Biology subjects

Zhao, Y.

Publications and source records attributed to Zhao, Y..

At least 577 records · Page 32Linked to original sources

bioRxiv2023

GeneCompass: Deciphering Universal Gene Regulatory Mechanisms with Knowledge-Informed Cross-Species Foundation Model

Deciphering the universal gene regulatory mechanisms in diverse organisms holds great potential to advance our knowledge of fundamental life process and facilitate research on clinical applications. However, the traditional research paradigm primarily focuses on individual model organisms, resulting in limited collection and integration of complex features on various cell types across species. Recent breakthroughs in single-cell sequencing and advancements in deep learning techniques present an unprecedented opportunity to tackle this challenge. In this study, we developed GeneCompass, the first knowledge-informed, cross-species foundation model pre-trained on an extensive dataset of over 120 million single-cell transcriptomes from human and mouse. During pre-training, GeneCompass effectively integrates four types of biological prior knowledge to enhance the understanding of gene regulatory mechanisms in a self-supervised manner. Fine-tuning towards multiple downstream tasks, GeneCompass outperforms competing state-of-the-art models in multiple tasks on single species and unlocks new realms of cross-species biological investigation. Overall, GeneCompass marks a milestone in advancing knowledge of universal gene regulatory mechanisms and accelerating the discovery of key cell fate regulators and candidate targets for drug development.

bioinformatics↗

bioRxiv2023

Enhancing plant photosynthesis through activating cells deficient in photosynthetic apparatus

Much efforts have been devoted to identify options to improve plant photosynthetic capacity. Most of these engineering focuses more on enhancing photosynthetic capacity of the mesophyll cells. In this study, we specifically expressed CYTOKININRESPONSIVE GATA FACTOR 1 (CGA1) in the vascular bundle and bundle sheath cells (ProGLDPA: CGA1) which generally have low photosynthetic capacity. The introduction of CGA1 resulted in increased numbers and sizes of chloroplasts in both bundle sheath and vascular bundle, without noticeable difference in these properties in mesophylls. Additionally, compared with wild type (WT), transgenic lines showed enhanced development of mitochondria and peroxisomes. Leaf photosynthetic rates in these transgenic lines were higher than those in WT, especially under high light. Furthermore, the amount of RuBisCO, Vcmax, Jmax, and the number of starch granules were also significantly increased in the transgenic lines, which led to about 20% increase in biomass. Remarkably, the CO2 compensation point of ProGLDPA: CGA1 decreased compared with WT, resembling the characteristics of proto-Kranz during C4 evolution. All these results indicated that enhancing photosynthetic properties of vascular bundle and bundle sheath cell is an effective approach to improve leaf photosynthesis, and highlighted that utilization of the cell lacking photosynthetic capacity is a promising way to improve plant photosynthesis for greater capacity.

plant biology↗

bioRxiv2023

Bio-inspired mineralization collagen induce fibrocartilage regeneration after tendon-bone injury by activating Gli1+Dkk3+ progenitor cells

A fibrocartilaginous connection between the tendon and bone, plays a critical role in transferring force from muscle to bone to enable joint movement. However, due to the high mechanical stress it experiences, the enthesis is vulnerable to injury and incapable of regenerating. The spatial relationship and functional basis of the principal components of the fibrocartilage - mineral and collagen - have not been clearly elucidated, which is a significant remaining gap in reconstructing complex architectures for promoting interface tissue regeneration. Here, using three-dimensional electron tomography imaging and high-resolution two-dimensional electron microscopy, we discover that mineral particles form a continuous cross-fibrillar phase within the fibrocartilage region. By developing a "floating mineralization" system, we fabricate a three-layer hydrogel that mimics the hierarchical nano- to micro-scale structure of tendon-bone interface (TBI). The middle layer is noteworthy for its resemblance to the nanostructure of fibrocartilage and its superior ability to induce mineralized fibrochondrogenesis in vitro. Based on motor function analysis, imaging diagnosis, histological staining, immunofluorescence staining, and biomechanics performance, we demonstrate that in situ transplantation of the gradient hydrogel achieved tendon-fibrocartilage-bone synchronous regeneration and result in 68% maximum mechanical recovery at 8-week postoperation. Single-cell RNA sequencing analysis reveals that a unique atlas of in situ stem/progenitor cells is generated during the TBI healing in vivo. Notably, the bio-inspired hydrogel microenvironment drived endogenous Gli1+Dkk3+ progenitor cells, playing a key role in TBI regeneration. Therefore, we have successfully decoded and reconstructed the nanostructure of fibrocartilage, which has great potential in TBI regeneration.

