Biology subjects

Yang, Y.

Publications and source records attributed to Yang, Y..

At least 1,279 records · Page 71Linked to original sources

bioRxiv2019

A chromosome-level genome assembly for the beet armyworm (Spodoptera exigua) using PacBio and Hi-C sequencing

BackgroundThe beet armyworm, Spodoptera exigua (Hubner), is a worldwide, polyphagous agricultural pest feeding on vegetable, field, and flower crops. However, the lack of genome information on this insect severely limits our understanding of its rapid adaptation and hampers the development of efficient pest management strategies. FindingsWe report a chromosome-level genome assembly using single-molecule real-time PacBio sequencing and Hi-C data. The final genome assembly was 446.80 Mb with a scaffold N50 of 14.36 Mb, and captured 97.9% complete arthropod Benchmarking Universal Single-Copy Orthologs (BUSCO, n=1,658). A total of 367 contigs were anchored to 32 pseudo-chromosomes, covering 96.18% (429.74 Mb) of the total genome length. We predicted 17,727 protein-coding genes, of which 81.60% were supported by transcriptome evidence and 96.47% matched UniProt protein records. We also identified 867,102 (147.97 Mb/33.12%) repetitive elements and 1,609 noncoding RNAs. Synteny inference indicated a conserved collinearity between three lepidopteran species. Gene family evolution and function enrichment analyses showed the significant expansions in families related to development, dietary, detoxification and chemosensory system, indicating these families may play a role in host plant specialization and niche adaptation. ConclusionsWe have generated a high-quality chromosomal-level genome that could provide a valuable resource for a better understanding and management of the beet armyworm.

genomics↗

bioRxiv2019

Longitudinal epi-transcriptome profiling reveals the crucial role of m6A in prenatal skeletal muscle development of pigs

BackgroundN6-methyladenosine (m6A) is the most abundant RNA modification and essentially participates in the regulation of skeletal muscle development. However, the status and function of m6A methylation in prenatal myogenesis remains unclear now. ResultsIn our present study, we first demonstrate that chemical suppression of m6A and knockdown METTL14 significantly inhibit the differentiation and promote the proliferation of C2C12 myoblast cells. The mRNA expression of m6A reader protein IGF2BP1, which functions to promote the stability of target mRNA, continually decreases during the prenatal skeletal muscle development. Thereafter, profiling transcriptome-wide m6A for six developmental stage of prenatal skeletal muscle, which spanning two important waves of pig myogenesis, were performed using a refined MeRIP sequencing technology that is optimal for small-amount of RNA samples. Highly dynamic m6A methylomes across different development stages were then revealed, with majority of the affected genes enriched in pathways of skeletal muscle development. In association with the transcriptome-wide alterations, transcriptional regulatory factors (MyoD) and differentiated markers (MyHC, MYH1) of muscle development are simultaneously regulated with m6A and IGF2BP1. Knockdown of IGF2BP1 also suppresses myotube formation and promotes cell proliferation. ConclusionsThe present study clarifies the dynamics of RNA m6A methylation in the regulation of prenatal skeletal muscle development, providing a data baseline for future developmental as well as biomedical studies of m6A functions in muscle development and disease.

genetics↗

bioRxiv2019

QTL Mapping and integration as well as candidate gene prediction for branch number in soybean

Branch number is an important factor that affects crop plant architecture and yield in soybean. With the aim of elucidating the genetic basis of branch number, we identified 10 consensus quantitative trait loci (QTLs) through preliminary mapping, which were on chromosome A1, B2, C1, C2, D1a, D1b, F, L and N, explained 0.3-33.3% of the phenotypic variance. Of these, three QTLs were identical to previously identified ones, whereas the other seven were novel. In addition, one major QTL-qBN.C2 (R2=33.3%) was detected in all three environments and another new major QTL-qBN.N (R2=19.6%) was detected in two environments (Taiyuan 2017 and Taiyuan 2018), but only in Taiyuan. Thus, the QTL x environment interaction analysis confirmed that QTL-qBN.N was strongly affected by the environment. We compared the physical positions of the QTL intervals of the candidate genes potentially involved in branching development, and five orthologous genes were ultimately selected and related to the establishment of axillae meristem organization and lateral organs, qBN.A1 (SoyZH13_05G177000.m1), qBN.C2 (SoyZH13_06G176500.m1, SoyZH13_06G185600.m1), and qBN.D1b-1 (SoyZH13_02G035400.m1, SoyZH13_02G070000.m3). The results of our study reveal a complex and relatively complete genetic architecture and can serve as a basis for the positional gene cloning of branch number in soybean.

