Biology subjects

Wang, Z.-Y.

Publications and source records attributed to Wang, Z.-Y..

At least 19 recordsLinked to original sources

bioRxiv2026

Linking sugar sensing to immunity in plants via O-glycosylation

Interaction with microbes can reprogram metabolism and alter nutrient availability in plant cells. How metabolic changes modulate immune responses remains unknown. Here, we show that sugar-sensing O-glycosylation of immune-signaling kinases mediates metabolic regulation of immunity. Under sugar-replete conditions, the MAP kinase kinases (MKK4 and MKK5), key components of pattern-triggered immunity (PTI), are glycosylated with O-GlcNAc and O-fucose on their activation loops, blocking their phosphorylation by upstream kinases and thereby restricting PTI. Pathogen infection or sugar starvation reduces O-glycosylation of MKK4/5 and enhances immune signaling; these effects are reversed by GDP-fucose treatment, demonstrating that reduced sugar availability decreases O-fucosylation and enhances immune signaling in infected cells. Chemical inhibition of O-fucosylation enhances immunity and pathogen resistance in both Arabidopsis and tomato. Our findings establish O-glycosylation of MKKs as a metabolic rheostat that fine-tunes immune responses according to sugar availability during plant-microbe interactions, providing a new strategy for improving crop health.

plant biology↗

bioRxiv2025

Brassinosteroids promote sugar synthesis by inhibiting BIN2 phosphorylation of phosphoenolpyruvate carboxykinase

Sugar is both an essential energy source and the major substrate for cell wall biosynthesis during plant growth, yet how growth-promoting hormones regulate sugar synthesis remains unclear. Here, we show that the brassinosteroids (BRs) promote gluconeogenic and photosynthetic sugar synthesis by activating phosphoenolpyruvate carboxykinase (PCK), which catalyzes the conversion of oxaloacetate to phosphoenolpyruvate, a central step in primary metabolism. Arabidopsis BR-deficient mutants display reduced PCK1 activity and elevated phosphorylation at conserved Ser-62 and Thr-66 residues. BR treatment induces PCK1 dephosphorylation and activation, whereas the GSK3-like kinase BIN2 phosphorylates these sites, altering quaternary structure and inhibiting PCK1. Phospho-blocking mutations of Ser-62/Thr-66 confer BR-independent PCK1 activity and enhance seedling growth, while phosphomimetic mutations reduce PCK1 activity and impair seedling growth and establishment. BR also promotes PCK dephosphorylation and activation in photosynthetic leaves of maize and sorghum. Our study demonstrates that BR regulates primary metabolism via GSK3/BIN2-mediated phosphorylation of PCK, thereby promoting gluconeogenesis and photosynthesis.

plant biology↗

bioRxiv2025

Mitotic entry is controlled by the plant-specific phosphatase BSL1 and cyclin-dependent kinase B

Cell cycle regulation is well understood in opisthokonts (fungi and metazoans) but not in plants and Apicomplexa, as some cell cycle regulators are not conserved1-3. In opisthokonts, cell cycle progression requires dephosphorylation of cyclin-dependent kinase (CDK) by the CDC25 phosphatase4. Plants have no CDC25, and thus their mechanisms of cell cycle regulation remain elusive1,5,6. Here, we show that the BSL1 phosphatase dephosphorylates CDKB1 to promote mitotic entry in Chlamydomonas. Mutations of BSL1 or CDKB1 block mitotic entry after DNA replication. BSL1 shows dynamic localization through the cell cycle at the basal bodies, spindle poles, and cleavage furrow. CDKB1 is hyperphosphorylated at T14 and Y15 residues in the bsl1 mutant and in wild-type cells treated with DNA replication inhibitors. BSL1 binds to CDKB1 and dephosphorylates CDKB1 pT14/pY15 in vitro. Phospho-mimicking mutations of T14/Y15 inactivate CDKB1 function, whereas phospho-blocking mutations cause sensitivity to DNA replication inhibitors, which delay cytokinesis in wild-type cells more than cells expressing unphosphorylatable mutant CDKB1. These results indicate that CDKB1 T14/Y15 is phosphorylated to block mitotic entry before DNA replication is complete, and BSL1 dephosphorylates CDKB1 to promote mitosis. Our study demonstrates that BSL1, a phosphatase conserved in plants and Apicomplexa but absent in fungi and animals, is a CDKB1-activating mitosis-promoting factor that has evolved additional signaling functions in receptor kinase pathways in higher plants. One-Sentence SummaryBSL1 is a mitosis-promoting phosphatase that activates CDKB1 in plants.

