Biology subjects

Xu, Y.

Publications and source records attributed to Xu, Y..

At least 937 records · Page 52Linked to original sources

bioRxiv2019

The mineralization characteristics of organic carbon and particle composition analysis in reconstructed soil with different proportions of soft rock and sand

The organic carbon mineralization process can reflect the release intensity of soil CO2. Therefore, the study of organic carbon mineralization and particle composition analysis of soft rock and sand compound soil can provide technical support and theoretical basis for the theory of soil organic reconstruction. Based on the previous research, this paper mainly selected four typical treatments of 0:1 (CK), 1:5 (C1), 1:2 (C2) and 1:1 (C3), respectively, and analyzed the soil organic carbon mineralization process and particle composition by lye absorption method, laser particle size meter and scanning electron microscope. The results showed that there was no significant difference in organic carbon content between C1, C2 and C3 treatments, but they were significantly higher than CK treatment (P < 0.05). The organic carbon mineralization rate of each treatment accords with a logarithmic function throughout the culture period (P < 0.01), which can be divided into a rapid decline phase of 1-11 days and a steady decline phase of 11-30 days. The cumulative mineralization amount on the 11th day reached 54.96%-74.44% of the total mineralization amount. At the end of the culture, the cumulative mineralization and potential mineralizable organic carbon content of C1 and C2 treatments were significantly higher than those of CK treatment, and the cumulative mineralization rate was also the lowest with C1 and C2 treatment. The turnover rate constant of soil organic carbon in each treatment was significantly lower than that of CK treatment, and the residence time increased. With the increase of volume fraction of soft rock, the content of silt and clay particles increases gradually, the texture of soil changes from sandy soil to sandy loam, loam and silty loam, and because of the increase of small particles, the structure of soil appears to collapse when the volume ratio of soft rock was 50%. In summary, the ratio of soft rock to sand volume was 1:5-1: 2, which can effectively increased the accumulation of soil organic carbon. At this time, the distribution of soil particles was more uniform, the soil structure was stable, and the mineralization level of unit organic carbon was lower. The research results have practical significance for the large area popularization of soft rock and sand compound technology.

ecology↗

bioRxiv2019

CNOT1 mediates phosphorylation via Protein kinase A on the circadian clock

At the core of the mammalian circadian feedback loop, CLOCK (NPAS2)-BMAL1 is the positive element to activate transcription of downstream genes encoding the negative elements PERs and CRYs. Here we show that CNOT1 associates with both CLOCK and BMAL1, promotes their phosphorylation and increases their protein stability, and in turn inhibits the transcriptional activity of CLOCK-BMAL1. Expression of either CLOCK, BMAL1 or CNOT1 could interact with endogenous Protein Kinase A (PKA) as assessed by co-immunoprecipitation (Co-IP) and kinase assays. PKA could phosphorylate CLOCK and BMAL1 and this was promoted by CNOT1. Genetic deletion of PKA-C by CRISPR-Cas9 results in a longer period of the circadian rhythm; while overexpression of PKA-C induces a shorter period. Furthermore, we demonstrate that CNOT1 associates with CLOCK and BMAL1 in the mouse liver and promotes their phosphorylation. PER2, but not CRY2, is also a PKA target. Our results suggest that CNOT1 and PKA play a critical role in the mammalian circadian clock, revealing a conserved function in eukaryotic circadian regulations.

developmental biology↗

bioRxiv2019

Phanerochaete chrysosporium strain B-22, a parasitic fungus infecting Meloidogyne incognita

