Biology subjects

Xiao, X.

Publications and source records attributed to Xiao, X..

At least 127 records · Page 7Linked to original sources

bioRxiv2021

IMCellXMBD: A statistical approach for robust cell identification and quantification from imaging mass cytometry images

Imaging Mass Cytometry (IMC) has become a useful tool in biomedical research due to its capability to measure over 100 markers simultaneously. Unfortunately, some protein channels in IMC images can be very noisy, which may significantly affect the phenotyping results without proper data processing. We developed IMCellXMBD1, a highly effective and generalizable cell identification and quantification method for IMC images. IMCell performs denoising by subtracting an estimated background noise value from pixel values for each individual protein channel, identifies positive cells from negative cells by comparing the distribution between segmented cells and decoy cells, and normalize the protein expression levels of the identified positive cells for downstream data analysis. Experimental results demonstrate that our method significantly improves the reliability of cell phenotyping which is essential for using IMC in biomedical studies.

bioinformatics↗

bioRxiv2021

Broad ultra-potent neutralization of SARS-CoV-2 variants by monoclonal antibodies specific to the tip of RBD

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) continue to wreak havoc across the globe. Higher transmissibility and immunologic resistance of VOCs bring unprecedented challenges to epidemic extinguishment. Here we describe a monoclonal antibody, 2G1, that neutralizes all current VOCs and has surprising tolerance to mutations adjacent to or within its interaction epitope. Cryo-electron microscopy structure showed that 2G1 bound to the tip of receptor binding domain (RBD) of spike protein with small contact interface but strong hydrophobic effect, which resulted in nanomolar to sub-nanomolar affinities to spike proteins. The epitope of 2G1 on RBD partially overlaps with ACE2 interface, which gives 2G1 ability to block interaction between RBD and ACE2. The narrow binding epitope but high affinity bestow outstanding therapeutic efficacy upon 2G1 that neutralized VOCs with sub-nanomolar IC50 in vitro. In SARS-CoV-2 and Beta- and Delta-variant-challenged transgenic mice and rhesus macaque models, 2G1 protected animals from clinical illness and eliminated viral burden, without serious impact to animal safety. Mutagenesis experiments suggest that 2G1 could be potentially capable of dealing with emerging SARS-CoV-2 variants in future. This report characterized the therapeutic antibodies specific to the tip of spike against SARS-CoV-2 variants and highlights the potential clinical applications as well as for developing vaccine and cocktail therapy.

cell biology↗

bioRxiv2021

Enterotoxigenic Escherichia coli display a distinct growth phase before entry into stationary phase with shifts in tryptophan- fucose- and putrescine metabolism and degradation of neurotransmitter precursors

Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrhea in children and adults in endemic areas. Gene regulation of ETEC during growth in vitro and in vivo needs to be further evaluated, and here we describe the full transcriptome and metabolome of ETEC during growth from mid-logarithmic growth to stationary phase in rich medium (LB medium). We identified specific genes and pathways subjected to rapid transient alterations in gene expression and metabolite production during the transition between logarithmic to stationary growth. The transient phase during late exponential growth is different from the subsequent induction of stationary phase-induced genes, including stress and survival responses as described earlier. The transient phase was characterized by the repression of genes and metabolites involved in organic substance transport. Genes involved in fucose and putrescine metabolism were upregulated, and genes involved in iron transport were repressed. Expression of toxins and colonization factors were not changed, suggesting retained virulence. Metabolomic analyses showed that the transient phase was characterized by a drop of intracellular amino acids, e.g., L-tyrosine, L-tryptophan, L-phenylalanine, L-leucine, and L-glutamic acid, followed by increased levels at induction of stationary phase. A pathway enrichment analysis of the entire transcriptome and metabolome showed activation of pathways involved in the degradation of neurotransmitters aminobutyrate (GABA) and precursors of 5-hydroxytryptamine (serotonin). This work provides a comprehensive framework for further studies on transcriptional and metabolic regulation in pathogenic E. coli. ImportanceWe show that E. coli, exemplified by the pathogenic subspecies enterotoxigenic E. coli (ETEC), undergoes a stepwise transcriptional and metabolic transition into the stationary phase. At a specific entry point, E. coli induces activation and repression of specific pathways. This leads to a rapid decrease of intracellular levels of L-tyrosine, L-tryptophan, L-phenylalanine, L-leucine, and L-glutamic acid due to metabolism into secondary compounds. The resulting metabolic activity leads to an intense but short peak of indole production, suggesting that this is the previously described "indole peak," rapid decrease of intermediate molecules of bacterial neurotransmitters, increased putrescine and fucose uptake, increased glutathione levels, and decreased iron uptake. This specific transient shift in gene expression and metabolomics is short-lived and disappears when bacteria enter the stationary phase. We suggest it mainly prepares bacteria for ceased growth, but the pathways involved suggest that this transient phase substantially influences survival and virulence.

