Biology subjects

Guo, L.

Publications and source records attributed to Guo, L..

At least 163 records · Page 9Linked to original sources

bioRxiv2022

KapBeta2 is a modifier of the C9orf72-linked glycine-arginine dipeptide neurotoxicity

SummaryExpanded intronic G4C2 repeats in the C9orf72 gene cause several cases of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). These repeats are translated through a non-AUG-dependent mechanism into five different dipeptides (DPRs), including poly-glycine-arginine (GR), which is aggregation-prone and eventually neurotoxic. Here, we report that Kap{beta}2 and GR interact, co-aggregating in primary neurons in-vitro and CNS tissue in-vivo. Importantly, this interaction improves the overall survival of neurons expressing GR. Downregulation of Kap {beta}2 is detrimental to the survival of neurons only if GR is expressed, whereas increased Kap {beta}2 levels mitigate GR-mediated neurotoxicity. notably, we did not find any changes in TDP-43 localization nor in the dynamic properties of the GR aggregates when Kap{beta}2 was over-expressed. These findings support the design of therapeutic strategies aimed at modulating Kap {beta}2 levels as a potential new avenue for contrasting neurodegeneration in C9orf72-ALS/FTD.

neuroscience↗

bioRxiv2022

The effector recognition by synthetic sensor NLR receptors requires the concerted action of multiple interfaces within and outside the integrated domain

Plant sensor nucleotide-binding leucine-rich repeat (NLR) receptors detect pathogen effectors through their integrated domains (IDs). The RGA5 sensor NLR recognizes its corresponding effectors AVR-Pia and AVR1-CO39 from the blast fungus Magnaporthe oryzae through direct binding to its heavy metal-associated (HMA) ID to trigger the RGA4 helper NLR-dependent resistance in rice. Here we report a mutant of RGA5 named RGA5HMA5 that confers complete resistance in transgenic rice plants to the M. oryzae strains expressing the noncorresponding effector AVR-PikD. RGA5HMA5 carries three engineered interfaces, two of which lie in the HMA ID and the other in the C-terminal Lys-rich stretch tailing the ID. However, the RGA5 variants having one or two of the three interfaces, including replacing all the Lys residues with Glu residues in the Lys-rich stretch, failed to activate RGA4-dependent cell death of rice protoplasts. Altogether, this work demonstrates that sensor NLRs require a concerted action of multiple surfaces within and outside the IDs to both recognize noncorresponding effectors and activate helper NLR-mediated resistance, and has implications in structure-guided designing of sensor NLRs.

plant biology↗

bioRxiv2022

Evolution of insecticide resistance via parallel amino acid substitutions in insect pests and their parasitoid wasps

Insecticides have become the primary selective force in many insect species; however, whether beneficial insects developed resistance remains unknown. We analyzed the sequences of hymenopteran GABAA receptor subunit gene Rdl (resistance to dieldrin), which encodes the target of cyclodiene and phenylpyrazole insecticides. The resistance-conferring A2 S mutations were found in seven parasitoid wasps and similar amino acid replacements at homologous sites have been identified in four of their resistant hosts. Our findings indicate how parallel molecular evolution at a single amino acid site confers adaptation in both insects and their natural enemies, which may shape species interactions and community structure.

ecology↗

bioRxiv2022

Telomere dysfunction impairs intestinal differentiation andpredisposes to diet-induced colitis

Intestinal epithelium dysfunction causes barrier defects, malabsorption and dysbiosis, predicting local and systemic disease, morbidity and mortality in humans. However, the underlying causes are not well understood. Here we show that telomere shortening is a host intrinsic factor that impairs enterocyte differentiation. The presence of such undifferentiated enterocytes is associated with barrier disruption and malabsorption of nutrients, such as fructose. A fructose-rich diet causes increased fructose spillover to the colon and induces colitis in a microbiome-dependent manner. The microbiome uses fructose to synthesize essential metabolites, including NAD precursors, that complement the hosts low NAD pool in the inflamed colon. Thus, telomere shortening drives enterocyte dysfunction and predisposes to diet-induced colitis through barrier disruption, increased nutrient flux to the colon and modulation of the microbiome. This differerentiation defect expands the canonical stem cell failure-centered view of how telomere shortening impacts the intestine and predisposes to intestinal disease in conditions associated with short telomeres.