bioengineering↗

bioRxiv2023

Geranylgeranyl pyrophosphate (GGPP) is associated with hepatic lipid accumulation and insulin resistance in MAO by prenylating Perilipin4

Metabolically Abnormal Obesity (MAO) is characterized by hepatic steatosis and type 2 diabetes (T2D), in contrast to Metabolically Healthy Obesity (MHO). In this study, we investigated the role of hepatic geranylgeranyl pyrophosphate (GGPP), a metabolite of the mevalonate (MVA) pathway, in regulating the differences in lipid metabolism between MAO and MHO. Our findings revealed that GGPP levels were significantly elevated in individuals with MAO, and deficiency of GGPP in the liver ameliorated the defects associated with MAO. Furthermore, we discovered that the prenylation of the lipid droplet-associated protein Perilipin 4 by GGPP enhances the formation of large lipid droplets, thereby exacerbating hepatic lipid accumulation and insulin resistance. Notably, the inhibitor DGBP, targeting the GGPP synthase Ggpps, effectively attenuated the traits of MAO, offering novel insights into the treatment of this condition.

pathology↗

bioRxiv2023

Multiscale effective connectivity analysis of brain activity using neural ordinary differential equations

Neural mechanisms and underlying directionality of signaling among brain regions depend on neural dynamics spanning multiple spatiotemporal scales of population activity. Despite recent advances in multimodal measurements of brain activity, there is no broadly accepted multiscale dynamical models for the collective activity represented in neural signals. Here we introduce a neurobiological-driven deep learning model, termed multiscale neural dynamics neural ordinary differential equation (msDyNODE), to describe multiscale brain communications governing cognition and behavior. We demonstrate that msDyNODE successfully captures multiscale activity using both simulations and electrophysiological experiments. The msDyNODE-derived causal interactions between recording locations and scales not only aligned well with the abstraction of the hierarchical neuroanatomy of the mammalian central nervous system but also exhibited behavioral dependences. This work offers a new approach for mechanistic multiscale studies of neural processes. Author SummaryMulti-modal measurements have become an emerging trend in recent years due to the capability of studying brain dynamics at disparate scales. However, an integrative framework to systematically capture the multi-scale nonlinear dynamics in brain networks is lacking. A major challenge for creating a cohesive model is a mismatch in the timescale and subsequent sampling rate of the dynamics for disparate modalities. In this work, we introduce a deep learning-based approach to characterize brain communications between regions and scales. By modeling the continuous dynamics of hidden states using the neural network-based ordinary differential equations, the requirement of downsampling the faster sampling signals is discarded, thus preventing from losing dynamics information. Another advantageous feature of the proposed method is flexibility. An adaptable framework to bridge the gap between scales is necessary. Depending on the neural recording modalities utilized in the experiment, any suitable pair of well-established models can be plugged into the proposed multi-scale modeling framework. Thus, this method can provide insight into the brain computations of multi-scale brain activity.

neuroscience↗

bioRxiv2023

Robust Small Molecule-Aided Cardiac Reprogramming Systems Selective to Cardiac Fibroblasts

Direct cardiac reprogramming to induce cardiomyocyte-like cells, e.g. by GMT (Gata4, Mef2c and Tbx5), is a promising route for regenerating damaged heart in vivo and disease modelling in vitro. Supplementation with additional factors and chemical agents can enhance efficiency but raises concerns regarding selectivity to cardiac fibroblasts and complicates delivery for in situ cardiac reprogramming. Here, we screened 2000 chemicals with known biological activities and found that a combination of 2C (SB431542 and Baricitinib) significantly enhances cardiac reprogramming by GMT. Without Gata4, MT (Mef2c and Tbx5) plus 2C could selectively reprogram cardiac fibroblasts with enhanced efficiency, kinetics, and cardiomyocyte function. Moreover, 2C significantly enhanced cardiac reprogramming in human cardiac fibroblasts. 2C synergistically enhances cardiac reprogramming by inhibiting Alk5, Tyk2 and downregulating Oas2, Oas3, Serpina3n and Tgfbi. 2C enables selective and robust cardiac reprogramming that can greatly facilitate disease modelling in vitro and advance clinical therapeutic heart regeneration in vivo.