microbiology↗

bioRxiv2021

Evidence for the Presence of Hyphae and Fruiting Body Calcium Oxalate Crystallites in Schizophyllum commune

Biomineralization is a phenomenon in which organisms form crystals. Studies have shown that many fungi have the ability to biomineralize, it can exhibit calcium oxalate crystals on their hyphae and fruiting body. Schizophyllum commune is a common saprophytic fungus distributed all over the world, but there is little research on its biomineralization. In this paper, S. commune fruiting body from three different provinces of China were collected, and isolation for hyphal cultured to obtain several samples. Utilizing light microscope, FE-SEM, and EDAX, the existence of crystals on the fruiting body and mycelium of each strain was found, and their morphological characteristics and ion content were analyzed. It was ultimately established that biomineralization occurs on S. commune.

biochemistry↗

bioRxiv2021

Rapid Directed Molecular Evolution of Fluorescent Proteins in Mammalian Cells

In vivo imaging of model organisms is heavily reliant on fluorescent proteins with high intracellular brightness. Here we describe a practical method for rapid optimization of fluorescent proteins via directed molecular evolution in cultured mammalian cells. Using this method, we were able to perform screening of large gene libraries containing up to 2{middle dot}107 independent random genes of fluorescent proteins expressed in HEK cells completing one iteration directed evolution in a course of [~]8 days. We employed this approach to develop a set of green and near-infrared fluorescent proteins with enhanced intracellular brightness. The developed near-infrared fluorescent proteins demonstrated high performance for fluorescent labeling of neurons in culture and in vivo in model organisms such as C.elegans, Drosophila, zebrafish, and mice. Spectral properties of the optimized near-infrared fluorescent proteins enabled crosstalk-free multicolor imaging in combination with common green and red fluorescent proteins, as well as dual-color near-infrared fluorescence imaging. The described method has a great potential to be adopted by protein engineers due to its simplicity and practicality. We also believe that the new enhanced fluorescent proteins will find wide application for in vivo multicolor imaging of small model organisms.

molecular biology↗

bioRxiv2021

Dice-XMBD: Deep learning-based cell segmentation for imaging mass cytometry

Highly multiplexed imaging technology is a powerful tool to facilitate understanding cells composition and interaction in tumor microenvironment at subcellular resolution, which is crucial for both basic research and clinical applications. Imaging mass cytometry (IMC), a multiplex imaging method recently introduced, can measure up to 40 markers simultaneously in one tissue section by using a high-resolution laser with a mass cytometer. However, due to its high resolution and large number of channels, how to process and interpret the image data from IMC remains a key challenge for its further applications. Accurate and reliable single cell segmentation is the first and a critical step to process IMC image data. Unfortunately, existing segmentation pipelines either produce inaccurate cell segmentation results, or require manual annotation which is very time-consuming. Here, we developed Dice-XMBD, a Deep learnIng-based Cell sEgmentation algorithm for tissue multiplexed imaging data. In comparison with other state-of-the-art cell segmentation methods currently used in IMC, Dice-XMBD generates more accurate single cell masks efficiently on IMC images produced with different nuclear, membrane and cytoplasm markers. All codes and datasets are available at https://github.com/xmuyulab/Dice-XMBD.

bioinformatics↗

bioRxiv2021

Metabolic Complementation between Glucose and Amino Acid Drives Hepatic De Novo Lipogenesis and Steatosis