genetics↗

bioRxiv2019

Molecular basis of differential parasitism between non-encapsulated and encapsulated Trichinella revealed by a high-quality genome assembly

Understanding roles of repetitive sequences in genomes of parasites could offer insights into their evolution, speciation, and parasitism. As a unique intracellular nematode, Trichinella consists of two clades, encapsulated and non-encapsulated. Genomic correlation to the distinct differences between the two clades is still unclear. Here we report an annotated draft reference genome of non-encapsulated Trichinella, T. pseudospiralis, and performed comparative analyses with encapsulated T. spiralis. Genome analysis revealed that, during Trichinella evolution, repetitive sequence insertions played an important role in gene family expansion in synergy with DNA methylation, especially for the DNase II members of the phospholipase D superfamily and Glutathione S-transferases. We further identify the genomic and epigenomic regulation of excretory/secretory products in relation to differences in parasitism, pathology and immunology between the two clades Trichinella. The present study provided a foundation for further elucidation of mechanism of nurse cell formation and immunoevasion as well as identification of phamarcological and diagnostic targets of trichinellosis.

genomics↗

bioRxiv2019

Recombinant HcGAPDH Protein Expressed on Probiotic Bacillus subtilis Spores Protects Sheep from Haemonchus contortus Infection by Inducing both Humoral and Cell-mediated Responses

Probiotic Bacillales have been shown effective in controlling pathogens. In particular, live probiotic bacteria are thought to improve the composition of gastrointestinal microbiota, and to reduce pathogen colonization. However, how probiotics regulate immune responses and protect the host from parasitic infection remains largely unknown. In this study, we investigated whether Bacillales can be used against Haemonchus contortus, a parasitic nematode that infects small ruminants in sheep and goats worldwide. Using 16S ribosomal RNA sequencing, we found that Bacillales was highly depleted in the abomasal microbiota of sheep infected with H. contortus. We constructed a recombinant Bacillus subtilis strain (rBSCotB-HcG) that express glyceraldehyde-3-phosphate dehydrogenase of H. contortus (HcGAPDH) on its spore surface. However, mice orally administrated with the rBSCotB-HcG strain showed strong Th1-dominated immune responses; and sheep administrated per os with rBSCotB-HcG showed increased proliferation of peripheral blood mononuclear cells, elevated anti-HcGAPDH IgG levels in sera, and higher anti-HcGAPDH sIgA levels in intestinal mucus. In addition, treatment of H. contortus infected sheep with rBSCotB-HcG (Hc+rBSCotB-HcG) promoted the abundance of probiotic species in the abomasal microbiota; it also improved the average weight gain of the sheep by 27.7%. These Hc+rBSCotB-HcG sheep have reduced number of eggs per gram of feces (by 84.1%) and worm burdens (by 71.5%), with alleviated abomasal damage by H. contortus. Collectively, our data demonstrate the protective roles of CotB-HcGAPDH-expressing B. subtilis spores against H. contortus infection, suggesting a potential value of using this probiotic-based strategy in controlling parasitic nematodes of socioeconomic importance. ImportanceSequencing of the infected sheep s stomach flora revealed potential probiotics that could control H. contortus infection, and further genetically engineered recombinant probiotic spores expressing parasite protein, and validated their good immunogenicity in a mouse model. In the sheep infection model, the recombinant probiotics have proven to be effective against parasite infections.