cell biology↗

bioRxiv2022

Identification of novel basil downy mildew resistance genes using de novo comparative transcriptomics

O_LISweet basil (Ocimum basilicum L.) production is threatened by the oomycete pathogen Peronospora belbahrii causing basil downy mildew (BDM); BDM resistant cultivar Mrihani (MRI) was identified in a germplasm screen, and fertile progeny were produced through a breeding program with BDM-susceptible Newton (SB22), but the molecular mechanisms conferring resistance in MRI and progeny remained unknown C_LIO_LIComparative transcriptomics was performed to identify candidate resistance genes and potential mechanisms for BDM resistance; RNA samples from BDM-infected MRI and SB22 plants were harvested at 4 time points during the first 3 days of infection to differentiate interactions in resistant and susceptible plants. C_LIO_LIThree categories of genes uniquely induced in resistant MRI upon pathogen challenge were identified: nucleotide-binding leucine rich repeat proteins (NLRs), multi-functional receptor-like kinases (RLKs), and secondary metabolic enzymes; validation of the top resistance candidate NLR gene confirmed its unique presence in MRI as well as in two of four resistant MRIxSB22 F2 progeny. C_LIO_LIIn MRI, pathogen challenge also upregulated transcripts in the salicylic acid synthesis pathway, suggesting its role in BDM resistance, and demonstrating the application of using comparative transcriptomics to identify resistance genes and mechanisms in non-model crops for marker-assisted breeding approaches. C_LI

plant biology↗

bioRxiv2022

Neuroinflammation in neuronopathic Gaucher disease: Role of microglia and NK cells

BackgroundNeuronopathic Gaucher Disease (nGD) is a rare neurodegenerative disorder caused by biallelic mutations in Gba, and buildup of glycosphingolipids in lysosomes. Neuronal injury and cell death are prominent pathological features, however the role of Gba in individual cell types and involvement of microglia, blood derived macrophages and immune infiltrates in nGD pathology remains enigmatic. MethodsHere, using single cell resolution of mouse nGD brains, we found induction of neuroinflammation pathways involving microglia, NK cells, astrocytes, and neurons. ResultsTargeted rescue of Gba in microglia and in neurons, respectively in Gba deficient, nGD mice reversed the buildup of glucosylceramide (GlcCer) and glucosylsphingosine (GlcSph), concomitant with amelioration of neuroinflammation, reduced level of serum neurofilament light chain (Nf-L) and improved survival. The levels of bioactive lipid, GlcSph was strongly correlated with serum Nf-L and ApoE in nGD mouse models as well as GD patients. Gba rescue in microglia/macrophage compartment prolonged survival, that was further enhanced upon treatment with brain permeant inhibitor of glucosylceramide synthase, effects mediated via improved glycosphingolipid homeostasis and reversal of neuroinflammation involving activation of microglia, brain macrophages and NK cells. ConclusionsTogether, our study delineates individual cellular effects of Gba deficiency in nGD brains, highlighting the central role of neuroinflammation driven by microglia activation and the role of brain permeant small molecule glucosylceramide inhibitor in reversing complex multidimensional pathophysiology of nGD. Our findings advance disease biology whilst identifying compelling biomarkers of nGD to improve patient management, enrich clinical trials and illuminate therapeutic targets. FundingResearch grant from Sanofi Genzyme; other support includes R01NS110354.Yale Liver Center P30DK034989, pilot project grant.

immunology↗

bioRxiv2022

The tissue-specific chromatin accessibility landscape of Papaver somniferum

Accessible chromatin regions (ACRs) at promoters, enhancers, and other gene regulatory regions allow transcription factors (TFs) to bind, which regulate gene transcription involved in plant development and metabolism. Papaver somniferum has been widely applied in clinical medicine as one of the most important and oldest medicinal plants due to its unique and effective active ingredients. However, the transcriptional regulatory mechanism of tissue-specific distribution of active ingredients remains unknown. In this study, transcriptome and chromatin accessibility analysis by RNA sequencing (RNA-seq) and assay for transposase-accessible chromatin sequencing (ATAC-seq) was performed to investigate these underlying molecular mechanisms. We identified tissue-specific chromatin Tn5 hypersensitive site (THS) and gene expression by examining the variation of THS and transcripts across six tissues (capsule, stem, fine root, tap root, leaf, and petal). Our results provide insight into the epigenetic mechanism of transcriptional plasticity for P. somniferum organ development. Sequence motif analysis within accessible chromatin regions for co-expressed gene modules revealed enriched binding sites of hub transcription factors that regulate tissue-specific functions. Furthermore, we identified regulatory elements for tissue-specific accumulation of morphine and noscapine in P. somniferum. This is the first tissue-specific chromatin accessibility landscape of P. somniferum providing an important resource for functional epigenetic analysis and future molecular breeding in P. somniferum for variety improvement.