Increased de novo lipogenesis (DNL) is a hallmark of nonalcoholic fatty liver disease (NAFLD) in obesity, but the macronutrient source for >80% carbon backbone for fatty acid synthesis has not been determined. Here we take an integrated approach to dissect nutrient metabolism, both ex vivo and in vivo. We discover a castling effect of glucose and glutamine metabolism through ex vivo isotope tracing studies that limits the entrance of glucose carbon into the glutamine-dominated tricarboxylic acid cycle (TCA) and DNL pathways. In vivo tracing studies with a high carbohydrate drink (glucose/amino acid, 3:1, w/w) confirm dietary amino acids are twice more efficient than glucose in labeling the hepatic acetyl-CoA and fatty acid pool, and together they account for over 70% of hepatic DNL substrate. Both glucose and glutamine carbon flux into DNL pathways are increased in obese hepatocytes, and metabolic rerouting of substrate carbon toward glycogen synthesis and energy production through GYS2 and GLUD1 overexpression improves hepatic steatosis. Together, these data reveal the quantitative contribution of glucose and amino acid carbon toward hepatic DNL and the development of hepatic steatosis in obesity.

biochemistry↗

bioRxiv2021

Reversion of antibiotic resistance in drug-resistant bacteria using non-steroidal anti-inflammatory drug benzydamine

Antimicrobial resistance has been a growing concern that gradually undermines our tradition treatment regimen. The fact that few antibacterial drugs with new scaffolds or targets have been approved in the past two decades aggravates this crisis. Repurposing previously approved drugs as potent antibiotic adjuvants offers a cost-effective strategy to mitigate the development of resistance and tackle the increasing infections by multidrug-resistant (MDR) bacteria. Herein, we found that benzydamine, a widely used non-steroidal anti-inflammatory drug in clinic, remarkably potentiated broad-spectrum antibiotic-tetracyclines activity against a panel of clinical important resistant pathogens, including MRSA, VRE, MCRPEC and tet(X)-positive Gram-negative bacteria. Further mechanistically experiments showed that benzydamine dissipated membrane potential ({Delta}{Psi}) in both Gram-positive and negative bacteria, which in turn upregulated the transmembrane proton gradient ({Delta}pH) and promoted the uptake of tetracyclines. Additionally, benzydamine exacerbated the oxidative stress by triggering the production of ROS and suppressing GAD system-mediated oxidative defensive. This mode of action explains the great bactericidal activity of the doxycycline-benzydamine combination against different metabolic states of bacteria including persister cells. As a proof-of-concept, the in vivo efficacy of this combination therapy was evidenced in multiple animal infection models. These findings revealed that benzydamine is a promising tetracycline antibiotics adjuvant and has the potential to address life-threatening infections by MDR bacteria.

microbiology↗

bioRxiv2021

High arsenic levels increase activity rather than diversity or abundance of arsenic metabolism genes in paddy soils

Arsenic (As) metabolism genes are generally present in soils but their diversity, relative abundance, and transcriptional activity in response to different As concentrations remain unclear, limiting our understanding of the microbial activities that control the fate of an important environmental pollutant. To address this issue, we applied metagenomics and metatranscriptomics to paddy soils showing a gradient of As concentrations to investigate As resistance genes (ars) including arsR, acr3, arsB, arsC, arsM, arsI, arsP, and arsH as well as energy-generating As respiratory oxidation (aioA) and reduction (arrA) genes. Somewhat unexpectedly, the relative DNA abundances and diversity of ars, aioA, and arrA genes were not significantly different between low and high ([~]10 vs [~]100 mg kg-1) As soils. By comparison to available metagenomes from other soils, geographic distance rather than As levels drove the different compositions of microbial communities. Arsenic significantly increased ars genes abundance only when its concentration was higher than 410 mg kg-1. In contrast, between low and high As soils, metatranscriptomics revealed a significant increase in transcription of ars and aioA genes, which are induced by arsenite, the dominant As species in paddy soils, but not arrA genes, which are induced by arsenate. These patterns appeared to be community-wide as opposed to taxon-specific. Collectively, our findings advance understanding of how microbes respond to high As levels and the diversity of As metabolism genes in paddy soils and indicated that future studies of As metabolism in soil, or other environments, should include the function (transcriptome) level. IMPORTANCEArsenic (As) is a toxic metalloid pervasively present in the environment. Microorganisms have evolved the capacity to metabolize As, and As metabolism genes are ubiquitously present in the environment even in the absence of high concentrations of As. However, these previous studies were carried out at the DNA level and thus, the activity of the As metabolism genes detected remains essentially speculative. Here, we show that the high As levels in paddy soils increased the transcriptional activity rather than the relative DNA abundance and diversity of As metabolism genes. These findings advance our understanding of how microbes respond to and cope with high As levels, and have implications for better monitoring and managing an important toxic metalloid in agricultural soils and possibly other ecosystems.