microbiology↗

bioRxiv2019

Epiviz File Server: Query, Transform and Interactively Explore Data from Indexed Genomic Files

Genomic data repositories like The Cancer Genome Atlas (TCGA), Encyclopedia of DNA Elements (ENCODE), Bioconductors AnnotationHub and ExperimentHub etc., provide public access to large amounts of genomic data as flat files. Researchers often download a subset of files data from these repositories to perform their data analysis. As these data repositories become larger, researchers often face bottlenecks in their exploratory data analysis. Based on the concepts of a NoDB paradigm, we developed epivizFileServer, a Python library that implements an in-situ data query system for local or remotely hosted indexed genomic files, not only for visualization but also data manipulation. The File Server library decouples data from analysis workflows and provides an abstract interface to define computations independent of the location, format or structure of the file.

bioinformatics↗

bioRxiv2019

Highly diverse Asgard archaea participate in organic matter degradation in coastal sediments

Asgard is an archaeal superphylum that might hold the key to understand the origin of eukaryotes, but its diversity and ecological roles remain poorly understood. Here, we reconstructed 15 metagenomic-assembled genomes (MAGs) from coastal sediments covering most known Asgard archaea and a novel group, which is proposed as a new Asgard phylum named as the "Gerdarchaeota". Genomic analyses predict that Gerdarchaeota are facultative anaerobes in utilizing both organic and inorganic carbon. Unlike their closest relatives Heimdallarchaeota, Gerdarchaeota have genes encoding for cellulase and enzymes involving in the tetrahydromethanopterin-based Wood-Ljungdahl pathway. Transcriptomic evidence showed that all known Asgard archaea are capable of degrading organic matter, including peptides, amino acids and fatty acids, in different ecological niches in sediments. Overall, this study broadens the diversity of the mysterious Asgard archaea and provides evidence for their ecological roles in coastal sediments.

microbiology↗

bioRxiv2019

hFUT1-based live cell assay to profile α1-2-fucosides enhanced influenza A virus infection

Host cell-surface glycans play critical roles in influenza A virus (IAV) infection ranging from modulation of IAV attachment to membrane fusion and host tropism. Approaches for quick and sensitive profiling of the viral avidity towards a specific type of host-cell glycan can contribute to the understanding of tropism switching among different strains of IAV. In this study, we developed a method based on chemoenzymatic glycan engineering to investigate the possible involvement of 1-2-fucosides in IAV infections. Using a truncated human fucosyltransferase 1 (hFuT1), we were able to create 1-2-linked fucosides in situ on the host cell surface to assess their influence on the host cell binding to IAV hemagglutinin and the susceptibility of host cells toward IAV induced killing. We discovered that the newly added 1-2-fucosides on host cells enhanced the infection of several human pandemic IVA subtypes. These findings suggest that glycan epitopes other than sialic aicds should be taken into consideration for assessing the human pandemic risk of this viral pathogen.

biochemistry↗

bioRxiv2019

Molecular mechanisms behind global distribution of earthworm revealed by the genome

Earthworms (Annelida: Crassiclitellata), are widely distributed around the world due to their great adaptability. However, lack of a high-quality genome sequence prevents gaining the many insights into physiology, phylogeny, and genome evolution that could come from a good earthworm genome. Herein, we report a complete genome assembly of the earthworm Amynthas corticis of about 1.2 Gb, based on a strategy combining third-generation long-read sequencing and Hi-C mapping. A total of 29,256 protein-coding genes are annotated in this genome. Analysis of resequencing data indicates that this earthworm is a triploid species. Furthermore, gene family evolution analysis shows that comprehensive expansion of gene families in the earthworm genome has produced more defensive functions compared with other species in Annelida. Quantitative proteomic iTRAQ analysis shows 97 immune related proteins and 16S rDNA sequences shows 88 microbes with significantly response to pathogenic Escherichia coli O157:H7. Our genome assembly provides abundant and valuable resources for the earthworm research community, serving as a first step toward uncovering the mysteries of this species, may explain its powerful defensive functions adapt to complex environment and invasion from molecular level.