cell biology↗

bioRxiv2023

Transcriptomics analyses of the LRRK2 protein interactome reveal distinct molecular signatures for sporadic and LRRK2 Parkinson's Disease

Mutations in the LRRK2 gene are the most common genetic cause for familial Parkinsons Disease (LRRK2-PD) and an important risk factor for sporadic PD (sPD). Multiple clinical trials are ongoing to evaluate the benefits associated with the therapeutical reduction of LRRK2 kinase activity. In this study, we described the changes on transcriptomic profiles (whole blood mRNA levels) of LRRK2 protein interactors in the sPD and LRRK2-PD cases as compared to healthy controls with the aim of comparing the two PD conditions. We went on to model the protein-protein interaction (PPI) network around LRRK2, which was weighted to reflect the transcriptomic changes in the network based on the expression and co-expression levels. Our results showed that LRRK2 interactors present both similar but also different alterations in expression levels and co-expression behaviours in the sPD and LRRK2-PD cases. The similar changes result in decreased connectivity within a topological cluster of the LRRK2 PPI network associated with ribosomal functions and DNA/RNA metabolism in both the sPD and LRRK2-PD scenario; while the connectivity within the autophagy/mitophagy/neurotransmitter-transport related cluster was increased exclusively in the LRRK2-PD condition as compared to the healthy controls. These results suggest that, albeit being classified as the same disease based on clinical features, LRRK2-PD and sPD show some significant differences from a molecular perspective.

neuroscience↗

bioRxiv2023

CD36-Pyruvate Kinase M2 Signaling Promotes Macrophage Phagocytosis Through Mitochondrial Reactive Oxygen Species

Macrophage efferocytosis, the process by which phagocytes engulf and remove apoptotic cells (ACs), plays a critical role in maintaining tissue homeostasis. Efficient efferocytosis prevents secondary necrosis, mitigates chronic inflammation, and impedes atherosclerosis progression. However, the regulatory mechanisms of efferocytosis under atherogenic conditions remain poorly understood. We previously demonstrated that oxidized LDL (oxLDL), an atherogenic lipoprotein, induces mitochondrial reactive oxygen species (mtROS) in macrophages via CD36. In this study, we demonstrate that macrophage mtROS facilitate continual efferocytosis through a positive feedback mechanism. However, oxLDL disrupts continual efferocytosis by dysregulating the internalization of ACs. This disruption is mediated by an overproduction of mtROS. Mechanistically, oxLDL/CD36 signaling promotes the translocation of cytosolic PKM2 to mitochondria, facilitated by the chaperone GRP75. Mitochondrial PKM2 then binds to Complex III of the electron transport chain, inducing mtROS production. This study elucidates a novel regulatory mechanism of efferocytosis in atherosclerosis, providing potential therapeutic targets for intervention. SUMMARYMacrophages clear apoptotic cells through a process called efferocytosis, which involves mitochondrial ROS. However, the atherogenic oxidized LDL overstimulates mitochondrial ROS via the CD36-PKM2 pathway, disrupting continual efferocytosis. This finding elucidates a novel molecular mechanism that explains defects in efferocytosis, driving atherosclerosis progression.

immunology↗

bioRxiv2023

Detecting signals of critical transition in inclusive teaching in biology education: A computational text analysis of CourseSource

We examine every Inclusive Teaching section in articles published by the journal CourseSource - undergraduate biology teaching materials and related essays - from 2014 to 2022 to understand the evolution of inclusive teaching ideas as expressed through language. We find a rapid shift in attention to inclusive teaching occurs between 2018 and 2019, marked by an increase in section length, increased use of inclusive teaching keywords, and an increase in complexity of ideas in the semantic network. This critical transition occurs before many of the recent events in 2020 which have renewed conversation on equity in education. Some effect is associated with Writing Workshop Faculty Mentoring Networks, which provide participants with authoring resources and support. However, this alone is not enough to explain the observed shift, suggesting that many other structures, conversations, and investments were already providing the fertile ground for educational equity in biology education.

scientific communication and education↗

bioRxiv2023

Unanticipated interacting features of human gut-associated lymphoid tissues link microbiota, intestinal immunity and autoimmunity