plant biology↗

bioRxiv2022

Comparative analysis about the structure of complete chloroplast genomes in genus Mangifera and accuracy verification about phylogenetic analysis based on gene ycf2 in genus level

Mango is an evergreen plant belonging to the genus Mangifera of the Anacardiaceae family. Genus Mangifera has 69 species of Mangifera around the world that are mainly distributed in tropical and subtropical countries, including India, Indonesia, the Malay Peninsula, Thailand, and South China. It is a popular tropical fruit known as the "King of Tropical Fruits". However, the study of the structure information of the complete chloroplast genome of Mangifera was microscopic, there was no report about the comparison of SSR, Ka/Ks, codons analysis and RNA editing, so in this study, we sequenced the 6 Mangifera samples and used three different ways to analyze the relationship of 6 species of Mangifera. Then we got some results, through the RNA editing and Ka/Ks calculating, we found the species could be divided into two groups, and the difference between the two groups was protein-coding gene ccsA. Moreover, all RNA editing occurred conversion of C to T and the gene ndhB had the most RNA editing sites in all species. In Ka/Ks analysis, the gene atpB, cemA, clpP, ndhD, petD, petB and ycf15 would be suffered from the positive selection after divergence. We also find the IR regions in these seven samples were very conservation through IR contraction and expansion and Sequence Divergence Analysis. Finally, we tried to confirm the relationship between 7 samples of Mangifera in Angiosperms in 3 different ways. Then we got that ML210 and MP090 had a closer relationship than others, MS796 had a closer relationship with ML210 and MP090 than others. At the same time, the method of phylogenetic analysis based on the gene ycf2 was not more accurate at the genus level than the method based on complete cp genome and proteincoding genes.

molecular biology↗

bioRxiv2022

Inhibition of the IL-17A axis Protects against Immune-related Adverse Events while Supporting Checkpoint Inhibitor Anti-tumor Efficacy

Checkpoint inhibitor (ICI) immunotherapy leverages the bodys own immune system to attack cancer cells but leads to unwanted autoimmune side effects in up to 60% of patients. Such immune related adverse events (IrAE) may lead to treatment interruption, permanent organ dysfunction, hospitalization and premature death. Thyroiditis is one of the most common IrAE, but the cause of thyroid IrAE remains unknown. Here we present a novel mouse model in which checkpoint inhibitor therapy leads to multi-organ autoimmune infiltrates and show that activation and infiltration of Type 3 immune cells including IL17A+ ROR{gamma}t+ CD4+ (T helper 17 or Th17) and gamma delta 17 ({gamma}{delta}T17) T cells promote thyroid IrAE development. IL-17A+ T cells were similarly found in thyroid specimens from cancer patients treated with ICI who developed thyroid IrAE. Furthermore, antibody-based inhibition of IL-17A, a clinically available therapy, significantly reduced thyroid IrAE development in ICI-treated mice. Finally, combination of IL-17A neutralization with ICI treatment in multiple tumor models did not reduce ICI anti-tumor efficacy. These studies suggest that targeting Th17 and {gamma}{delta}17 function may reduce IrAE without impairing ICI anti-tumor efficacy and may be a generalizable strategy to address IL17-mediated IrAE.

immunology↗

bioRxiv2022

Cell- and non-cell-autonomous ARF3 coordinates meristem proliferation and organ patterning in Arabidopsis

