Biology subjects

Wei, Q.

Publications and source records attributed to Wei, Q..

At least 55 records · Page 3Linked to original sources

bioRxiv2023

Skin permeable polymer for noninvasive transdermal insulin delivery

Subcutaneous injection of insulin is the current standard medication for many diabetic patients. Convenient and painless noninvasive transdermal insulin delivery has long been pursued but yet succeeded due to no such technologies for large biomacromolecules. We find a tertiary amine oxide-based polyzwitterion, OPDMA, that can efficiently penetrate both the stratum corneum (SC) and viable epidermis into circulation. So its conjugate with insulin, OPDMA-I, applied on the skin can exhibit hypoglycemic effects as efficiently as subcutaneously injected insulin in type-1 diabetic mice and minipigs. The unique pH-dependent cationic-to-zwitterionic transition of OPDMA in the characteristic acidic-to-neutral pH gradient from the skin surface to deep SC enables fast transdermal delivery of OPDMA and its conjugate. On the skin, OPDMA binds to carboxylic acids in the acidic sebum layer, enriching OPDMA-I on the SC. As pH increases in deeper SC layers, binding between OPDMA-I and the skin weakens gradually, allowing for diffusion through inter-corneocyte gaps and penetration into viable epidermis and finally entering the systemic circulation via dermal lymphatic vessels. This process does not alter SC microstructures or cause any physiological changes in the skin. This study represents a groundbreaking example of noninvasive transdermal protein delivery.

bioengineering↗

bioRxiv2023

Self-supervised deep learning of gene-gene interactions for improved gene expression recovery

Single-cell RNA sequencing (scRNA-seq) has emerged as a powerful tool to gain biological insights at the cellular level. However, due to technical limitations of the existing sequencing technologies, low gene expression values are often omitted, leading to inaccurate gene counts. The available methods, including state-of-the-art deep learning techniques, are incapable of imputing the gene expressions reliably because of the lack of a mechanism to explicitly consider the underlying biological knowledge of the system. Here we tackle the problem in two steps to exploit the gene-gene interactions of the system: (i) we reposition the genes in such a way that their spatial configuration reflects their interactive relationships; and (ii) we use a self-supervised 2D convolutional neural network to extract the contextual features of the interactions from the spatially configured genes and impute the omitted values. Extensive experiments with both simulated and experimental scRNA-seq datasets are carried out to demonstrate the superior performance of the proposed strategy against the existing imputation methods.

genomics↗

bioRxiv2023

Morphine Re-arranges Chromatin Spatial Architecture of Primate Cortical Neurons

The expression of linear DNA sequences is precisely regulated by the three-dimensional (3D) architecture of chromatin. Morphine-induced aberrant gene networks of neurons have been extensively investigated; however, how morphine impacts the 3D genomic architecture of neuorns is still unknown. Here, we applied digestion-ligation-only high-throughput chromosome conformation capture (DLO Hi-C) technology to investigate the affection of morphine on 3D chromatin architecture of primate cortical neurons. After receiving continuous morphine administration for 90 days on rhesus monkeys, we discovered that morphine re-arranged chromosome territories, with a total of 391 segmented compartments being switched. Morphine altered over half of the detected topologically associated domains (TADs), most of which exhibited a variety of shifts, followed by separating and fusing types. Analysis of the looping events at kilobase-scale resolution revealed that morphine increased not only the number but also the length of differential loops. Moreover, all identified differentially expressed genes (DEGs) from the RNA sequencing (RNA-seq) were mapped to the specific TAD boundaries or differential loops, and were further validated to be significantly changed. Collectively, an altered 3D genomic architecture of cortical neurons may regulate the gene networks associated-morphine effects. Our finding provides critical hubs connecting chromosome spatial organization and gene networks associated with the morphine effects in humans.

bioinformatics↗

bioRxiv2023

Interrogating the function of bicistronic translational control elements to improve consistency of gene expression

Context independent gene expression is required for genetic circuits to maintain consistent and predicable behavior. Previous efforts to develop context independent translation have leveraged the helicase activity of translating ribosomes via bicistronic design translational control elements (BCDs) located within an efficiently translated leader peptide. We have developed a series of bicistronic translational control elements with strengths that span several orders of magnitude, maintain consistent expression levels across diverse sequence contexts, and are agnostic to common ligation sequences used in modular cloning systems. We have used this series of BCDs to investigate several features of this design, including the spacing of the start and stop codons, the nucleotide identity upstream of the start codon, and factors affecting translation of the leader peptide. To demonstrate the flexibility of this architecture and their value as a generic modular expression control cassette for synthetic biology, we have developed a set of robust BCDs for use in several Rhodococcus species.