plant biology↗

bioRxiv2025

Harnessing landscape genomics to evaluate genomic vulnerability and future climate resilience in an East Asia perennial

In this era of rapid climate change, understanding the adaptive potential of organisms is imperative for buffering biodiversity loss. Genomic forecasting provides invaluable insights into population vulnerability and adaptive potential under diverse climatic conditions, thereby facilitating management interventions, bolstering population resilience, and shaping germplasm conservation strategies tailored to specific species. Here we integrated population genomics and landscape genomics approaches, leveraging single-nucleotide polymorphisms obtained through whole-genome resequencing of 43 Rheum palmatum complex populations, to pinpoint adaptive variation and its significance in the context of future climates, delineate seed zones, and establish guidelines for ex situ germplasm conservation to capture the majority of existing adaptive diversity. Our analysis unveiled that the species complex comprised two distinct genetic clusters, exhibiting differential climate adaptation and genomic vulnerabilities across its distribution range. We also determined that the species range could be subdivided into three distinct seed zones, with varying sample requirements per seed zone corresponding to differed conservation efforts. Overall, our findings provide a genome-wide perspective on climate adaptation and valuable insights into germplasm conservation strategies aimed at enhancing population resilience in future climates, serving as a blueprint for restoration plans of other vulnerable species.

evolutionary biology↗

bioRxiv2025

Next-Generation Mapping of the ACINUS-Mediated Alternative Splicing Machinery and Its Regulation by O-glycosylation in Arabidopsis

Alternative splicing (AS) is a key mechanism of gene regulation, but the full repertoire of proteins involved and the regulatory mechanisms governing this process remain poorly understood. Using TurboID-based proximity labeling coupled with mass spectrometry (PL-MS), we comprehensively mapped the Arabidopsis AS machinery, focusing on the evolutionarily conserved splicing factor ACINUS, its paralog PININ, and the stable interactor SR45. We identified 298 high-confidence components, including both established and novel interactors, providing strong evidence that alternative splicing is coupled to transcription and that multiple RNA processing steps occur simultaneously in plants. Bioinformatic analysis reveals high redundancy, conserved mechanisms, and unique plant-specific features. Selected known and novel interactors were validated by AS readouts and phenotypic analysis, which also revealed a coordinated influence on splicing. Furthermore, a systematic evaluation of O-glycosylation double mutants revealed that SECRET AGENT (O-GlcNAc transferase) and SPINDLY (O-fucose transferase) modulate AS through both ACINUS-dependent and -independent pathways. Our results reveal the conserved as well as plant-specific AS regulatory network and highlight the global role of sugar modification in RNA processing.

plant biology↗

bioRxiv2024

Peptide Information Compression Technology (PICT): A New Frontier in Therapeutic Peptide Discovery

Therapeutic peptides hold tremendous market potential, yet the discovery methods for active peptides lag considerably behind those for small molecules and biological macromolecule drugs. Due to their respective limitations, traditional peptide compound synthesis and display libraries fail to meet the growing demands of the peptide drug market. Here, we introduce a novel Peptide Information Compression Technology (PICT) and, based on this technology, a large-scale physical peptide library and its accompanying high-throughput screening (HTS) platform. By screening for inhibitors of TSLP/TSLPR/IL7R and antagonists of MC3R at both the molecular and cellular levels, we have identified active molecules in the single-digital micromolar and nanomolar ranges, respectively. This demonstrates the immense application value of Peptide Information Compression Technology in the efficient discovery of peptide drugs.

molecular biology↗

bioRxiv2024

Direct Nuclear Delivery of Proteins on Living Plant via Partial Enzymatic Cell Wall Digestion

While many variations of protein delivery methods have been described, it can still be difficult or inefficient to introduce exogenous proteins into plants. A major barrier to progress is the cell wall which is primarily composed of polysaccharides and thus only permeable to small molecules. Here, we report a partial enzymatic cell wall digestion-mediated uptake method that efficiently delivers protein into the nucleus of plant cells. Such a method allowed efficient nuclear delivery of GFP proteins into Arabidopsis root cells throughout all cell layers. This study establishes that a partial enzymatic cell wall degradation could enable a myriad of plant biotechnology applications that rely on functional protein delivery into walled plant cells.

bioengineering↗

bioRxiv2024

Hsa_circ_0001304 promotes vascular smooth muscle cell autophagy and neointimal hyperplasia through the YTHDF2/mTOR axis