In cell-cell communication, non-cell-autonomous transcription factors play vital roles in controlling plant stem cell fate. We previously reported that AUXIN RESPONSE FACTOR 3 (ARF3), a member of the ARF family with critical roles in floral meristem maintenance and determinacy, has a distinct accumulation pattern that differs from the expression domain of its encoding gene in the shoot apical meristem (SAM). However, the biological meaning of this difference is obscure. Here, we demonstrate that ARF3 expression is mainly activated at the periphery of the SAM by auxin, where ARF3 cell-autonomously regulates the expression of meristem-organ boundary-specific genes, such as CUP-SHAPED COTYLEDON1-3 (CUC1-3), BLADE ON PETIOLE1-2 (BOP1-2) and TARGETS UNDER ETTIN CONTROL3 (TEC3) to determine organ patterning. We also show that ARF3 is translocated into the organizing center, where it represses cytokinin activity and WUSCHEL expression to regulate meristem activity non-cell-autonomously. Therefore, ARF3 acts as a molecular link that mediates the interaction of auxin and cytokinin signaling in the SAM while coordinating the balance between meristem maintenance and organogenesis. Our findings reveal an ARF3-mediated coordination mechanism through cell-cell communication in dynamic SAM maintenance.

developmental biology↗

bioRxiv2021

Geminivirus C4 proteins inhibit GA signaling via prevention of NbGAI degradation, to promote viral infection and symptom development in N. benthamiana

Phytohormone gibberellin (GA) is an important plant signaling molecule that regulates plant growth and defense against abiotic and biotic stresses. To date, the molecular mechanism of the plant responses to viral infection mediated by GA is still undetermined. DELLA is a repressor of GA signaling and is recognized by the F-box protein, a component of the SCFSLY1/GID2 complex. The recognized DELLA is degraded by the ubiquitin-26S proteasome, leading to the activation of the GA signaling. Here, we report that ageratum leaf curl Sichuan virus (ALCScV)-infected N. benthamiana plants showed dwarfing symptom and abnormal flower development. The infection of ALCScV alters the expressions of GA pathway-related genes and decreases the content of endogenous GA significantly in N. benthamiana. Further, ALCScV-encoded C4 protein interacts with the DELLA protein NbGAI, and interferes with the interaction between NbGAI and NbGID2 to prevent the degradation of NbGAI, leading to the inhibition of the GA signaling pathway. Silencing of NbGAI or exogenous GA3 treatment significantly reduces viral accumulation and disease symptoms in N. benthamiana plants. The same results were proved by the experiments with C4 protein encoded by tobacco curly shoot virus (TbCSV). Therefore, we propose a novel mechanism of geminivirus C4 proteins controling virus infection and disease symptom development through interfering GA signaling pathway. Author SummaryGibberellins (GAs) are plant hormones that are essential for many developmental processes in plants. It has indicated that plant virus infection can induce abnormal flower development and influence GA pathway resulting the plant dwarfing symptom, but the underlying mechanisms is still not well described. Here, we demonstrate that geminivirus - encoded C4 protein regulates the GA signaling pathway to promote viral accumulation and disease symptom development. Through directly interacting with NbGAI, the C4 protein interferes with the interaction between NbGAI and NbGID2, which inhibits the degradation of NbGAI. As a result, the GA signaling pathway is blocked, and the infected plants display symptoms of typical dwarfing and delayed flowering. Our results reveal a novel mechanism by which geminivirus C4 proteins influence viral pathogenicity via interfering the GA signaling pathway, and provide new insights into the interaction between virus and host.

pathology↗

bioRxiv2021

Potential inhibitors for blocking the interaction of the coronavirus SARS-CoV-2 spike protein and its host cell receptor ACE2

The outbreak of SARS-CoV-2 continues to pose a serious threat to human health and social and economic stability. In this study, we established an anti-coronavirus drug screening platform based on the Homogeneous Time Resolved Fluorescence (HTRF) technology and the interaction between the coronavirus S protein and its host receptor ACE2. This platform is a rapid, sensitive, specific, and high throughput system. With this platform, we screened two compound libraries of 2,864 molecules and identified three potential anti-coronavirus compounds: tannic acid (TA), TS-1276 (anthraquinone), and TS-984 (9-Methoxycanthin-6-one). Our in vitro validation experiments indicated that TS-984 strongly inhibits the interaction of the coronavirus S-protein and the human cell ACE2 receptor. This data suggests that TS-984 is a potent blocker of the interaction between the S-protein and ACE2, which might have the potential to be developed into an effective anti-coronavirus drug. SIGNIFICANCEThe ongoing pandemic of COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made a serious threat to public health worldwide. Given the urgency of the situation, researchers are attempting to repurpose existing drugs for treating COVID-19. In this present study, we screened two compound libraries of 2,864 molecules and identified a potent inhibitor (TS-984) for blocking the coronavirus S-protein and the human cell ACE2 receptor. TS-984 might have the potential to be developed into an effective anti-coronavirus drug for treating COVID-19.