Gut-associated lymphoid tissue (GALT) is organised lymphoid tissue that is chronically activated by the intestinal microbiota. It generates the IgA response that is critical for intestinal homeostasis. By iterative application of multiplexed technologies, we identify enrichment of double-negative 2 (DN2:CD27-IgD-CD21loCD11chi) B cells in GALT, where they comprise the majority of intraepithelial and subepithelial B cells. We show that DN2 B cells in GALT interact with DC in the sub-epithelial dome that express DNASE1L3 and microbicides. Unlike in mice, DNASE1L3 in humans does not associate with apoptotic debris, but is located between sampled bacteria and host tissue where it is co-expressed with C1Q, consistent with management of bacterial debris. Thus we demonstrate that DN2 B cells that are otherwise associated with lupus nephritis, and DNASE1L3 and C1q that are lupus autoantigens, are microbiota-associated, interacting components of normal intestinal immunity.

immunology↗

bioRxiv2023

Metabolites with benzene ring from sugarcane leaf play important role in plant-Spodoptera frugiperda interaction

Secondary metabolism plays important role in plant growth and development, however, the relationship between secondary metabolism and adaptive plant-insect communication is largely unknown. The present study used sugarcane line highly susceptible to Spodoptera frugiperda and sister line with medium resistance to analyze the role of plant non-volatile organic compounds (NOCs) and volatile organic compounds (VOCs) in sugarcane-S. frugiperda interaction. A total of 46 plant NOCs and 15 plant VOCs significantly different between resistant and susceptible lines and were continuously up-regulated and down-regulated at different time points before/after S. frugiperda treatment were screened. Phenolic acids containing benzene ring accounted for the largest proportion of differential NOCs. Levels of 66.7% of these phenolic acids were higher in susceptible line. Feeding supplemented with NOCs showed that phenoxyacetic acid (phenolic acid) and 4-methoxybenzaldehyde (aromatic phenolic acid) both increased the male-to-female ratio of S. frugiperda. Aromatics containing benzene ring, accounted for the largest of differential VOCs in susceptible line. Two aromatics, p-cymene and benzene and 1-ethenyl-4-methoxy-, with higher level in susceptible line, were attractive to S. frugiperda. Terpenoids, aldehyde, and esters accounted for most of higher-in-resistant VOCs, with most tested to be repellent to S. frugiperda. Furthermore, transcriptome analysis of S. frugiperda feeding on susceptible and resistant lines combined with feeding assays revealed that tryptophan, as a precursor of aromatic compounds that also contains benzene ring, could promote the growth and development of S. frugiperda in nutritional deficiency condition. These findings together suggested that benzene-ring containing compounds play a critical role in plant-Spodoptera frugiperda interaction.

ecology↗

bioRxiv2023

A novel, N2-fixing cyanobacterium present and active in the global oceans

Marine N2-fixing cyanobacteria, including the unicellular genus Crocosphaera, are considered keystone species in marine food webs. Crocosphaera are globally distributed and provide new sources of nitrogen (N) and carbon (C), which fuel oligotrophic microbial communities and upper trophic levels. Despite their ecosystem importance, only one species, Crocosphaera watsonii, has ever been identified and characterized as widespread in the oligotrophic oceans. Herein, we present a novel species, candidatus Crocosphaera waterburyi (C. waterburyi hereafter), enriched from the North Pacific Ocean, active in situ, and globally distributed in environmental datasets. C. waterburyi is morphologically, phylogenetically, and physiologically distinct from C. watsonii; therefore, description of this novel species provides a new window into previously uncharacterized diversity and ecology of unicellular N2-fixing cyanobacterial taxa and further highlights their importance in the global N cycle.

genomics↗

bioRxiv2023

Identification of a subpopulation of highly adherent endothelial cells for seeding synthetic vascular grafts

ObjectiveThere is an unmet clinical need for a bypass graft that can be used as an alternative to an autologous vessel graft for the treatment of severe coronary artery disease. Small-diameter (<6mm) synthetic vascular grafts are not suitable because of unacceptable patency rates. This mainly occurs without an endothelial cell (EC) monolayer to prevent platelet activation, thrombosis, and intimal hyperplasia. While numerous studies have explored methods to improve EC adhesion to biomaterials, there are still no reliable methods to endothelialize small-diameter grafts, as most seeded ECs are lost due to exposure to fluid shear stress (SS) after implantation. The goal of this work is to determine if EC loss is a random process or if it is possible to predict which cells are more likely to remain adherent. Approach and ResultsIn initial studies, we sorted ECs using fluid SS and identified a subpopulation of ECs that are more likely to resist detachment. We use RNA-sequencing (RNA-seq) to examine gene expression of adherent ECs compared to the whole population to identify targets for improving adhesion. Fibronectin leucine rich transmembrane protein 2 (FLRT2), which encodes protein FLRT2, emerged as a candidate due to its downregulation in the adherent ECs and known role in cell adhesion. Using fluorescence activated cell sorting (FACS), we sorted ECs based on FLRT2 expression levels and demonstrated that ECs expressing low levels of FLRT2 exhibit greater retention under fluid SS in vitro. ConclusionFor the first time, we show EC detachment is not an entirely random process and we predicted which ECs were more likely to remain adherent on a vascular graft upon exposure to fluid SS. This provides validation for the concept that we can seed a small-diameter vascular graft only with highly adherent ECs to maintain a stable endothelium and improve graft patency rates. Non-standard Abbreviations and Acronymsendothelial cell (EC), shear stress (SS), fibronectin leucine rich transmembrane protein 2 (FLRT2), tissue engineered vascular graft (TEVG), fluorescence activated cell sorting (FACS)