We characterized the parasitism by strain B-22 of Phanerochaete chrysosporium on the eggs, second stage juveniles (J2), and adult females of the root-knot nematode (Meloidogyne Incognita). Strain B-22 had a strong lethal effect against M. incognita J2. The highest corrected mortality was 71.9% at 3 x 108 conidia mL-1. The estimated LC50 value was 0.96 x 108 conidia mL-1. Strain B-22 parasitized M. incognita eggs 2 days after treatment, causing the depression and dissolution of egg shells. The fungal spores parasitized J2 by gathering in the body wall, germinating to develop hyphae, and crossing the juvenile cuticle to dissolve it, thereby causing the shrinkage and deformation of the juvenile body wall. The spores and hyphae also attacked adult females, causing the shrinkage and dissolution of their bodies and leakage of contents in 5 days. Results of greenhouse experiments showed that different concentrations of P. chrysosporium effectively controlled different life stages of M. incognita and root knot symptoms in tomato plants. Moreover, the control efficacy increased with increasing conidial concentration; the best results were achieved with 3 x 108 cfu mL-1. In the roots, the highest inhibition rate was 84.61% for adult females, 78.91% for juveniles, 84.25% for the egg mass, and 79.48% for the gall index. The highest juvenile inhibition rate was 89.18% in the soil. Meanwhile, strain B-22 improved the plant growth. Thus, P. chrysosporium strain B-22 is safe for tomato plants while effectively parasitizing M. incognita, making it a promising biocontrol agent against M. incognita.

pathology↗

bioRxiv2019

Multilayered N-glycoproteomics reveals impaired N-glycosylation promoting Alzheimer’s disease

Alzheimers disease (AD) is one of the most common neurodegenerative diseases that currently lacks clear pathogenesis and effective treatment. Protein glycosylation is ubiquitous in brain tissue and site-specific analysis of N-glycoproteome, which is technically challenging, can advance our understanding of the glycoproteins role in AD. In this study, we profiled the multilayered variations in proteins, N-glycosites, N-glycans, and in particular site-specific N-glycopeptides in the APP/PS1 and wild type mouse brain through combining pGlyco 2.0 strategy with other quantitative N-glycoproteomic strategies. The comprehensive brain N-glycoproteome landscape was constructed, and rich details of the heterogeneous site-specific protein N-glycosylations were exhibited. Quantitative analyses explored generally downregulated N-glycosylation involving proteins such as glutamate receptors, as well as fucosylated and oligo-mannose type glycans in APP/PS1 mice versus wild type mice. Moreover, our preliminary functional study revealed that N-glycosylation was crucial for the membrane localization of NCAM1 and for maintaining the excitability and viability of neuron cells. Our work offered a panoramic view of the N-glycoproteomes in Alzheimers disease and revealed that generally impaired N-glycosylation promotes Alzheimers disease progression.

systems biology↗

bioRxiv2019

Meiosis related cancer-testis genes correlate with tumor aneuploidy and immune infiltration in 21 cancer types

The meiosis stage of spermatogenesis and the aneuploidy generation in tumorigenesis are highly linked. Cancer-testis genes (CT genes) were specifically expressed in testis and cancers and may serve as the molecular basis of the shared features between spermatogenesis and tumorigenesis. In the present study, we integrated multi-omics data from bulk samples and cell lines, and single cell RNA-Seq data from testis and two tumors to systematically investigate the association between CT genes and aneuploidy. After ranking genes according to their association with aneuploidy level, we found that CT genes, especially CT genes specifically expressed in meiosis, showed a consistently positive correlation with aneuploidy and homologous recombination deficiency (HRD) level. Similar results were also found in the CT non-coding genes. Then, we constructed a regulatory network based on the single cell RNA-seq data and revealed that the gain of accelerator transcriptional factors (TFs) E2F7 and E2F8 and the loss of the stabilizer TFs RFX2 and NFYA aberrantly activated CT genes in the cancers and were associated with the increase of HRD level. Finally, we found that the association between CT genes and cytotoxic infiltrating lymphocytes can be influenced by the HRD level. In sum, our results revealed the evidence of pseudomeiotic functions of CT genes in the aneuploidy generation process in the cancer cells. The results may help illuminate the origin of aneuploidy in cancers and guide future immunotherapy targeting CT antigens.