IntroductionAberrant autophagy in vascular smooth muscle cells (VSMCs) is associated with the progression of cardiovascular diseases. Recently, circular RNAs (circRNAs) have gradually been reported to regulate autophagy in VSMCs. ObjectivesThis study aims to investigate the role of hsa_circ_0001304 in VSMC autophagy and its underlying mechanism. MethodsThe combined use of dual-luciferase reporter gene assay, MeRIP-qRT-PCR, RIP-qRT-PCR, etc., was performed to verify the regulatory axis, hsa_circ_0001304/miR-636/YTHDF2/mTOR. Cell autophagy detection was performed to uncover the role of hsa_circ_0001304 on VSMC autophagy. The mouse carotid artery ligation model was conducted to assess the role of hsa_circ_0001304 on vascular neointimal hyperplasia. ResultsHsa_circ_0001304 acts as a sponge for miR-636, leading to an increase in the protein levels of YTHDF2. Subsequently, the YTHDF2 promotes the degradation of mTOR mRNA by binding to the latters m6A modification sites. Thus, by regulating the miR-636/YTHDF2/mTOR axis, hsa_circ_0001304 activates VSMC autophagy, aggravating neointimal hyperplasia. ConclusionOur findings suggest that autophagy-related hsa_circ_0001304 could serve as a novel therapeutic target for neointimal hyperplasia-related cardiovascular diseases. Including spacesOur study documents a novel VSMC autophagy-related circRNA, namely circ-1304, which activates VSMC autophagy through the miR-636/YTHDF2/mTOR axis, thereby exacerbating neointimal hyperplasia. Targeting autophagy-related circ-1304 may contribute to the treatment of neointimal hyperplasia-associated cardiovascular diseases.

molecular biology↗

bioRxiv2023

Nuclear Pyruvate Dehydrogenase Complex Regulates Histone Acetylation and Transcriptional Regulation in the Ethylene Response

Ethylene plays its essential roles in plant development, growth, and defense responses by controlling the transcriptional reprograming, in which EIN2-C-directed regulation of histone acetylation is the first key-step for chromatin to perceive ethylene signaling. But how the nuclear acetyl coenzyme A (acetyl CoA) is produced to ensure the ethylene-mediated histone acetylation is unknown. Here we report that ethylene triggers the accumulation of the pyruvate dehydrogenase complex (PDC) in the nucleus to synthesize nuclear acetyl CoA to regulate ethylene response. PDC is identified as an EIN2-C nuclear partner, and ethylene triggers its nuclear accumulation. Mutations in PDC lead to an ethylene-hyposensitivity that results from the reduction of histone acetylation and transcription activation. Enzymatically active nuclear PDC synthesize nuclear acetyl CoA for EIN2-C-directed histone acetylation and transcription regulation. These findings uncover a mechanism by which PDC-EIN2 converges the mitochondrial enzyme mediated nuclear acetyl CoA synthesis with epigenetic and transcriptional regulation for plant hormone response.

plant biology↗

bioRxiv2023

UPL3 Promotes BZR1 Degradation, Growth Arrest, and Seedling Survival under Starvation Stress in Arabidopsis

BRASSINAZONE RESISTANT 1 (BZR1) is a key transcription factor of the brassinosteroid signaling pathway but also a signaling hub that integrates diverse signals that modulate plant growth. Previous studies have shown that starvation causes BZR1 degradation, but the underlying mechanisms are not understood. Here we performed quantitative proteomic analysis of BZR1 interactome under starvation conditions and identified two BZR1-interacting ubiquitin ligases, BAF1 and UPL3. Compared to the wild type, the upl3 mutants show long hypocotyl and increased BZR1 levels when grown under sugar starvation conditions but not when grown on sugar-containing media, indicating a role of UPL3 in BZR1 degradation specifically under starvation conditions. The upl3 mutants showed a reduced survival rate after starvation treatment, supporting the importance of UPL3-mediated BZR1 degradation and growth arrest for starvation survival. Treatments with inhibitors of TARGET of RAPAMYCIN (TOR) and autophagy altered BZR1 level in the wild type but were less effective in upl3, suggesting that UPL3 mediates the TOR-regulated and autophagy-dependent degradation of BZR1. Further, the UPL3 protein level is increased posttranscriptionally by starvation but decreased by sugar treatment. Our study identifies UPL3 as a key component that mediates sugar regulation of hormone signaling pathways, important for optimal growth and survival in plants. IN A NUTSHELLO_ST_ABSBackgroundC_ST_ABSThe coordination between signaling pathways that monitor the levels of photosynthate and growth hormones is crucial for optimizing growth and survival, but the underlying mechanisms are not fully understood. When the sugar level is low, the BZR1 transcription factor of the brassinosteroid (BR) signaling pathway is degraded, and hence growth is attenuated to prevent starvation and enhance survival. When sugar is sufficient, sugar signaling inhibits BZR1 degradation and enables BR promotion of plant growth. The key component that mediates starvation-induced BZR1 degradation remains unknown. QuestionWhat proteins interact with BZR1 and mediate its degradation under sugar starvation? FindingWe performed immunoprecipitation mass spectrometry analysis of BZR1 in starvation-treated Arabidopsis and identified many BZR1-interacting proteins, including two E3 ligases UPL3 and BAF1. Genetic analysis showed that UPL3 plays a specific and prominent role in promoting autophagy-dependent BZR1 degradation and plant survival under sugar-starvation conditions. Next stepHow sugar-TOR signaling regulates UPL3 level remains to be studied in the future.