synthetic biology↗

bioRxiv2022

A library of promoter-gfp fusion reporters for studying systemic expression pattern of cyclic-di-GMP metabolism-related genes in Pseudomonas aeruginosa

The opportunistic pathogen Pseudomonas aeruginosa is an environmental microorganism, which is notorious for its resistance or tolerance to antibiotics due to the formation of biofilms. Cyclic diguanosine monophosphate (c-di-GMP) is a bacterial second messenger that plays critical roles in biofilm formation. P. aeruginosa contains 41 genes that encode enzymes to participate in the metabolism of c-di-GMP (biosynthesis or degradation), yet it lacks tools to investigate the systemic expression pattern of those genes. Here, we constructed a promoter-gfp transcriptional fusion reporters library that consists of 41 reporter plasmids. Each plasmid contains a promoter of corresponding c-di-GMP metabolism-related (CMR) genes from P. aeruginosa PAO1 strain, thus each promoter-Gfp fusion reporter can be used to detect the promotor activity as well as the transcription of corresponding gene. The promoters activity was tested in P. aeruginosa and Escherichia coli respectively. Among the 41 genes, the promoter of 26 genes showed activity in both P. aeruginosa and E. coli. The library was applied to determine the influence of different temperatures, growth media, and sub-inhibitory concentrations of antibiotics on transcriptional profile of the 41 CMR genes in P. aeruginosa. The results showed different growth conditions did impact different genes transcription, while the promoter activity of a few genes kept at the same level under several different growth conditions. In summary, we provided a promoter-gfp fusion reporters library for systemic monitoring or study of the regulation of CMR genes in P. aeruginosa and the functional promoters can also be used as a bio-brick for synthetic biology studies. ImportanceThe opportunistic pathogen P. aeruginosa can cause acute and chronic infections in humans and it is one of main pathogens in nosocomial infections. Biofilm formation is one of most important causes for P. aeruginosa to persist in hosts and evade immune and antibiotic attacks. c-di-GMP is an important second messenger to control biofilm formation. In P. aeruginosa, there are 41 genes that are predicted to participate in the making and breaking this dinucleotide. A major missing information in this field is the systemic expression profile of those genes in response to changing environment. Toward this goal, we constructed a promoter-gfp transcriptional fusion reporters library that consists of 41 reporter plasmids, each of which contains a promoter of corresponding c-di-GMP metabolism-related genes in P. aeruginosa. This library provides a helpful tool to understand the complex regulation network related to c-di-GMP and to discover potential therapeutic targets.

microbiology↗

bioRxiv2022

Integrating inflammatory biomarker analysis and artificial intelligence-enabled image-based profiling to identify drug targets for intestinal fibrosis

Intestinal fibrosis is a common complication of several enteropathies with inflammatory bowel disease being the major cause. The progression of intestinal fibrosis may lead to intestinal stenosis and obstruction. Even with an increased understanding of tissue fibrogenesis, there are no approved treatments for intestinal fibrosis. Historically, drug discovery for diseases like intestinal fibrosis has been impeded by a lack of screenable cellular phenotypes. Here we applied Cell Painting, a scalable image-based morphology assay, augmented with machine learning algorithms to identify small molecules that were able to morphologically reverse the activated fibrotic phenotype of intestinal myofibroblasts under pro-fibrotic TNF stimulus. In combination with measuring CXCL10, a common pro-inflammatory cytokine in intestinal fibrosis, we carried out a high-throughput small molecule chemogenomics screen of approximately 5000 compounds with known targets or mechanisms, which have achieved clinical stage or approval by the FDA. Through the use of two divergent analytical methods, we identified several compounds and target classes that are potentially able to treat intestinal fibrosis. The phenotypic screening platform described here represents significant improvements in identifying a wide range of drug targets over conventional methods by integrating morphological analyses and artificial intelligence using pathologically-relevant cells and disease-relevant stimuli.

pharmacology and toxicology↗

bioRxiv2022

High emotional reactivity is associated with activation of a molecularly distinct hippocampal-amygdala circuit modulated by the glucocorticoid receptor