genomics↗

bioRxiv2019

Human Chrysomya bezziana myiasis: A systematic review

BackgroundMyiasis due to Old World screw-worm fly, Chrysomya bezziana, is an important obligate zoonotic disease in the OIE-list of diseases and is found throughout much of Africa, the Indian subcontinent, southeast and east Asia. C. bezziana myiases cause not only morbidity and death to animals and humans, but also economic losses in the livestock industries. Because of the aggressive and destructive nature of this disease in hosts, we initiated this study to provide a comprehensive understanding of human myiasis caused by C. bezziana.\n\nMethodsWe conducted a systematic search of the databases in English (PubMed, Embase and African Index Medicus) and Chinese (CNKI, Wanfang, and Duxiu), and international government online reports to 6th February, 2019, to identify studies concerning Chrysomya bezziana. Another ten human cases in China and Papua New Guinea that our team had recorded were also included.\n\nResultsWe retrieved 1,048 reports from which 202 studies were ultimately eligible for inclusion in the present descriptive analyses. Since the first human case due to C. bezziana was reported in 1909, we have summarized 291 cases and found that these cases often occurred in poor hygiene, low socio-economic conditions, old age, and underlying diseases including infections, age-related diseases, and noninfectious chronic diseases. But C. bezziana myiasis appears largely neglected as a serious medical or veterinary condition, with human and animal cases only reported in 16 and 24 countries respectively, despite this fly species recorded as present in 44 countries worldwide.\n\nConclusionOur findings indicate that cryptic myiasis cases due to the obligate parasite, C. bezziana, are under-recognized. Through this in-depth study to clarify the knowledge of human C. bezziana myiasis including its etiology, clinical features, diagnosis, treatment, epidemiology, prevention and control, we call for more vigilance and awareness of the disease from governments, health authorities, clinicians, veterinary workers, nursing homes, and also the general public.\n\nAuthor summaryChrysomya bezziana larvae are characterized by feeding aggressively on the living tissues and body fluids of the host. The nightmare-like feelings of patients suffering from this myiasis, severe tissues and bones destruction, even death, and enormous economic loss in the livestock industries have been described in the previous reports. But our findings indicate that C. bezziana myiases still appear to be under-recognized as a serious medical or veterinary condition throughout the world. Both in China and the world at large, it is probable that C. bezziana distribution could be greater than currently reported. For the first time, we have therefore systematically investigated human myiasis caused by C. bezziana. Our study provides an opportunity for clinicians and health authorities to gain a better understanding of this disease from its etiology, pathology, clinical features, diagnosis, treatment, epidemiology, prevention and control. In addition, our findings will hopefully engage governments, health staff, veterinary workers, the elderly homes, and also the general public in efforts to recognize, prevent and control such infestations.

epidemiology↗

bioRxiv2019

The Complete Chloroplast Genome of Tetraselmis desikacharyi (Chlorodendrophyceae) and Phylogenetic Analysis

Tetraselmis desikacharyi is a marine alga, known as an important plankton for aquaculture as a feed organism. However, the genomic study on this class is rare. Here, we present a complete Chlorodendrophyceae chloroplast genome of T. desikacharyi, belonging to Chlorodendrophyceae with a full length of 149,934bp, characterized by a very small single-copy (SSC) region without any genes and a large inverted repeat (IR) region. A maximum-likelihood (ML) phylogenetic analysis was performed using three kinds of data comprising 50 protein-coding genes, which placed the Chlorodendrophyceae as a deep-diverging lineage of the core Chlorophyta.\n\nT. desikacharyi, characterized by their intense green colored chloroplast, is important for aquaculture as a feed organism, and for studying plankton growth cycles due to their fast growth rate (Arora et al., 2013; Norris et al., 1980). However, only two chloroplast genomes have been published in ...

genomics↗

bioRxiv2019

Allosteric studies of an open pH gate KcsA mutant in its activated and inactivated states