plant biology↗

bioRxiv2023

Brassinosteroid recruits FERONIA to safeguard cell expansion in Arabidopsis

Plant cell expansion is driven by turgor pressure and regulated by hormones. How plant cells avoid cell wall rupture during hormone-induced cell expansion remains a mystery. Here we show that brassinosteroid (BR), while stimulating cell elongation, promotes the plasma membrane (PM) accumulation of the receptor kinase FERONIA (FER), which monitors cell wall damage and in turn attenuates BR-induced cell elongation to prevent cell rupture. The GSK3-like kinase BIN2 phosphorylates FER, resulting in reduced FER accumulation and translocation from endoplasmic reticulum to PM. By inactivating BIN2, BR signaling promotes dephosphorylation and increases PM accumulation of FER, thereby enhancing the surveillance of cell wall integrity. Our study reveals a vital signaling circuit that coordinates hormone signaling with mechanical sensing to prevent cell bursting during hormone-induced cell expansion. One-Sentence SummaryBrassinosteroid recruits a cell wall integrity monitor to prevent growth-induced cell wall damage.

plant biology↗

bioRxiv2023

Rapid and accurate multi-phenotype imputation for millions of individuals

Deep phenotyping can enhance the power of genetic analysis, including genome-wide association studies (GWAS), but the occurrence of missing phenotypes compromises the potential of such resources. Although many phenotypic imputation methods have been developed, the accurate imputation of millions of individuals remains extremely challenging. In the present study, we developed a novel multi-phenotype imputation method based on mixed fast random forest (PIXANT) by leveraging efficient machine learning (ML)-based algorithms. We demonstrate that PIXANT runtime is faster and computer memory usage is less than that of other state-of-the-art methods when applied to the UK Biobank (UKB) data, suggesting that PIXANT is scalable to cohorts with millions of individuals. Our simulations with hundreds of individuals showed that PIXANT accuracy was superior to or comparable to the accuracy of the most advanced methods available. PIXANT was used to impute 425 phenotypes for the UKB data of 277,301 unrelated White British citizens. When GWAS was subsequently performed on the imputed phenotypes, 18.4% more GWAS loci were identified than before imputation (8,710 vs 7,355). The increased statistical power of GWAS identified novel positional candidate genes affecting heart rate, such as RNF220, SCN10A, and RGS6, suggesting that the use of imputed phenotype data from a large cohort may lead to the discovery of novel genes for complex traits.

bioinformatics↗

bioRxiv2023

SWI/SNF chromatin remodeling determines brassinosteroid-induced transcriptional activation

The brassinosteroid (BR) hormone is a central modulator of plant growth, development, and responses to stresses by activating or repressing the expression of thousands of genes through the transcription factor BRASSINAZOLE-RESISTANT 1 (BZR1) and its homologues. However, the molecular mechanism that determines the transcriptional activation versus repression activity of BZR1 remains largely unclear. Here, we show that BZR1-responsive transcriptional activation at thousands of loci requires the Switch defective/sucrose non-fermentable (SWI/SNF)-complexes-mediated chromatin accessibility regulation. BR-activated BZR1 controls the activation or repression of thousands of BZR1 target genes through reprograming genome-wide chromatin accessibility landscape in Arabidopsis thaliana. BZR1 physically interacts with the BRAHMA (BRM)-Associated SWI/SNF complexes (BAS), co-localizes with BRM on the genome, and enhances BRM occupancy at sites of increased accessibility by BR. Loss of BRM abrogates the capacity of BZR1 to increase but not decrease chromatin accessibility, blocks BR-induced hypocotyl elongation, and diminishes BZR1-mediated transcriptional activation rather than repression. Together, our work reveals that the BAS chromatin remodeling complex is a critical epigenetic regulatory partner in dictating BZR1-mediated transcriptional activation ability, thus providing a long sought mechanistic explanation for how BR signaling activates gene transcription in shaping diverse developmental programs. TeaserBZR1-responsive transcriptional activation activity at thousands of loci requires the SWI/SNF-complexes-mediated chromatin accessibility regulation.