microbiology↗

bioRxiv2021

Genome-wide CRISPR activation screen identifies novel receptors for SARS-CoV-2 entry

The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been endangering worldwide public health and economy. SARS-CoV-2 infects a variety of tissues where the known receptor ACE2 is low or almost absent, suggesting the existence of alternative pathways for virus entry. Here, we performed a genome-wide barcoded-CRISPRa screen to identify novel host factors that enable SARS-CoV-2 infection. In addition to known host proteins, i.e. ACE2, TMPRSS2 and NRP1, we identified multiple host components, among which LDLRAD3, TMEM30A and CLEC4G were confirmed as functional receptors for SARS-CoV-2. All these membrane proteins bind directly to spikes N-terminal domain (NTD). Their essential and physiological roles have all been confirmed in either neuron or liver cells. In particular, LDLRAD3 and CLEC4G mediate SARS-CoV-2 entry and infection in a fashion independent of ACE2. The identification of the novel receptors and entry mechanisms could advance our understanding of the multiorgan tropism of SARS-CoV-2, and may shed light on the development of the therapeutic countermeasures against COVID-19.

microbiology↗

bioRxiv2021

Circular RNA Vaccines against SARS-CoV-2 and Emerging Variants

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its emerging variants of concern (VOC), such as Delta (B.1.617.2) and Omicron (B.1.1.529), has continued to drive the worldwide pandemic. Therefore, there is a high demand for vaccines with enhanced efficacy, high thermostability, superior design flexibility, and fast manufacturing speed. Here, we report a circular RNA (circRNA) vaccine that encodes the trimeric RBD of SARS-CoV-2 Spike protein. Without the need of nucleotide modification, 5-capping or 3-polyadenylation, circRNA could be rapidly produced via in vitro transcription and is highly thermostable whether stored in naked or lipid-nanoparticle (LNP)-encapsulated format. LNP-encapsulated circRNARBD elicited potent neutralizing antibodies and T cell responses, providing robust protection against Beta (B.1.351) and native viruses in mice and rhesus macaques, respectively. Notably, circRNA vaccine enabled higher and more durable antigen production than 1m{Psi}-modified mRNA vaccine, eliciting a higher proportion of neutralizing antibodies and stronger Th1-biased immune responses. Importantly, we found that circRNARBD-Omicron vaccine induced effective neutralizing antibodies against only Omicron but not Delta variant. By contrast, circRNARBD-Delta could elicit high level of neutralizing antibodies against both Delta and Omicron. Following two doses of either native- or Delta-specific vaccination, circRNARBD-Delta, but not Omicron or Beta vaccines, could effectively boost the neutralizing antibodies against both Delta and Omicron variants. These results suggest that circRNARBD-Delta is a favorable choice for vaccination to provide a broad-spectrum protection against the current variants of concern of SARS-CoV-2.

immunology↗

bioRxiv2021

A global multiregional proteomic map of the human cerebral cortex

The Brodmann area (BA)-based map is one of the most widely used cortical maps for studies of human brain functions and in clinical practice; however, the molecular architecture of BAs remain unknown. The present study provided a global multiregional proteomic map of the human cerebral cortex by analyzing 29 BAs. These 29 BAs were grouped into 6 clusters based on similarities in proteomic patterns: the motor and sensory cluster, vision cluster, auditory cluster and Brocas area, Wernickes area cluster, cingulate cortex cluster, and heterogeneous function cluster. We identified 474 cluster-specific and 134 BA-specific signature proteins whose functions are closely associated with specialized functions and disease vulnerability of the corresponding cluster or BA. The findings of the present study could provide explanations for the functional connections between the anterior cingulate cortex and sensorimotor cortex and for anxiety-related function in the sensorimotor cortex. The brain transcriptomic and proteomic comparison indicated that they both could reflect the function of cerebral cortex, but showed different characteristics. These proteomic data are publicly available at the Human Brain Proteome Atlas (www.brain-omics.com). Our results may enhance our understanding of the molecular basis of brain functions and provide an important resource to support human brain research.