genomics↗

bioRxiv2019

Transcriptome-wide association analysis of 211 neuroimaging traits identifies new genes for brain structures and yields insights into the gene-level pleiotropy with other complex traits

Structural and microstructural variations of human brain are heritable and highly polygenic traits, with hundreds of associated genes founded in recent genome-wide association studies (GWAS). Using gene expression data, transcriptome-wide association studies (TWAS) can prioritize these GWAS findings and also identify novel gene-trait associations. Here we performed TWAS analysis of 211 structural neuroimaging phenotypes in a discovery-validation analysis of six datasets. Using a cross-tissue approach, TWAS discovered 204 associated genes (86 new) exceeding Bonferroni significance threshold of 1.37*10-8 (adjusted for testing multiple phenotypes) in the UK Biobank (UKB) cohort, and validated 18 TWAS or previous GWAS-detected genes. The TWAS-significant genes of brain structures had been linked to a wide range of complex traits in different domains. Additional TWAS analysis of 11 cognitive and mental health traits detected 69 overlapping significant genes with brain structures, further characterizing the genetic overlaps among these brain-related traits. Through TWAS gene-based polygenic risk scores (PRS) prediction, we found that TWAS PRS gained substantial power in association analysis compared to conventional variant-based PRS, and up to 6.97% of phenotypic variance (p-value=7.56*10-31) in testing datasets can be explained by UKB TWAS-derived PRS. In conclusion, our study illustrates that TWAS can be a powerful supplement to traditional GWAS in imaging genetics studies for gene discovery-validation, genetic co-architecture analysis, and polygenic risk prediction.

genetics↗

bioRxiv2019

Attenuation of epigenetic regulator SMARCA4 and ERK-ETS signaling suppresses aging-related dopaminergic degeneration

Parkinsons disease (PD) is a complex disease with high heterogeneity. How complex interactions of genetic, environmental factors and aging jointly contribute to dopaminergic degeneration in PD is largely unclear. Here, we applied frequent gene co-expression analysis on human patient substantia nigra-specific microarray datasets to identify potential novel disease-related genes. In vivo Drosophila studies validated two of 32 candidate genes, a chromatin remodeling factor SMARCA4 and a biliverdin reductase BLVRA. Inhibition of SMARCA4 was able to prevent dopaminergic degeneration not only caused by overexpression of BLVRA but also in four most common Drosophila PD models. Mechanistically, aberrant SMARCA4 and BLVRA converged on elevated ERK-ETS activity, attenuation of which by either genetic or pharmacological manipulation effectively suppressed dopaminergic degeneration in vivo. Drug inhibition of MEK/ERK also mitigated mitochondrial defects in PD gene-deficient human cells. Our findings underscore the important role of epigenetic regulators and implicate a common signaling axis for therapeutic intervention in a broad range of aging-related disorders including PD.

neuroscience↗

bioRxiv2019

SPOCK1 promotes breast cancer progression via interacting with SIX1 and activating AKT/mTOR signaling pathway

SPOCK1 is highly expressed in many types of cancer, which has been recognized as a promoter of cancer progression, while its regulatory mechanism remains to be clear in breast cancer (BC). This study aimed to explore the precise function of SPOCK1 in BC progression and the mechanism by which SPOCK1 was involved in cell proliferation and epithelial-mesenchymal transition (EMT). Immunohistochemistry (IHC) and database analysis displayed that high expression of SPOCK1 was positively associated with histological grade, lymph node metastasis (LN) and poor clinical prognosis in BC. A series of assays both in vitro and in vivo elucidated that altering SPOCK1 level led to distinctly changes in BC cell proliferation and metastasis. Investigations of potential mechanisms revealed that SPOCK1 interacted with SIX1 could enhance cell proliferation, cell cycle and EMT process by activating the AKT/mTOR pathway, whereas inhibition of AKT/mTOR pathway or depletion of SIX1 reversed the effects of SPOCK1 overexpression. Furthermore, SPOCK1 and SIX1 were highly expressed in BC and might indicate poor prognoses. Altogether, SPOCK1/SIX1 promoted BC progression by activating AKT/mTOR pathway to accelerate cell proliferation and metastasis in BC, and SPOCK1/SIX1 might be promising clinical therapeutic targets to prevent BC progression. IMPORTANCEThe incidence of BC is alarmingly high and many patients initially diagnosed without detectable metastases will eventually develop metastatic lesions. The occurrence of metastasis is responsible for the death of many patients, which also represents a big challenge for researchers to improve the survival rates of BC patients. Hence the scientific community pays more attention on cancer targeted therapy. This research is significant for identifying the underlying mechanisms and capabilities of SPOCK1-induced BC activities, which will greatly apply novel targets and new treatment strategies for clinicians, leading to broader biomedical impacts.