plant biology↗

bioRxiv2023

Structure-based virtual screening identifies small molecule inhibitors of O-fucosyltransferase SPINDLY

Protein O-glycosylation is a nutrient-signaling mechanism that plays essential roles in maintaining cellular homeostasis across different species. In plants, SPINDLY (SPY) and SECRET AGENT (SEC) catalyze posttranslational modifications of hundreds of intracellular proteins by O-fucose and O-linked N-acetylglucosamine, respectively. SPY and SEC play overlapping roles in cellular regulation and loss of both SPY and SEC causes embryo lethality in Arabidopsis. Using structure-based virtual screening of chemical libraries followed by in vitro and in planta assays, we identified a SPY O-fucosyltransferase inhibitor (SOFTI). Computational analyses predicted that SOFTI binds to the GDP-fucose-binding pocket of SPY and competitively inhibits GDP-fucose binding. In vitro assays confirmed that SOFTI interacts with SPY and inhibits its O-fucosyltransferase activity. Docking analysis identified additional SOFTI analogs that showed stronger inhibitory activities. SOFTI treatment of Arabidopsis seedlings decreased protein O-fucosylation and caused phenotypes similar to the spy mutants, including early seed germination, increased root hair density, and defect in sugar-dependent growth. By contrast, SOFTI had no visible effect on the spy mutant. Similarly, SOFTI inhibited sugar-dependent growth of tomato seedlings. These results demonstrate that SOFTI is a specific SPY O-fucosyltransferase inhibitor and a useful chemical tool for functional studies of O-fucosylation and potentially for agricultural management.

plant biology↗

bioRxiv2021

15N metabolic labeling quantification workflow in Arabidopsis using Protein Prospector

Metabolic labeling using stable isotopes is widely used for the relative quantification of proteins in proteomic studies. In plants, metabolic labeling using 15N has great potential, but the associated complexity of data analysis has limited its usage. Here, we present the 15N stable-isotope labeled protein quantification workflow utilizing open-access web-based software Protein Prospector. Further, we discuss several important features of 15N labeling required to make reliable and precise protein quantification. These features include ratio adjustment based on labeling efficiency, median and interquartile range for protein ratios, isotope cluster pattern matching to flag incorrect monoisotopic peak assignment, and caching of quantification results for fast retrieval.