bioengineering↗

bioRxiv2023

The translation of a short open reading frame product within the human TUBA1B gene regulates cancer cell proliferation by importin-β

Understanding cancer biology is crucial for improving treatment strategies. This study identified TUBA1B-sORF1, a short open reading frame product alternatively translated from the human -tubulin gene (TUBA1B), which has a completely different amino acid sequence from the -tubulin 1B chain. TUBA1B-sORF1 is highly expressed in cancer cell lines and gastric carcinoma. Both methionine-initiated canonical and leucine-initiated noncanonical translations of TUBA1B-sORF1 coexist in cancer cells, and there is a transition between sORF1 and -tubulin translations, evidenced by the TUBA1B-sORF1/-tubulinlow/- subpopulation. Knocking down TUBA1B-sORF1 reduces cancer cell proliferation and tumorigenicity. TUBA1B-sORF1 facilitates protein nuclear translocation, leading to the upregulation of proliferation-promoting genes and downregulation of proliferation-inhibiting genes. Specifically, it forms a complex with importin {beta} and {beta}-catenin, promoting {beta}-catenin nuclear translocation and target gene transcription. These findings reveal that TUBA1B is a polycistronic gene translating at least two entirely different proteins: -tubulin and TUBA1B-sORF1. The variable translation between them may regulate tumorigenesis, making TUBA1B-sORF1 a promising therapeutic target and diagnostic biomarker for cancer treatment.

cancer biology↗

bioRxiv2023

Proportionality-based association metrics in count compositional data

MotivationCompositional data comprise vectors that describe the constituent parts of a whole. Data arising from various -omics platforms such as 16S and RNA-sequencing are compositional in nature. However, correlations between features on raw counts have no meaningful interpretation. Metrics of proportionality were formulated to address this problem. However, there is an inherent bias that arises when calculating these metrics empirically on count-based measures due to variability in read depths. ResultsWe quantify the bias introduced by empirically calculating proportionality-based association metrics in count data. Additionally, we propose a means of estimating these metrics within a logit-normal multinomial model in pursuit of more accurate estimates. The model-based estimates are shown to outperform empirical estimates in simulated data, and are additionally applied to a mouse embryonic stem-cell single-cell sequencing dataset as well as a pediatric-onset multiple sclerosis metagenomic dataset. Availability and ImplementationAn R package is available at https://CRAN.R-project.org/package=countprop. Supplementary informationSupplementary data are available at Bioinformatics online.

bioinformatics↗

bioRxiv2023

The longitudinal single-cell panorama of cynomolgus monkey ovary throughout lifespan revealed a conserved ovarian clock between primates

Ovarian function is critical for female fertility and impacts reproductive longevity. It is of great importance to accurately predict the aging process within the ovary for fertility assessment and disease diagnosis. However, cell metrics for evaluating the ovarian aging rate are still in urgent need, and molecular insights into ovarian development and dysfunction during the primate life course are also limited. Here, we reported large-scale ovarian cell atlas of consecutive development of cynomolgus monkeys across 22 years with 20 time points, covering the foetal, newborn, prepubertal, pubertal, adult, perimenopausal and menopausal stages. We characterized and validated distinct molecular signatures of each cluster of cells within primate ovaries, and uncovered a previously undocumented RHOXF1-positive oocyte type during primordial follicle assembly in primates. Furthermore, the constitution and developmental trajectories of primate germ cells, granulosa cells and stromal / theca cells were also elucidated, and their precursors were identified. More importantly, dynamics of cellular compositions were unravelled through the ovarian development, featured by granulosa, epithelial, stromal, and immune cells that showed strong temporal heterogeneity spanning lifetime, whilst referred to the key function during the corresponding stages. Based on the correlations of each cell type with age and stage-specific molecular dynamics, we further constructed a transcriptomic ovarian clock which could perceive an effective biological age prediction of the ovary and further applied to humans. The findings reveal granulosa, epithelial, and stromal cells as the highest performance predictors of ovarian biological age, while highlighting the crucial role of AGE-RAGE and Relaxin signaling pathways in regulating ovarian aging. Our work not only provide valuable resource for obtaining insights into the development, aging and dysfunction of key organs, but also establish a transcriptomic clock to predict biological ovarian aging thus to be potential clinical implementation in future.