Transmembrane allosteric coupling is a feature of many critical biological signaling events. Here we test whether transmembrane allosteric coupling controls the mean open time of the prototypical potassium channel KcsA in the context of C-type inactivation. Activation of KcsA is initiated by proton binding to the pH gate upon an intracellular drop in pH. Numerous studies have suggested that this proton binding also prompts a conformational switch leading to a loss of affinity for potassium ions at the selectivity filter and therefore to channel inactivation. We tested this mechanism for inactivation using a KcsA mutant (H25R/E118A) that has the pH gate open across a broad range of pH values. We present solid-state NMR measurements of this open mutant at neutral pH to probe the affinity for potassium at the selectivity filter. The potassium binding affinity in the selectivity filter of this mutant, 81 mM, is about 4 orders of magnitude weaker than that of wild type KcsA at neutral pH and is comparable to the value for wild type KcsA at low pH (pH [~] 3.5). This result strongly supports our assertion that the open pH gate allosterically effects the potassium binding affinity of the selectivity filter. In this mutant the protonation state of a glutamate residue (E120) in the pH sensor is sensitive to potassium binding, suggesting that this mutant also has flexibility in the activation gate and is subject to transmembrane allostery.\n\nSignificance statementInactivation of potassium channels controls mean open times and provides exquisite control over biological processes. In the highly conserved C-type inactivation process, opening of the activation gate causes subsequent inactivation. We test whether the open state of the channel simply has a poor ability to bind the K+ ion. Previously, activated and inactivated states were stabilized using truncations or a significant pH drop. Here, we use the H25R/E118A constitutively open mutant of KcsA and also observe a large drop in potassium binding affinity. This provides strong evidence that channel opening causes an allosteric loss of ion affinity, and that the central feature of this universal channel inactivation process is loss of ion affinity at the selectivity filter.

biophysics↗

bioRxiv2019

A direct link between Prss53, hair curvature, and skeletal dysplasia

In humans, protease serine S1 family member 53 (Prss53) is highly expressed in the hair follicle, especially the inner root sheath, which is associated with hair shape according to recent genome-wide association study (GWAS) data. However, no animal evidence has indicated a link between Prss53 and hair shape to date. Here, we used CRISPR/Cas9 to generate Prss53-mutated rabbits. The homozygous (Prss53-/-) rabbits exhibited curved hair and skeletal dyskinesia with severe malformation, while the heterozygous (Prss53+/-) rabbits did not exhibit these features. The curvature features of the hair were accompanied by lesions that were generally denser and less well-defined in the cuticular septation of the hair shaft, and the compartments of the hair follicle were incomplete, as evidenced by decreased expression levels of keratinocyte differentiation genes. In addition, skeletal dysplasia, an increased lethality rate and decreased plasma calcium and serum alkaline phosphatase (ALP) levels were determined in the Prss53-/- rabbits. Furthermore, disrupted calcium metabolism, which may play a role in the hair curvature and skeletal dysplasia of Prss53+/- rabbits, was demonstrated by using high-throughput RNA sequencing data. Thus, our study confirmed for the first time that the loss of Prss53 lead to curved hair in animals and provides new insights into the crucial role of Prss53 in calcium metabolism. Author SummaryNo animal evidence has indicated a link between Prss53 and hair shape to date. The Prss53-/- rabbits exhibited curved hair and skeletal dyskinesia. The disrupted calcium metabolism may play a role in the hair curvature and skeletal dysplasia of Prss53+/- rabbits.

genomics↗

bioRxiv2019

Activated thiol Sepharose-based proteomic approach to globally quantify protein oxidation

Reactive oxygen species (ROS) can act as second messengers for various signaling pathways, and abnormal oxidation contributes to multiple diseases, including cancer. Detecting and quantifying protein oxidation is crucial for a detailed understanding of redox signaling. We developed an Activated Thiol Sepharose (ATS)-based proteomic approach (ATSP) to globally quantify protein oxidation. ATSP can enrich for H2O2-sensitive thiol peptides, which are more likely to contain reactive cysteines involved in redox signaling. We applied our approach to analyze hereditary leiomyomatosis and renal cell carcinoma (HLRCC), a type of kidney cancer that harbors fumarate hydratase (FH)-inactivating mutations and has elevated ROS levels. Multiple proteins were oxidized in FH-deficient cells, including many metabolic proteins, such as the M2 isoform of pyruvate kinase (PKM2). Treatment of HLRCC cells with dimethyl fumarate (DMF) or PKM2 activators alter PKM2 oxidation levels. This newly developed redox proteomics method can globally detect oxidation of reactive cysteines and can be employed to analyze multiple physiological and pathological conditions.

biochemistry↗

bioRxiv2019

Systematic Analysis of Metabolic Pathway Distributions of Bacterial Energy Reserves