neuroscience↗

bioRxiv2020

A cancer cell-intrinsic GOT2-PPARδ axis suppresses antitumor immunity

Despite significant recent advances in precision medicine1,2, pancreatic ductal adenocarcinoma (PDAC) remains near-uniformly lethal. While the most frequent genomic alterations in PDAC are not presently druggable3 and conventional therapies are often ineffective in this disease4, immune-modulatory therapies hold promise to meaningfully improve outcomes for PDAC patients. Development of such therapies requires an improved understanding of the immune evasion mechanisms that characterize the PDAC microenvironment, including frequent exclusion of antineoplastic T cells and abundance of immune-suppressive myeloid cells5-9. Here we show that cancer cell-intrinsic glutamic-oxaloacetic transaminase 2 (GOT2) shapes the immune microenvironment to suppress antitumor immunity. Mechanistically, we find that GOT2 functions beyond its established role in the malate-aspartate shuttle10-13 and promotes the transcriptional activity of nuclear receptor peroxisome proliferator-activated receptor delta (PPAR{delta}), facilitated by direct fatty acid binding. While GOT2 in PDAC cells is dispensable for cancer cell proliferation in vivo, GOT2 loss results in T cell-dependent suppression of tumor growth, and genetic or pharmacologic activation of PPAR{delta} restores PDAC progression in the GOT2-null context. This cancer cell-intrinsic GOT2-PPAR{delta} axis promotes spatial restriction of both CD4+ and CD8+ T cells from the tumor microenvironment, and fosters the immune-suppressive phenotype of tumor-infiltrating myeloid cells. Our results demonstrate a non-canonical function for an established mitochondrial enzyme in transcriptional regulation of immune evasion, which may be exploitable to promote a productive antitumor immune response.

cancer biology↗

bioRxiv2020

The position of single-base deletions in the VNTR sequence of the carboxyl ester lipase (CEL) gene determines pathogenicity

Variable number of tandem repeat (VNTR) sequences present in the genome can have functional consequences that contribute to human disease. This is the case for the CEL gene, which encodes the digestive enzyme carboxyl ester lipase. CEL has a VNTR located in exon 11, and rare single-base deletions (DELs) within this region cause MODY8, an inherited disorder characterized by exocrine pancreatic dysfunction and diabetes. Here, we have studied how the position of single-base deletions within the CEL VNTR affects the proteins pathogenic properties. We investigated four naturally occurring CEL variants with single-base deletions in different VNTR segments (DEL1, DEL4, DEL9, DEL13), of which only DEL1 and DEL4 have been observed in MODY8 patients. When expressed in a cellular model system, only DEL1 and DEL4 exhibited significantly reduced secretion and increased intracellular aggregation compared to normal CEL. We found that all DEL variants had slightly decreased enzymatic activity and that their level of O-glycosylation was affected. Moreover, only DEL1 and DEL4 significantly increased endoplasmic reticulum (ER) stress. In conclusion, CEL single-base deletion variants have the highest pathogenic potential when the mutational event has taken place in the proximal VNTR part, resulting in the longest aberrant protein tails. Thus, DEL1 and DEL4 are pathogenic CEL variants, whereas we consider DEL13 as benign and DEL9 as likely benign. These findings have implications for our understanding of how CEL mutations cause pancreatic disease through protein misfolding and proteotoxicity, leading to ER stress and activation of the unfolded protein response.

cell biology↗

bioRxiv2020

The genomic formation of First American ancestors in East and Northeast Asia

Upward Sun River 1, an individual from a unique burial of the Denali tradition in Alaska (11500 calBP), is considered a type representative of Ancient Beringians who split from other First Americans 22000-18000 calBP in Beringia. Using a new admixture graph model-comparison approach resistant to overfitting, we show that Ancient Beringians do not form the deepest American lineage, but instead harbor ancestry from a lineage more closely related to northern North Americans than to southern North Americans. Ancient Beringians also harbor substantial admixture from a lineage that did not contribute to other Native Americans: Amur River Basin populations represented by a newly reported site in northeastern China. Relying on these results, we propose a new model for the genomic formation of First American ancestors in Asia. One Sentence SummaryAncient Beringians do not form the deepest American lineage, but harbor admixture from Amur River Basin populations.