cancer biology↗

bioRxiv2019

The circadian clock and darkness control natural competence in cyanobacteria

Natural genetic competence-based transformation contributed to the evolution of prokaryotes, including the cyanobacterial phylum that established oxygenic photosynthesis. The cyanobacterium Synechococcus elongatus is noted both as a model system for analyzing a prokaryotic circadian clock and for its facile, but poorly understood, natural competence. Here a genome-wide screen aimed at determining the genetic basis of competence in cyanobacteria identified all genes required for natural transformation in S. elongatus, including conserved Type IV pilus, competence-associated, and newly described genes, and revealed that the circadian clock controls the process. The findings uncover a daily program that determines the state of competence in S. elongatus and adapts to seasonal changes of day-length. Pilus biogenesis occurs daily in the morning, but competence is maximal upon the coincidence of circadian dusk and the onset of darkness. As in heterotrophic bacteria, where natural competence is conditionally regulated by nutritional or other stress, cyanobacterial competence is conditional and is tied to the daily cycle set by the cells most critical nutritional source, the Sun.

microbiology↗

bioRxiv2019

Cumulus: a cloud-based data analysis framework for large-scale single-cell and single-nucleus RNA-seq

Massively parallel single-cell and single-nucleus RNA-seq (sc/snRNA-seq) have opened the way to systematic tissue atlases in health and disease, but as the scale of data generation is growing, so does the need for computational pipelines for scaled analysis. Here, we developed Cumulus, a cloud-based framework for analyzing large scale sc/snRNA-seq datasets. Cumulus combines the power of cloud computing with improvements in algorithm implementations to achieve high scalability, low cost, user-friendliness, and integrated support for a comprehensive set of features. We benchmark Cumulus on the Human Cell Atlas Census of Immune Cells dataset of bone marrow cells and show that it substantially improves efficiency over conventional frameworks, while maintaining or improving the quality of results, enabling large-scale studies.

bioinformatics↗

bioRxiv2019

Novel mediation analysis of human plasma proteome and metabolome reveals mediators of improved glycemia after gastric bypass surgery

Molecular mechanisms by which Roux-en-Y gastric bypass (RYGB) improves glycemic control and metabolism in type 2 diabetes (T2D) remain incompletely understood. In the SLIMM-T2D trial, participants with T2D were randomized to RYGB or nonsurgical management and their fasting plasma proteome and metabolome were analyzed for up to 3 years. To identify analytes that mediate improvement in outcomes, we developed a high-throughput mediation analysis method (Hitman), which is significantly more powerful than existing methods. Top-ranking analyte mediators of glycemia improvement were growth hormone receptor and prolylhydroxyproline, which were more significant than any clinical mediator, including BMI. Beta-alanine and Histidine Metabolism (both including CNDP1) were top differentially regulated pathways, and Valine, Leucine and Isoleucine Degradation was also a top differentially-regulated pathway and a top mediator of improvement in insulin resistance. The identified analytes may serve as novel targets for T2D therapy. More broadly, Hitman can identify analyte mediators of outcomes in randomized trials for which high-throughput data are available.

systems biology↗

bioRxiv2019

Plasmodiophora brassicae in its environment-effects of temperature and light on resting spore survival in soil

