Search bioRxiv⌕ Search

Biology subjects

Guo, V.

Publications and source records attributed to Guo, V..

4 recordsLinked to original sources

PromptBio: A Multi-Agent AI Platform for Bioinformatics Data Analysis

PromptBio is a modular AI platform for scalable, reproducible, and user-adaptable bioinformatics analysis, powered by generative AI and natural language interaction. It supports three complementary modes of analysis designed to meet diverse research needs. PromptGenie is a multi-agent system that enables stepwise, human-in-the-loop workflows using prevalidated domain-standard tools. Within PromptGenie, specialized agents--including DataAgent, OmicsAgent, AnalysisAgent, and QAgent--collaborate to manage tasks such as data ingestion, pipeline execution, statistical analysis, and interactive summarization. DiscoverFlow provides integrated, automated workflows for large-scale multi-omics analysis, offering end-to-end execution and streamlined orchestration. ToolsGenie complements these modes by dynamically generating executable bioinformatics code for custom, user-defined analyses, enabling flexibility beyond standardized workflows. PromptGenie and DiscoverFlow leverage a suite of domain-specific tools, including Omics Tools for standardized omics pipelines, Analysis Tools for downstream statistical interpretation, and MLGenie for machine learning and multi-omics modeling. We present the design, capabilities, and validation of these components, highlight their integration into automated and customizable workflows, and discuss extensibility, monitoring, and compliance. PromptBio aims to democratize high-throughput bioinformatics through a large language model-powered, natural language understanding, workflow generation and agent orchestration.

bioinformatics↗

Single-Cell Resolution of Lineage Trajectories in the Arabidopsis Stomatal Lineage and Developing Leaf

Dynamic cell states underlie flexible developmental programs, such as with the stomatal lineage of the Arabidopsis epidermis. Initial stages of the lineage feature asynchronous and indeterminate divisions modulated by environmental cues, enabling cell fate flexibility to generate the requisite density and pattern of stomata for a given environment. It remains unclear, however, how flexibility of cell fates is controlled. Here, we uncovered distinct models of cell state differentiation within Arabidopsis leaf tissue by leveraging single-cell transcriptomics and molecular genetics. Our findings resolved underlying heterogeneity within cell states of the flexible epidermal stomatal lineage, which appear to exist along a continuum, with progressive cell specification. Beyond the early stages of the lineage, we discovered that the core transcriptional regulator SPEECHLESS is required for cell fate commitment to yield stomatal guard cells. Overall, our work has refined the stomatal lineage paradigm and uncovered progressive cell state decisions along lineage trajectories in developing leaves.

plant biology↗

Redirected tropisms of extracellular vesicles and exomeres yield distinct biodistribution profiles

Extracellular particles (EP) including extracellular vesicles (EVs) and exomeres have been shown to play significant roles in diseases and therapeutic applications. However, their spatiotemporal dynamics in vivo have remained largely unresolved in detail due to the lack of a suitable method. We therefore created a bioluminescence resonance energy transfer (BRET)-based reporter, PalmGRET, to enable pan-EP labelling ranging from exomeres (< 50 nm) to small (< 200 nm) and medium and large (> 200 nm) EVs. PalmGRET emits robust, sustained signals and allows the visualization, tracking and quantification of the EPs from whole-animal to nanoscopic resolutions under different imaging modalities, including bioluminescence, BRET and fluorescence. Using PalmGRET, we show that EPs released by lung metastatic hepatocellular carcinoma (HCC) exhibit lung tropism with varying distributions to other major organs in immunocompetent mice. We further demonstrate that gene knockdown of lung-tropic membrane proteins, solute carrier organic anion transporter family member 2A1 (Slco2a1), alanine aminopeptidase (Cd13) and chloride intracellular channel (Clic1) decreases HCC-EP distribution to the lungs and yields distinct biodistribution profiles. We anticipate that EP-specific imaging, quantitative assays and detailed in vivo characterization to be a starting point for more accurate and comprehensive in vivo models of EP biology and therapeutic design.

cell biology↗

Sonogenetic modulation of cellular activities using an engineered auditory-sensing protein

Biomolecules that respond to different external stimuli enable the remote control of genetically modified cells. Chemogenetics and optogenetics, two tools that can control cellular activities via synthetic chemicals or photons, respectively, have been widely used to elucidate underlying physiological processes. These methods are, however, very invasive, have poor penetrability, or low spatiotemporal precision, attributes that hinder their use in therapeutic applications. We report herein a sonogenetic approach that can manipulate target cell activities by focused ultrasound stimulation. This system requires an ultrasound-responsive protein derived from an engineered auditory-sensing protein prestin. Heterogeneous expression of mouse prestin containing two parallel amino acid substitutions, N7T and N308S, that frequently exist in prestins from echolocating species endowed transfected mammalian cells with the ability to sense ultrasound. An ultrasound pulse of low frequency and low pressure efficiently evoked cellular calcium responses after transfecting with prestin(N7T, N308S). Moreover, pulsed ultrasound can also non-invasively stimulate target neurons expressing prestin(N7T, N308S) in deep regions of mice brains. Our study delineates how an engineered auditory-sensing protein can cause mammalian cells to sense ultrasound stimulation. Moreover, owing to the great penetration of low-frequency ultrasound ([~]400 mm in depth), our sonogenetic tools will serve as new strategies for non-invasive therapy in deep tissues of large animals like primates.

bioengineering↗