developmental biology↗

bioRxiv2023

Small molecule nitroalkenes inhibit RAD51-mediated homologous recombination and amplify triple-negative breast cancer cell killing by DNA-directed therapies.

Nitro fatty acids (NO2-FAs) are endogenously generated lipid signaling mediators from metabolic and inflammatory reactions between conjugated diene fatty acids and nitric oxide or nitrite-derived reactive species. NO2-FAs undergo reversible Michael addition with hyperreactive protein cysteine thiolates to induce posttranslational protein modifications that can impact protein function. Herein, we report a novel mechanism of action of natural and non-natural nitroalkenes structurally similar to (E) 10-nitro-octadec-9-enoic acid (CP-6), recently de-risked by preclinical Investigational New Drug-enabling studies and Phase 1 and Phase 2 clinical trials and found to induce DNA damage in a TNBC xenograft by inhibiting homologous-recombination (HR)-mediated repair of DNA double-strand breaks (DSB). CP-6 specifically targets Cys319, essential in RAD51-controlled HR-mediated DNA DSB repair in cells. A nitroalkene library screen identified two structurally different nitroalkenes, a non-natural fatty acid [(E) 8-nitro- nonadec-7-enoic acid (CP-8)] and a dicarboxylate ester [dimethyl (E)nitro-oct-4-enedioate (CP- 23)] superior to CP-6 in TNBC cells killing, synergism with three different inhibitors of the poly ADP-ribose polymerase (PARP) and {gamma}-IR. CP-8 and CP-23 effectively inhibited {gamma}-IR-induced RAD51 foci formation and HR in a GFP-reported assay but did not affect benign human epithelial cells or cell cycle phases. In vivo, CP-8 and CP-23s efficacies diverged as only CP-8 showed promising anticancer activities alone and combined with the PARP inhibitor talazoparib in an HR-proficient TNBC mouse model. As preliminary preclinical toxicology analysis also suggests CP-8 as safe, our data endorse CP-8 as a novel anticancer molecule for treating cancers sensitive to homologous recombination-mediated DNA repair inhibitors. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=172 SRC="FIGDIR/small/552990v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@1dcec56org.highwire.dtl.DTLVardef@1202a09org.highwire.dtl.DTLVardef@a7e7b6org.highwire.dtl.DTLVardef@15d8925_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

bioRxiv2023

YiNet: An Integrated Traditional Chinese and Western Medicine Platform for Viral Infectious Diseases

Viral infectious diseases (VIDs) impose a heavy burden on global public health. Traditional Chinese medicine (TCM) has previously and is currently contributing to the prevention and treatment of infectious diseases. Omics and information technology enable the precise identification of virus characteristics, virus-host interactions and TCM mechanisms. In this study, we constructed the YiNet platform to better integrate the novel techniques and historical experience of TCM in infectious diseases. YiNet comprises three modules: knowledge base, database and toolkit. The YiNet knowledge base involves 43 VIDs, thereby systematically integrating the knowledge regarding viruses, host symptoms and TCM and Western medicine (commonly used chemical drugs, 6,899 herbs and 2,481 formulas). The YiNet database module includes multiple databases, comprising 57,340 genome sequences of 45,791 viral strains and 5,726 multi-omics datasets such as RNA-seq, ChIP-seq and ATAC-seq from different tissues and cell models. It also integrates 1,105 real-world TCM clinical cases. We adopted visual analysis tool to investigate pathogen-host-herb relationships. To explore pharmacological mechanisms for the core herbs, we added formula data mining and network pharmacology analysis pipelines and visualisation tools. YiNet can facilitate the mechanistic study of TCM and drug development for VIDs. The YiNet platform is publicly available at http://yinet.gene.ac/.

bioinformatics↗