Emotions are characterized not only by their valence but also by whether they are stable or labile. Yet, we do not understand the molecular or circuit mechanisms that control the dynamic nature of emotionality. We have shown that glucocorticoid receptor overexpression in the forebrain (GRov) leads to a highly reactive mouse with increased anxiety behavior coupled with greater swings in emotional responses. This phenotype is established early in development and persists into adulthood. However, the neural circuitry mediating this lifelong emotional lability remains unknown. In the present study, optogenetic stimulation in ventral dentate gyrus (vDG) of GRov mice led to a greater range and a prolonged duration of anxiety behavior. cFos expression showed that the amplified behavioral response to vDG activation in GRov mice is coupled to increased neuronal activity in specific brain regions. Relative to wild type mice, GRov mice displayed glutamatergic/GABAergic activation imbalance in ventral CA1 (vCA1) and selectively increased glutamatergic activation in the basal posterior amygdaloid complex. Fluorescence in situ hybridization chain reaction studies showed that forebrain GR overexpression led to increased activation of molecularly distinct subpopulations of neurons within the hippocampus and the posterior basolateral amygdala (pBLA). Increased cFos labeling was observed in the Calbindin 1 (Calbn1+) glutamatergic neurons in vCA1 and in the DARPP-32/Ppp1r1b+ glutamatergic neurons in pBLA. We propose that a molecularly distinct hippocampal-amygdala circuit is shaped by stress early in life and tunes the dynamics of emotional responses.

neuroscience↗

bioRxiv2022

Social Regulation of Egg Size Plasticity in the Honey Bee is Mediated by Cytoskeleton Organizer Rho1

Egg size plasticity represents an adaptive reproductive strategy in numerous organisms, including the honey bee, Apis mellifera. However, the proximate causation of this plasticity and egg size in general is unknown. We show that honey bee queens predictably and reversibly adjust egg size in response to their colony size and that this plasticity is an active response to the queens perception of colony size instead of a consequence of egg laying rate. The egg size increase involves changes of 290 ovarian proteins, mostly related to increased energy metabolism, protein transport, and cytoskeleton functions. Spatio-temporal expression analysis of the small GTPase Rho1 indicates its central role in egg size regulation, which we confirm by RNAi-mediated gene knock-down and expression analyses. The molecular adjustments that promote maternal investment of honey bee queens in response to their social environment thus reveal a novel mechanism of egg size regulation.

evolutionary biology↗

bioRxiv2022

Machine Learning Classification Reveals Robust Morphometric Biomarker of Glial and Neuronal Arbors

Neurons and glia are the two main cell classes in the nervous systems of most animals. Although functionally distinct, neurons and glia are both characterized by multiple branching arbors stemming from the cell bodies. Glial processes are generally known to form smaller trees than neuronal dendrites. However, the full extent of morphological differences between neurons and glia in multiple species and brain regions has not yet been characterized, nor is it known whether these cells can be reliably distinguished based on geometric features alone. Here, we show that multiple supervised learning algorithms (K-nearest neighbor, random forest, and support vector machine) deployed on a large database of morphological reconstructions can systematically classify neuronal and glial arbors with nearly perfect accuracy and precision. Moreover, we report multiple morphometric properties, both size-related and size-independent, that differ substantially between these cell types. In particular, we newly identify an individual morphometric measurement, Average Branch Euclidean Length (ABEL) that can robustly separate neurons from glia across multiple animal models, a broad diversity of experimental conditions, and anatomical areas, with the notable exception of the cerebellum. We discuss the practical utility and physiological interpretation of this discovery.

bioengineering↗

bioRxiv2022

Protein Kinase C Delta Regulates Mononuclear Phagocytes and Hinders Response to Immunotherapy in Cancer