Metabolism of energy reserves are essential for bacterial functions such as pathogenicity, metabolic adaptation, and environmental persistence, etc. Previous bioinformatics studies have linked gain or loss of energy reserves such as glycogen and polyphosphate (polyP) with host-pathogen interactions and bacterial virulence based on a comparatively small number of bacterial genomes or proteomes. Thus, understanding the distribution patterns of energy reserves metabolism across bacterial species provides a shortcut route to look into bacterial lifestyle and physiology theoretically. So far, five major energy reserves have been identified in bacteria due to their effective capacity to support bacterial persistence under nutrient deprivation conditions, which include wax ester (WE), triacylglycerol (TAG), polyhydroxyalkanoates (PHA), polyphosphate, and glycogen. Although unknown pathways directly involved in energy reserves keep being discovered with the continuous endeavour of molecular microbiologists and it is currently rather clear about the enzymes related with the metabolism of energy reserves, there is a lack of systematic study of the pathway or key enzyme distributions of the five energy reserves in bacteria from an evolutionary point of view. With the fast development of sequencing technology, abundant bacterial proteomes are available in public database now. In this study, we sourced 8214 manually reviewed bacterial reference proteomes from UniProt database and used statistical models to search homologous sequences of key enzymes related with energy reserves. The distribution patterns of the pathways for energy reserves metabolism are visualized in taxonomy-based phylogenetic trees. According to the study, it was revealed that specific pathways and enzymes are associated with certain types of bacterial groups, which provides evolutionary insights into the understanding of their origins and functions. In addition, the study also confirmed that loss of energy reserves is correlated with bacterial genome reduction. Through this analysis, a much clearer picture about energy reserves metabolism in bacteria is present, which could serve a guide for further theoretical and experimental analyses of energy reserves metabolism in bacteria.

microbiology↗

bioRxiv2019

Cellular structure image classification with small targeted training samples

MotivationCell shapes provide crucial biology information on complex tissues. Different cell types often have distinct cell shapes, and collective shape changes usually indicate morphogenetic events and mechanisms. The identification and detection of collective cell shape changes in an extensive collection of 3D time-lapse images of complex tissues is an important step in assaying such mechanisms but is a tedious and time-consuming task. Machine learning provides new opportunities to automatically detect cell shape changes. However, it is challenging to generate sufficient training samples for pattern identification through deep learning because of a limited amount of images and annotations. ResultWe present a deep learning approach with minimal well-annotated training samples and apply it to identify multicellular rosettes from 3D live images of the Caenorhabditis elegans embryo with fluorescently labelled cell membranes. Our strategy is to combine two approaches, namely, feature transfer and generative adversarial networks (GANs), to boost image classification with small training samples. Specifically, we use a GAN framework and conduct an unsupervised training to capture the general characteristics of cell membrane images with 11,250 unlabelled images. We then transfer the structure of the GAN discriminator into a new Alex-style neural network for further learning with several dozen labelled samples. Our experiments showed that with 10-15 well-labelled rosette images and 30-40 randomly selected non-rosette images our approach can identify rosettes with over 80% accuracy and capture over 90% of the model accuracy achieved with a training dataset that is five times larger. We also established a public benchmark dataset for rosette detection. This GAN-based transfer approach can be applied to study other cellular structures with minimal training samples. Contactdwang7@utk.edu, baoz@mskcc.org

bioinformatics↗

bioRxiv2019

Genome-wide epistasis and co-selection study using mutual information

Discovery of polymorphisms under co-selective pressure or epistasis has received considerable recent attention in population genomics. Both statistical modeling of the population level co-variation of alleles across the chromosome and model-free testing of dependencies between pairs of polymorphisms have been shown to successfully uncover patterns of selection in bacterial populations. Here we introduce a model-free method, SpydrPick, whose computational efficiency enables analysis at the scale of pan-genomes of many bacteria. SpydrPick incorporates an efficient correction for population structure, which is demonstrated to maintain a very low rate of false positive findings among those SNP pairs highlighted to deviate significantly from the null hypothesis of neutral co-evolution in simulated data. We also introduce a new type of visualization of the results similar to the Manhattan plots used in genome-wide association studies, which enables rapid exploration of the identified signals of co-evolution. Application of the method to large population genomic data sets of two major human pathogens, Streptococcus pneumoniae and Neisseria meningitidis, revealed both previously identified and novel putative targets of co-selection related to virulence and antibiotic resistance, highlighting the potential of this approach to drive molecular discoveries, even in the absence of phenotypic data.