plant biology↗

bioRxiv2021

Loss of hepatic Lgr4 and Lgr5 promotes nonalcoholic fatty liver disease

Background & AimsThe Rspo-Lgr4/5-Znrf3/Rnf43 module is a master regulator of hepatic Wnt/{beta}-catenin signaling and metabolic zonation, but its impact on nonalcoholic fatty liver disease (NAFLD) remains unclear. We studied whether liver-specific loss of the Wnt/{beta}-catenin modulators Leucine-Rich Repeat-Containing G Protein-Coupled Receptor 4/5 (Lgr4/5) promotes nonalcoholic fatty liver disease (NAFLD). MethodsMice with liver-specific deletion of both receptors Lgr4/5 (Lgr4/5dLKO) were fed with normal diet (ND) or high fat diet (HFD). Livers of these mice were analyzed for lipid and fibrotic content by tissue staining and immunohistochemistry (IHC), and lipoproteins, inflammation and liver enzyme markers were measured in blood. Mechanistic insights into hepatic lipid accumulation were obtained by using ex vivo primary hepatocyte cultures derived from the Lgr4/5dLKO mice. Lipid analysis of mouse livers was performed by mass spectrometry (MS)-based untargeted lipidomic analysis. ResultsWe demonstrated that liver-specific ablation of Lgr4/5-mediated Wnt signaling resulted in hepatic steatosis, impaired bile acid (BA) secretion and predisposition to liver fibrosis. Under HFD conditions, we observed progressive intrahepatic fat accumulation, developing into macro-vesicular steatosis. Serum lipoprotein levels in HFD-fed Lgr4/5dLKO mice were decreased, rather than increased, suggesting that accumulation of fat in the liver was due to impaired lipid secretion by hepatocytes. Our lipidome analysis revealed a severe alteration of several lipid species in livers of Lgr4/5dLKO mice, including triacylglycerol estolides (TG-EST), a storage form of bioactive free fatty acid (FA) esters of hydroxy FAs (FAHFAs). ConclusionsLoss of hepatic Wnt/{beta}-catenin activity by Lgr4/5 deletion led to deregulation of lipoprotein pathways, loss of BA secretion, intrinsic alterations of lipid homeostasis and the onset of NAFLD. Lay summaryThe Wnt/{beta}-catenin pathway plays an important role during development and tissue homeostasis. Loss of Wnt/{beta}-catenin activity in mouse liver leads to loss of liver zonation, but the impact on nonalcoholic fatty liver disease (NAFLD) remains unclear. We show that livers of mice developed steatosis upon deletion of the positive pathway regulators Lgr4/5. Livers of knock-out (KO) mice exhibited altered lipid composition due to impaired lipid secretion. Furthermore, livers of these mice developed a nonalcoholic steatohepatitis (NASH)-like phenotype and fibrotic features derived from activated hepatic stellate cells. Our data demonstrate a protective role of Wnt/{beta}-catenin pathway activity towards the development of NAFLD. HighlightsO_LIAbrogation of hepatic Wnt/{beta}-catenin activity and liver zonation upon Lgr4/5 deletion in mice led to hepatic steatosis. C_LIO_LILiver fat accumulation was caused by impaired lipid secretion from hepatocytes. C_LIO_LISteatotic livers contained increased levels of diverse lipid species, including polyunsaturated fatty acids and triglycerol-estolides. C_LIO_LIThese data confirmed that a decrease in Wnt/{beta}-catenin signaling led to the development of nonalcoholic fatty liver disease (NAFLD) in mice. C_LI

physiology↗

bioRxiv2021

The Nicotiana tabacum Mediator subunit MED25 regulates nicotine biosynthesis through interacting with the basic helix-loop-helix (bHLH) transcription factor NtMYC2s

Nicotine is one of the most important secondary metabolites in tobacco, and its biosynthesis can be induced by topping and jasmonic acid treatment. NtMYC2s play pivotal roles in the regulation of nicotine. The mediator server as a bridge betwen the transcription factors and RNA polymerase in order to facilitates transcription and functions in plants. However, the role of mediator in the regulation of nicotine biosynthesis remains unknown. In this study, we firstly identify the NtMED25 through homologous analysis. NtMED25 interacts with NtMYC2s through the MD region. Interestingly, the nicotine content is decreased in the the knock-down transgenic lines of NtMED25, and the expression levels of two nicotine biosynthesis genes, NtQPT2 and NtPMT2, are also reduced when compared with that in the wild-type plants. Furthermore, NtMED25 enhances the binding of NtMYC2a/ NtMYC2b to the promoter of NtPMT2 and NtQPT2, and then facilitates the nicotine biosynthesis. Therefore, our study revealed the function of mediator in the regulation of nicotine, and provide the insight role on the transcriptional regulation of plant secondary metabolites.

plant biology↗

bioRxiv2021

A data-driven method to learn a jump diffusion process from aggregate biological gene expression data

Dynamic models of gene expression are urgently required. Different from trajectory inference and RNA velocity, our method reveals gene dynamics by learning a jump diffusion process for modeling the biological process directly. The algorithm needs aggregate gene expression data as input and outputs the parameters of the jump diffusion process. The learned jump diffusion process can predict population distributions of gene expression at any developmental stage, achieve long-time trajectories for individual cells, and offer a novel approach to computing RNA velocity. Moreover, it studies biological systems from a stochastic dynamics perspective. Gene expression data at a time point, which is a snapshot of a cellular process, is treated as an empirical marginal distribution of a stochastic process. The Wasserstein distance between the empirical distribution and predicted distribution by the jump diffusion process is minimized to learn the dynamics. For the learned jump diffusion equation, its trajectories correspond to the development process of cells and stochasticity determines the heterogeneity of cells. Its instantaneous rate of state change can be taken as "RNA velocity", and the changes in scales and orientations of clusters can be noticed too. We demonstrate that our method can recover the underlying nonlinear dynamics better compared to parametric models and diffusion processes driven by Brownian motion for both synthetic and real world datasets. Our method is also robust to perturbations of data because it only involves population expectations.

bioinformatics↗