Checkpoint immunotherapy unleashes T cell antitumor potential which has revolutionized cancer treatment showing unprecedented long-term responses. However, most patients do not respond to immunotherapy which often correlates with a dysfunctional or immunosuppressive myeloid compartment. The mononuclear phagocyte system (MPS) is a sub-class of myeloid cells comprising monocytes, macrophages and dendritic cells which plays a crucial role in tissue homeostasis. However, accumulating evidence suggests that mononuclear phagocytes contribute to all phases of tumorigenesis including orchestrating inflammatory events during de novo carcinogenesis, contribution to the progression of established tumors and promotion of resistance to checkpoint blockade. Thus, targeting the MPS could be an effective strategy to enhance checkpoint blockade efficacy and promote control of tumors. Here, we found that protein kinase C delta (PKC{delta}), a serine/threonine kinase, is abundantly expressed by mononuclear phagocytes in several human and mouse tumors. PKC{delta}-/- mice were more resistant to growth of various cancers compared to wild-type mice and were more responsive to anti-PD-1 immunotherapy. Furthermore, we found that tumors from PKC{delta}-/- mice harbor a Th-1-skewed immune landscape including increased antigen cross-presentation and T cell activation. Depletion of mononuclear phagocytes in vivo altered tumor growth in wild-type mice, but not in PKC{delta}-/- mice. In addition, coinjection of PKC{delta}-/--deficient M2-like macrophages with cancer cells into wild-type mice markedly delayed tumor growth and significantly increased intratumoral T cell activation compared to wild-type M2-like macrophages coinjected with cancer cells. Finally, intrinsic loss of PKC{delta}-/- functionally reprogrammed macrophages and dendritic cells by promoting their antigen presenting and cross-presenting capacity and triggered type I and type II interferon signaling. Thus, PKC{delta} might be targeted to reprogram mononuclear phagocytes and augment checkpoint blockade efficacy.

immunology↗

bioRxiv2022

Integrated analysis reveals FOXA1 and Ku70/Ku80 as direct targets of ivermectin in prostate cancer

Ivermectin is a widely used antiparasitic drug and shows promising anticancer activity in various cancer types. Although multiple signaling pathways modulated by ivermectin have been identified, few studies have focused on the exact target of ivermectin. Herein, we report the pharmacological effects and direct targets of ivermectin in prostate cancer (PCa). Ivermectin caused G0/G1 arrest, induced cell apoptosis, DNA damage, and decreased androgen receptor (AR) signaling in PCa cells. Using integrated omics profiling, including RNA-seq and thermal proteome profiling, we found that the forkhead box protein A1 (FOXA1) and non-homologous end joining (NHEJ) repair executer Ku70/Ku80 were the direct targets of ivermectin. The binding of ivermectin and FOXA1 reduced the chromatin accessibility of AR and the G0/G1 cell cycle regulator E2F1, leading to cell proliferation inhibition. The binding of ivermectin and Ku70/Ku80 impaired the NHEJ repair ability. Cooperating with the downregulation of homologous recombination repair after AR inhibition, ivermectin triggered synthetic lethality. Our findings demonstrate the anticancer effect of ivermectin in prostate cancer, indicating that its use may be a new therapeutic approach for PCa.

cancer biology↗

bioRxiv2022

Forebrain glucocorticoid receptor overexpression alters behavioral encoding of hippocampal CA1 pyramidal cells in mice

Stress hormone signaling via the glucocorticoid receptor (GR) modulates vulnerability to stress-related disorders, but whether GR influences how the brain encodes contextual experience is unknown. Mice with lifelong GR overexpression in forebrain glutamatergic neurons (GRov) show increased sensitivity to environmental stimuli. This phenotype is developmentally programmed and associated with profound changes in hippocampal gene expression. We hypothesized that GR overexpression influences hippocampal encoding of experiences. To test our hypothesis, we performed in vivo microendoscopic calcium imaging of 1359 dorsal CA1 pyramidal cells in freely behaving male and female WT and GRov mice during exploration of a novel open field. We compared calcium amplitude and event rate as well as sensitivity to center location and mobility between genotypes. GRov neurons exhibited higher average calcium activity than WT neurons in the novel open field. While most neurons showed sensitivity to center location and/or mobility, GRov neurons were more likely to be sensitive to center location and less likely to be sensitive to mobility, as compared to WT neurons. More than one-third of behavior-selective GRov neurons were uniquely sensitive to location without mobility sensitivity; these uniquely center-sensitive neurons were rare in WT. We conclude that dorsal CA1 pyramidal cells in GRov mice show increased activity in a novel environment and preferentially encode emotionally salient behavior. This heightened sensitivity to a novel environment and preferential encoding of emotionally salient elements of experience could underlie differential stress vulnerability in humans with increased glucocorticoid sensitivity. Significance Statement (120 words maximum)Endogenous stress hormones, glucocorticoids, are known to alter vulnerability to stress-related disorders. Here, we find that increased sensitivity to glucocorticoid via lifelong overexpression of glucocorticoid receptor in forebrain neurons (GRov) alters the encoding of environmental experiences in the hippocampus. GRov mice showed increased activity of dorsal CA1 hippocampal pyramidal cells during exploration of a novel environment and more sensitivity to emotionally relevant behaviors. These changes in how hippocampal neurons encode environmental experiences could underlie the differences in stress vulnerability in humans with genetic and epigenetic differences in glucocorticoid receptor signaling.