pharmacology and toxicology↗

bioRxiv2021

PncA from bacteria improves diet-induced NAFLD by enabling the transition from NAM to NA in mice

Nicotinamide adenine dinucleotide (NAD+) is crucial for energy metabolism, oxidative stress, DNA damage repair, longevity regulation, and several signaling processes. To date, three NAD+ synthesis pathways have been found in microbiota and hosts, but the potential relationship between gut microbiota and their hosts in regulating NAD+ homeostasis remains unknown. Here, we show that an analog of the first-line tuberculosis drug pyrazinamide (a bacterial NAD+ synthesis inhibitor) affected NAD+ levels in the intestines and liver of mice and disrupted the intestinal microecological balance. Furthermore, using microbiota expressing the pyrazinamidase/nicotinamidase (PncA) gene, which is a target of pyrazinamide, hepatic NAD+ levels were greatly increased and significantly increased compared with other NAD+ precursors, and diet-induced non-alcoholic fatty liver disease (NAFLD) in mice was improved. Overall, the PncA gene in microbiota plays an important role in regulating NAD+ synthesis in the host, thereby providing a potential target for modulating the hosts NAD+ level. HighlightsO_LIPncA inhibitors disrupt gut microbiome homeostasis and reduce host NAD+ levels but do not affect NAD+ levels in cultured cells C_LIO_LIPncA gene in microbiota affects host liver NAD metabolism C_LIO_LIPncA affects lipid metabolism-related genes and metabolites in mice with NAFLD C_LIO_LIDiet-induced NAFLD is improved by PncA overexpression in the liver of mice C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=132 SRC="FIGDIR/small/471202v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@7279aeorg.highwire.dtl.DTLVardef@192a133org.highwire.dtl.DTLVardef@195482forg.highwire.dtl.DTLVardef@1b634a2_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2021

CV-containing vesicle budding from chloroplast inner envelope membrane is mediated by clathrin but inhibited by GAPC

Clathrin-mediated vesicular formation and trafficking are highly conserved in eukaryotic cells and are responsible for molecular cargo transport and signal transduction among organelles. It remains largely unknown whether clathrin-coated vesicles can be generated from chloroplasts. CHLOROPLAST VESICULATION (CV)-containing vesicles (CVVs) generate from chloroplasts and mediate chloroplast degradation under abiotic stress. In this study, we showed that CV interacted with the clathrin heavy chain (CHC) and induced vesicle budding from the chloroplast inner envelope membrane. Defects on CHC2 and the dynamin-encoding DRP1A gene affected CVV budding and releasing from chloroplast. CHC2 is also required for CV-induced chloroplast degradation and hypersensitivity to water stress. Moreover, GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE (GAPC) interacts with CV and impairs the CV-CHC2 interaction. GAPC1 overexpression inhibited CV-mediated chloroplast degradation and hypersensitivity to water stress. CV silencing alleviated the hypersensitivity of gapc1gapc2 plant to water stress. Together, our work revealed a pathway of clathrin-assisted CVV budding from the chloroplast inner envelope membrane, which mediated the stress-induced chloroplast degradation and stress response.

plant biology↗

bioRxiv2021

Microglia ferroptosis is prevalent in neurodegenerative disease and regulated by SEC24B

Iron dysregulation has been implicated in multiple neurodegenerative diseases, including Parkinsons Disease (PD), Amyotrophic Lateral Sclerosis (ALS), and Multiple Sclerosis (MS). One prominent feature of affected brain regions are iron-loaded microglia, but how iron overload influences microglia physiology and disease response is poorly understood. Here we show that microglia are highly susceptible to ferroptosis, an iron-dependent form of cell death. In a tri-culture of human iPSC-derived neurons, astrocytes, and microglia, under ferroptosis-inducing conditions, microglia undergo a drastic shift in cell state, with increased ferritin levels, disrupted glutathione homeostasis, and altered cytokine signaling. Similar ferroptosis-associated signature (FAS) microglia were uncovered in PD, and the signature was also found in a large cohort of PD patient blood samples, raising the possibility that ferroptosis can be identified clinically. We performed a genome-wide CRISPR screen which revealed a novel regulator of ferroptosis, the vesicle trafficking gene SEC24B. A small molecule screen also nominated several candidates which blocked ferroptosis, some of which are already in clinical use. These data suggest that ferroptosis sits at the interface of cell death and inflammation, and inhibition of this process in microglia and other brain cells may provide new ways for treating neurodegenerative disease.