genomics↗

bioRxiv2019

LncRNA Dnmt3aos regulates Dnmt3a expression leading to aberrant DNA methylation in macrophage polarization

Long non-coding RNAs (lncRNAs) play key roles in various biological processes. However, the roles of lncRNAs in macrophage polarization remain largely unexplored. In this study, thousands of lncRNAs were identified that are differentially expressed in distinct polarized bone marrow-derived macrophages (BMDMs). Among them, Dnmt3aos (DNA methyltransferase 3A, opposite strand), as a known lncRNA, locates on the antisense strand of Dnmt3a. Functional experiments further confirmed that Dnmt3aos were highly expressed in M(IL-4) macrophages and participated in the regulation of Dnmt3a expression, and played a key role in macrophage polarization. The DNA methylation profiles between the Dnmt3aos knockdown group and the control group in M(IL-4) macrophages were determined by MeDIP-seq technique for the first time, and the Dnmt3aos-Dnmt3a axis-mediated DNA methylation modification-regulated macrophage polarization related gene IFN-{gamma} was identified. Our study will help to enrich our knowledge of the mechanism of macrophage polarization and will provide new insights for immunotherapy in macrophage-associated diseases.

cell biology↗

bioRxiv2019

Construction of synthetic microbiota for reproducible flavor metabolism in Chinese light aroma type liquor produced by solid-state fermentation

Natural microbiota plays an essential role in flavor compounds producing for traditional food fermentation. Whereas, the fluctuation of natural microbiota results in the inconstancy of food quality. Thus, it is critical to reveal the core microbiota for flavor compounds producing and construct a synthetic core microbiota for constant food fermentation. Here, we revealed the core microbiota based on their flavor-producing and co-occurrence performance, using Chinese light aroma type liquor as a model system. Five genera were identified to be the core microbiota, including Lactobacillus, Saccharomyces, Pichia, Geotrichum, and Candida. The synthetic core microbiota of these five genera presented a reproducible dynamic profile with that in the natural microbiota. Monte Carlo test showed that the interpretation of five environmental factors (lactic acid, ethanol and acetic acid contents, moisture and pH) on the synthetic microbiota distribution were highly significant (P < 0.01), which was similar with that in the natural fermentation system. In addition, 77.27% of the flavor compounds produced by the synthetic core microbiota showed a similar dynamic profile ({rho} > 0) with that in the natural liquor fermentation process, and the flavor profile presented a similar composition. It indicated that the synthetic core microbiota is efficient for reproducible flavor metabolism. This work established a method for identifying core microbiota and constructing a synthetic microbiota for reproducible flavor compounds. It is of great significance for the tractable and constant production of various fermented foods.\n\nIMPORTANCEThe transformation from natural fermentation to synthetic fermentation is essential to construct a constant food fermentation process, which is the premise for stably making high-quality food. According to the functions of flavor-producing and co-occurring in dominant microbes, we provided a system-level approach to identify the core microbiota in Chinese light aroma type liquor fermentation. In addition, we successfully constructed a synthetic core microbiota to simulate the microbial community succession and flavor compounds production in the in vitro system. The constructed synthetic core microbiota could not only facilitate a mechanistic understanding of the structure and function of the microbiota, but also be beneficial for constructing a tractable and reproducible food fermentation process.

microbiology↗

bioRxiv2018

gencore: an efficient tool to generate consensus reads for error suppressing and duplicate removing of NGS data