neuroscience↗

bioRxiv2022

SpotLink enables sensitive and precise identification of site non-specific cross-links at the proteome scale

We developed SpotLink software for identifying site non-specific cross-links at the proteome scale. Contributed by the dual pointer dynamic pruning (DPDP) algorithm and the quality control of cross-linking sites, SpotLink identified more than 3000 cross-links from human proteome database with rich site information in a few days. We demonstrated that SpotLink outperformed other approaches in terms of sensitivity and precision on a simulated dataset and a protein complexes dataset with known structures. Additionally, we discovered some valuable protein-protein interaction (PPI) information contained in the protein complexes dataset and HeLa dataset, indicating the unique identification advantages of site non-specific cross-linking. The excellent performance of SpotLink will increase the usage of site non-specific cross-linking in the near future. SpotLink is publicly available on GitHub [https://github.com/DICP1810/SpotLink].

bioinformatics↗

bioRxiv2021

Whole-genome sequencing of Chinese native goat offers biological insights into cashmere fiber formation

Cashmere evolved naturally in the goat, and almost all breeds of goat can produce more or less cashmere fibers. However, the genetic alterations underlying cashmere trait selection are still unclear.We sequenced 120 Chinese native goat including two cashmere goat breeds (Ujumain, Chaidamu) and six ordinary goat breeds (Jining Gray, Matou, Guizhou Black, Jintang Black, Yunnan Black Bone, Chengdu Brown). The genome-wide selective sweep of cashmere goat and ordinary goat revealed a novel set of candidate genes as well as pathways, such as Nuclear factor kappa-B and Wnt Signaling pathways. Of them, the LHX2 gene regulating hair follicle development, was evident from the strongest selection signal when comparing the Uhumqin cashmere goat and ordinary goat. Interestingly, we identified a 582bp deletion at 367 kb upstream of LHX2 with higher frequency in cashmere goats and their ancient relatives. This mutation probably rises along the breeding procedures, and is putatively responsible for cashmere production and diameter, as revealed by association studies. Luciferase assay shows that the deletion, which acts as an insulator, restrains the expression of LHX2 by interfering its upstream enhancers.Our study discovers a novel insulator of the LHX2 involved in regulating cashmere production and diameter, which would be beneficial to understanding hair follicle development and regeneration. Our findings also provide new insights into the genetic formation of cashmere, and facilitate subsequent molecular breeding for cashmere goat improvement.

genomics↗

bioRxiv2021

Integration of multidimensional splicing data and GWAS summary statistics for risk gene discovery

A common strategy for the functional interpretation of genome-wide association study (GWAS) findings has been the integrative analysis of GWAS and expression data. Using this strategy, many association methods (e.g., PrediXcan and FUSION) have been successful in identifying trait-associated genes via mediating effects on RNA expression. However, these approaches often ignore the effects of splicing, which carries as much disease risk as expression. Compared to expression data, one challenge to detect associations using splicing data is the large multiple testing burden due to multidimensional splicing events within genes. Here, we introduce a multidimensional splicing gene (MSG) approach, which consists of two stages: 1) we use sparse canonical correlation analysis (sCCA) to construct latent canonical vectors (CVs) by identifying sparse linear combinations of genetic variants and splicing events that are maximally correlated with each other; and 2) we test for the association between the genetically regulated splicing CVs and the trait of interest using GWAS summary statistics. Simulations show that MSG has proper type I error control and substantial power gains over existing multidimensional expression analysis methods (i.e., S-MultiXcan, UTMOST, and sCCA+ACAT) under diverse scenarios. When applied to the Genotype-Tissue Expression Project data and GWAS summary statistics of 14 complex human traits, MSG identified on average 83%, 115%, and 223% more significant genes than sCCA+ACAT, S-MultiXcan, and UTMOST, respectively. We highlight MSGs applications to Alzheimers disease, low-density lipoprotein cholesterol, and schizophrenia, and found that the majority of MSG-identified genes would have been missed from expression-based analyses. Our results demonstrate that aggregating splicing data through MSG can improve power in identifying gene-trait associations and help better understand the genetic risk of complex traits. Author summaryWhile genome-wide association studies (GWAS) have successfully mapped thousands of loci associated with complex traits, it remains difficult to identify which genes they regulate and in which biological contexts. This interpretation challenge has motivated the development of computational methods to prioritize causal genes at GWAS loci. Most available methods have focused on linking risk variants with differential gene expression. However, genetic control of splicing and expression are comparable in their complex trait risk, and few studies have focused on identifying causal genes using splicing information. To study splicing mediated effects, one important statistical challenge is the large multiple testing burden generated from multidimensional splicing events. In this study, we develop a new approach, MSG, to test the mediating role of splicing variation on complex traits. We integrate multidimensional splicing data using sparse canonocial correlation analysis and then combine evidence for splicing-trait associations across features using a joint test. We show this approach has higher power to identify causal genes using splicing data than current state-of-art methods designed to model multidimensional expression data. We illustrate the benefits of our approach through extensive simulations and applications to real data sets of 14 complex traits.