genetics↗

bioRxiv2020

Dscam1 promotes blood cell survival in Drosophila melanogaster through a dual role in blood cells and neurons

Down Syndrome Cell Adhesion Molecule 1 (Dscam1) is a receptor-like cell adhesion molecule that is conserved across the animal kingdom, but its roles in hematopoiesis remain unknown. Dscam1 related genes in vertebrates and invertebrates are key regulators of neuron morphogenesis and neuronal tiling. In Drosophila, Dscam1 in addition has roles in blood cells (hemocytes) in innate immunity and phagocytosis of pathogens. Given the anatomical and functional role of peripheral sensory neurons as microenvironments for resident hematopoietic sites in the Drosophila larva, we sought to investigate the role of Dscam1 in this context. Interestingly, we find that Dscam1 fills the role of a previously anticipated factor in neuron-hemocyte communication that supports trophic survival: tissue specific silencing of Dscam1 by in vivo RNAi in sensory neurons leads to neuron reduction, which in turn results in reduced hemocyte numbers due to apoptosis. Dscam1 silencing in hemocytes also results in a reduction of hemocytes and increased apoptosis. This cell-autonomous effect of Dscam1 silencing can be mimicked by RNAi silencing of dreadlocks (dock), suggesting that intracellular Dscam1 signaling relies on the adapter protein Dock in this system. Our findings reveal a dual role for Dscam1 in Drosophila hematopoiesis, by promoting survival of the sensory neuron microenvironments that in turn support hemocyte survival, and by promoting survival of hemocytes cell-autonomously. It will be interesting to explore possible functions of vertebrate Dscam1 related genes such as DSCAML1 in blood cells and their trophic survival.

developmental biology↗

bioRxiv2020

Unexpectedly high mutation rate of a deep-sea hyperthermophilic anaerobic archaeon

Deep-sea hydrothermal vents resemble the early Earth, and thus the dominant Thermococcaceae inhabitants, which occupy an evolutionarily basal position of the archaeal tree and take an obligate anaerobic hyperthermophilic free-living lifestyle, are likely excellent models to study the evolution of early life. Here, we determined that unbiased mutation rate of a representative species, Thermococcus eurythermalis, exceeded that of all known free-living prokaryotes by 1-2 orders of magnitude, and thus rejected the long-standing hypothesis that low mutation rates were selectively favored in hyperthermophiles. We further sequenced multiple and diverse isolates of this species and calculated that T. eurythermalis has a lower effective population size than other free-living prokaryotes by 1-2 orders of magnitude. These data collectively indicate that the high mutation rate of this species is not selectively favored but instead driven by random genetic drift. The availability of these unusual data also helps explore mechanisms underlying microbial genome size evolution. We showed that genome size is negatively correlated with mutation rate and positively correlated with effective population size across 30 bacterial and archaeal lineages, suggesting that increased mutation rate and random genetic drift are likely two important mechanisms driving microbial genome reduction. Future determinations of the unbiased mutation rate of more representative lineages with highly reduced genomes such as Prochlorococcus and Pelagibacterales that dominate marine microbial communities are essential to test these hypotheses.

microbiology↗

bioRxiv2020

Diversity and biogeography of Woesearchaeota: A comprehensive analysis of multi-environment data

Woesearchaeota is a newly proposed archaeal phylum frequently detected in various environments. Due to the limited systematical study, little is known about their distribution, taxonomy, and metabolism. Here, we conducted a comprehensive study for Woesearchaeota with 16S ribosomal RNA (rRNA) gene sequencing data of 27,709 samples and metagenomic whole genome sequencing (WGS) data of 1,266 samples. We find that apart from free-living environments, Woesearchaeota also widely distribute in host-associated environments. And host-associated environmental parameters greatly affect their distribution. 81 Woesearchaeota genomes, including 33 genomes firstly reconstructed in this project, were assigned to 59 Woesearchaeota species, suggesting their high taxonomic diversity. Comparative analysis indicated that Woesearchaeota have an open pan-genome with small core genome. Metabolic reconstruction showed that particular metabolic pathway absence in specific environments, demonstrated the metabolic diversity of Woesearchaeota varies in differences environments. These results have placed host-associated environments into the global biogeography of Woesearchaeota and have demonstrated their genomic diversity for future investigation of adaptive evolution.

ecology↗