Clubroot caused by Plasmodiophora brassicae is an important disease on cruciferous crops worldwide. Management of clubroot has been challenging, due largely to the millions of resting spores produced within an infected root that can survive dormant in the soil for many years. This study was conducted to investigate some of the environmental conditions that may affect the survival of resting spores in the soil. Soil samples containing clubroot resting spores (1 x 107 spores g-1 soil) were stored at various temperatures for two years. Additionally, other samples were buried in soil, or kept on the soil surface in the field. The content of P. brassicae DNA and the numbers of viable spores in the samples were assessed by quantitative polymerase chain reaction (qPCR) and pathogenicity bioassays, respectively. The results indicated that 4{degrees}C, 20{degrees}C and being buried in the soil were better conditions for spore survival than were -20{degrees}C, 30{degrees}C and at the soil surface. Most of the spores kept on the soil surface were killed, suggesting the negative effect of light on spore viability. Additional experiments confirmed that ultraviolet (UV) light contributed a large negative effect on spore viability as lower pathogenicity and less DNA content were observed from the 2-and 3-hour UV light treated spores compared to the untreated control. Finally, this work demonstrated that DNA-based quantification methods such as qPCR can be poor predictors of P. brassicae disease potential due to the presence and persistence of DNA from dead spores.

microbiology↗

bioRxiv2019

Evaluation of Commercially Available Exosomal Isolation Kits from Human Plasma

Exosomes are cell-derived lipid bilayer particles which are abundant in biological fluids. Exosome is an emerging source of biomarkers to diagnose various human diseases. Sequencing based exosomal studies could provide a comprehensive view of exosomal RNA and protein. To extracted these inclusions, exosomes should be isolated from the plasma first. Several exosome isolation methods were introduced since the discover of exosome. To promote the clinical application of exosomal inclusions, different isolation methods should be compared. We isolated exosomes from human plasma by using user-friendly and commercially available kits, SBI ExoQuick and QIAGEN exoRNeasy. Subsequently, small RNA sequencing was performed with two groups of isolated exosome samples and one group of plasma samples. No fundamental differences of exRNA yield between SC and EQ were found. In RNA profile analysis, the small RNA aligned reads, miRNA pattern, sample clustering varied as a result of methodological differences. Small RNA isolated by ExoQuick presented better data quality and RNA profile than exoRNeasy. This study compared sRNA sequencing data generated from two exosome isolation kits, it provides a reference for future small RNA studies and biomarker prediction in human plasma exosome.

bioinformatics↗

bioRxiv2019

Imputing missing RNA-seq data from DNA methylation by using transfer learning based-deep neural network

BackgroundGene expression plays a key intermediate role in linking molecular features at DNA level and phenotype. However, due to various limitations in experiments, the RNA-seq data is missing in many samples while there exists high-quality of DNA methylation data. As DNA methylation is an important epigenetic modification to regulate gene expression, it can be used to predict RNA-seq data. For this purpose, many methods have been developed. A common limitation of these methods is that they mainly focus on single cancer dataset, and do not fully utilize information from large pan-cancer dataset. ResultsHere, we have developed a novel method to impute missing gene expression data from DNA methylation data through transfer learning-based neural network, namely TDimpute. In the method, the pan-cancer dataset from The Cancer Genome Atlas (TCGA) was utilized for training a general model, which was then fine-tuned on the specific cancer dataset. By testing on 16 cancer datasets, we found that our method significantly outperforms other state-of-the-art methods in imputation accuracy with 7%-11% increase under different missing rates. The imputed gene expression was further proved to be useful for downstream analyses, including the identification of both methylation-driving and prognosis-related genes, clustering analysis, and survival analysis on the TCGA dataset. More importantly, our method was indicated to be useful for general purpose by the independent test on the Wilms tumor dataset from the Therapeutically Applicable Research To Generate Effective Treatments (TARGET) project. ConclusionsTDimpute is an effective method for RNA-seq imputation with limited training samples.

bioinformatics↗