genetics↗

bioRxiv2021

Robust maintenance of cell surface tension in mitosis by RhoA-driven myosin II mechanoresponse

Non-muscle myosin II (NMII) is a force-generating mechanosensitive enzyme that responds to mechanical forces exerted on cells. Mechanoresponse of NMIIs confers mechanical adaptability to cells growing and dividing in a physically complex microenvironment. In response to mechanical forces, NMIIs mechanoaccumulate at the cell cortex with applied stress. Much less is known about how NMII mechanoaccumulation is mechanistically regulated. In this study, we subject cells in mitosis to compressive forces and show that mitotic cells promote active RhoA mechanoaccumulation, and via ROCK signaling, activate and stabilize NMIIB at the cell cortex. In line with RhoA in activating the myosin motor activity, we further show that the motor activity driving actin filament translocation, but not just the actin-binding function of NMIIB plays a dominant regulatory role in NMIIB mechanoaccumulation. Thus, the motor activity coordinates structural movement and nucleotide state changes to fine-tune actin-binding affinity optimal for NMIIs to generate and respond to forces.

cell biology↗

bioRxiv2021

Lupus Gut Microbiota Transplants Cause Autoimmunity and Inflammation

BackgroundThe etiology of systemic lupus erythematosus (SLE) is multifactorial. Recently, growing evidence suggests that the microbiota plays a role in SLE, yet whether gut microbiota participates in the development of SLE remains largely unknown. To investigate this issue, we carried out 16s rDNA sequencing analyses in a cohort of 18 female un-treated active SLE patients and 7 female healthy controls, and performed fecal microbiota transplantation from patients and healthy controls to germ-free mice. ResultsCompared to the healthy controls, we found no significant different microbial diversity but some significantly different species in SLE patients including Turicibacter genus and other 5 species. Fecal transfer from SLE patients to germ free (GF) C57BL/6 mice caused GF mice to develop a series of lupus-like phenotyptic features, which including an increased serum autoimmune antibodies, and imbalanced cytokines, altered distribution of immune cells in mucosal and peripheral immune response, and upregulated expression of genes related to SLE in recipient mice that received SLE fecal microbiota transplantation (FMT). Moreover, the metabolism of histidine was significantly altered in GF mice treated with SLE patient feces, as compared to those which received healthy fecal transplants. ConclusionsOverall, our results describe a causal role of aberrant gut microbiota in contributing to the pathogenesis of SLE. The interplay of gut microbial and histidine metabolism may be one of the mechanisms intertwined with autoimmune activation in SLE.

immunology↗

bioRxiv2021

Whole genome sequencing revealed genetic diversity and selection of Guangxi indigenous chickens

Guangxi chickens play an important role in promoting the high-quality development of the broiler industry in China, but their value and potential are yet to be discovered. To determine the genetic diversity and population structure of Guangxi indigenous chicken, we analyzed the whole genomes of 185 chicken from 8 phenotypically and geographically representative Guangxi chicken breeds, together with 12 RJFt, 12 BRA and 12 WL genomes available from previous studies. Calculation of heterozygosity (Hp), nucleotide diversity ({pi}), and LD level indicated that Guangxi populations were characterized by higher genetic diversity and lower differentiation than RJFt and commercial breeds except HGFC. Population structure analysis also confirmed the introgression from commercial broiler breeds. Each population clustered together while the overall differentiation was small, MA has the richest genetic diversity among all varieties. Selective sweep analysis revealed BCO2, EDN3 and other candidate genes have received strong selection in local breeds, these also provided novel breeding visual and data basis for future breeding.

genetics↗