and code-based execution, enabling it to dynamically compose and carry out complex biomedical workflows - entirely without relying on predefined templates or rigid task flows. Systematic benchmarking demonstrates that Biomni achieves strong generalization across heterogeneous biomedical tasks - including causal gene prioritization, drug repurposing, rare disease diagnosis, micro-biome analysis, and molecular cloning - without any task-specific prompt tuning. Real-world case studies further showcase Biomnis ability to interpret complex, multi-modal biomedical datasets and autonomously generate experimentally testable protocols. Biomni envisions a future where virtual AI biologists operate alongside and augment human scientists to dramatically enhance research productivity, clinical insight, and healthcare. Biomni is ready to use at https://biomni.stanford.edu, and we invite scientists to explore its capabilities, stress-test its limits, and co-create the next era of biomedical discoveries.

bioinformatics↗

bioRxiv2025

A computational framework for mapping isoform landscape and regulatory mechanisms from spatial transcriptomics data

Transcript diversity including splicing and alternative 3 end usage is crucial for cellular identity and adaptation, yet its spatial coordination remains poorly understood. Here, we present SPLISOSM (SpatiaL ISOform Statistical Modeling), a computational framework for detecting isoform-resolution patterns from spatial transcriptomics data. SPLISOSM leverages multivariate testing to account for spot- and isoform-level dependencies, demonstrating robust and theoretically grounded performance on sparse data. In the mouse brain, we identify over 1,000 spatially variable transcript diversity events, primarily in synaptic signaling pathways linked to neuropsychiatric disorders, and uncover both known and novel regulatory relationships with region-specific RNA binding proteins. We further show that these patterns are evolutionarily conserved between mouse and human prefrontal cortex. Analysis of human glioblastoma highlights pervasive transcript diversity in antigen presentation and adhesion genes associated with specific microenvironmental conditions. Together, we present a comprehensive spatial splicing analysis in the brain under normal and neoplastic conditions.

bioinformatics↗

bioRxiv2025

A Novel Multilayer Cultivation Strategy Improves Light Utilization and Fruit Quality in Plant Factories for Tomato Production

Plant factories using artificial lighting are a promising solution to food security and urban agricultural challenges. However, cultivation of fruit-bearing crops such as tomatoes remains limited due to their high light demands, long growth periods, and tall plant structure. In this study, we aimed to develop an efficient cultivation system for tomatoes in a multilayer plant factory. Mini-tomatoes were hydroponically cultivated using white LEDs in a five-tier shelf system under two different cultivation methods. The conventional I-shaped method involved vertical growth on the top tier with downward lighting, while the novel S-shaped method trained each plant horizontally across the 2nd to 4th tiers with lateral lighting on each level. The S-shaped method enabled even light distribution, resulting in consistent photosynthetic rates throughout the canopy. In contrast, the I-shaped method suffered from strong light attenuation in the lower tiers, leading to reduced photosynthetic efficiency in shaded parts. Although total yield did not differ significantly between the two methods, the S-shaped method promoted earlier fruit maturation and improved fruit quality, including higher sugar content. Compared with greenhouse cultivation, plant factory conditions ensured stable temperature and lighting, leading to compact plant morphology, shorter internodes, and higher SPAD values. Moreover, fruit quality was more consistent year-round, with higher lycopene and sugar contents. This study demonstrates that the S-shaped cultivation system offers significant advantages in light use efficiency, plant management, and fruit quality. It represents a scalable approach for enhancing tomato production in plant factories and may facilitate the introduction of other high-light-demanding fruit crops into vertical farming systems.

plant biology↗