neuroscience↗

bioRxiv2021

Lin28a rejuvenates muscle stem cells via mitochondrial optimization

The well-conserved correlation between juvenility and tissue regeneration was first discussed by Charles Darwin. Ectopic Lin28 is known to play an important role in somatic reprogramming and tissue regeneration, but endogenous Lin28s role in tissue homeostasis and juvenility had remained unclear. Through lineage tracing, we found that a rare subset of muscle stem cells (MuSCs) expressing Lin28a can respond to acute injury by proliferating as Pax3+ or Pax7+ MuSCs, and contribute to all types of myofibers during muscle regeneration. Compared with conventional Pax7+ MuSCs, Lin28a+ MuSCs express more Pax3 and show enhanced myogenicity in vitro. In terms of the epigenetic clock, adult Lin28a+ MuSCs lie between adult Pax7+ MuSCs and embryonic Pax7+ myoblasts according to their DNA methylation profiles. We found that Lin28a+ MuSCs upregulate several embryonic limb bud mesoderm transcription factors and could maintain a juvenile state with enhanced stem cell self-renewal and stress-responsiveness in vitro and in vivo. When combined with telomerase and TP53 inhibition to biomimic mouse Lin28a+ MuSCs, we found that Lin28a can rejuvenate and dedifferentiate aged human primary myoblasts into engraftable, self-renewing MuSCs. Mechanistic studies revealed that Lin28a activated the HIF1A pathway by optimizing mitochondrial ROS (mtROS), thereby rejuvenating MuSC self-renewal and muscle regeneration. Our findings connect the stem cell factor Lin28, mtROS metabolism and stress response pathways to the process of stem cell rejuvenation and tissue regeneration.

cell biology↗

bioRxiv2021

Brain Injury Localization in Electromagnetic Imaging using Symmetric Crossing Lines Method

To avoid death or disability, patients with brain injury should undertake a diagnosis at the earliest time and accept frequent monitoring after starting any medical intervention. This paper presents a novel approach to localize brain injury using the intersection of pairs of signals from symmetrical antennas based on the hypothesis that healthy brains are approximately symmetric that the bleeding targets will lead to significantly different amplitude and phase changes if one of pair of transmit signals cross targets. The scattered signals (S-parameters) are acquired using 100 realistic brain models and 150 experimental data measurements. Firstly, three pair of horizontal antennas are used to detect target crossing which line and in which hemisphere in low frequency bands and estimate the size using high frequency bands. Then, an intersection of two pairs of antennas are identified the position of the target. Finally, a heat map is used to visualise the stroke brain. The results indicate that crossing pairs of antenna signals from the hemisphere with a blood mass exhibit significantly different signal amplitude in the graph features compared to those without the target (p<0.003). The experiments show that our novel localization algorithm can achieve an accuracy of 0.85{+/-}0.08 Dice similarity coefficient based on 150 experimental measurements using an elliptical container, which is suitable for brain injury localization.

biophysics↗

bioRxiv2021

MetaTrass: High-quality Metagenomic Taxonomic Read Assembly of Single-Species based on co-barcoding sequencing data and references

With the development of sequencing technologies and computational analysis in metagenomics, the genetic diversity of non-conserved regions has been receiving intensive attention to unravel the human gut microbial community. However, it remains a challenge to obtain enough microbial draft genomes at a high resolution from a single sample. In this work, we presented MetaTrass with a strategy of binning first and assembling later to assemble high-quality draft genomes based on metagenomics co-barcoding reads and the public reference genomes. We applied the tool to the single tube long fragment reads datasets for four human faecal samples, and generated more high-quality draft genomes with longer contiguity and higher resolution than the common combination strategies of genome assembling and binning. A total of 178 high-quality genomes was successfully assembled by MetaTrass, but the maximum of 58 was generated by the optimal common combination strategy in our tests. These high-quality genomes paved the way for genetic diversity and lineage analysis among different samples. With the high capability of assembling high-quality genomes of metagenomics datasets, MetaTrass will facilitate the study of spatial characters and dynamics of complex microbial communities at high resolution. The open-source code of MetaTrass is available at https://github.com/BGI-Qingdao/MetaTrass.

bioinformatics↗