BackgroundRemoving duplicates might be considered as a well-resolved problem in next-generation sequencing (NGS) data processing domain. However, as NGS technology gains more recognition in clinical applications (i.e. cancer testing), researchers start to pay more attention to its sequencing errors, and prefer to remove these errors while performing deduplication operations. Recently, a new technology called unique molecular identifier (UMI) has been developed to better identify sequencing reads derived from different DNA fragments. Most existing duplicate removing tools cannot handle the UMI-integrated data. Some modern tools can work with UMIs, but are usually slow and use too much memory, making them not suitable for cloud-based deployment. Furthermore, existing tools rarely report rich statistical results, which are very important for quality control and downstream analysis. These unmet requirements drove us to develop an ultra-fast, simple, little-weighted but powerful tool for duplicate removing and sequence error suppressing, with features of handling UMIs and reporting informative results.\n\nResultsThis paper presents an efficient tool gencore for duplicate removing and sequence error suppressing of NGS data. This tool clusters the mapped sequencing reads and merges reads in each cluster to generate one single consensus read. While the consensus read is generated, the random errors introduced by library construction and sequencing can be removed. This error-suppressing feature makes gencore very suitable for the application of detecting ultra-low frequency mutations from deep sequencing data. When unique molecular identifier (UMI) technology is applied, gencore can use them to identify the reads derived from same original DNA fragment. gencore reports statistical results in both HTML and JSON formats. The HTML format report contains many interactive figures plotting statistical coverage and duplication information. The JSON format report contains all the statistical results, and is interpretable for downstream programs.\n\nConclusionsComparing to the conventional tools like Picard and SAMtools, gencore greatly reduces the output datas mapping mismatches, which are mostly caused by errors. Comparing to some new tools like UMI-Reducer and UMI-tools, gencore runs much faster, uses less memory, generates better consensus reads and provides simpler interfaces. To our best knowledge, gencore is the only duplicate removing tool that generates both informative HTML and JSON reports. This tool is available at: https://github.com/OpenGene/gencore

bioinformatics↗

bioRxiv2018

Nanopore metagenomic sequencing of full length human metapneumovirus (HMPV) within a unique sub-lineage

Human metapneumovirus (HMPV) has been recognized as an important pathogen which can cause a spectrum of respiratory tract disease. Here, we report Nanopore metagenomic sequencing of the first full length HMPV genome directly from a throat swab from a UK patient with complex lung disease and immunocompromise. We found a predominance (26.4%) of HMPV reads in the metagenomic sequencing data and consequently assembled the full genome at a high depth of coverage (mean 4,786). Through phylogenetic analyses, we identified this HMPV strain to originate from a unique genetic group in A2b, showing the presence of this group in the UK. Our study demonstrated the effectiveness of Nanopore metagenomic sequencing for diagnosing infectious diseases and recovering complete sequences for genomic characterization, highlighting the applicability of Nanopore sequencing in clinical settings.\n\nImportanceNanopore metagenomic sequencing has the potential to evolve as a point-of-care test for a range of infectious diseases. Here, we report the first full length human metapneumovirus (HMPV) genome in the UK sequenced by Nanopore from a non-invasive sample from an immunocompromised patient. We demonstrate the presence of HMPV from a unique genetic group not previously reported from the UK. Our study demonstrates the effectiveness of Nanopore sequencing for diagnosing an infection that was not detected by routine first-line tests in the clinical microbiology laboratory. We report sufficient genomic data to provide insight into the epidemiology of infection and with the potential to inform treatment decisions.

microbiology↗

bioRxiv2018

Uncovering the role admixture in health disparity: characterization of hepatocyte gene expression and DNA methylation in African-Americans

BackgroundAfrican Americans (AAs) are an admixed population with portions of their genome derived from West Africans and Europeans. In AAs, the proportion of West African ancestry (WAA) can vary widely and may explain the genetic drivers of disease, specifically those that disproportionately affect this understudied population. To examine the relationship between the proportion of WAA and gene expression, we used high dimensional data obtained from AA primary hepatocytes, a tissue important in disease and drug response. MethodsRNA sequencing (Illumina HiSeq Platform) was conducted on 60 AA-derived primary hepatocytes, with methylation profiling (Illumina MethylationEPIC BeadChip) of 44 overlapping samples. WAA for each sample was calculated using fastSTRUCTURE and correlated to both gene expression and DNA methylation. The GTEx consortium (n = 15) was used for replication and a second cohort (n = 206) was using used for validation using differential gene expression between AAs and European-Americans. ResultsWe identified 131 genes associated with WAA (FDR< 0.1), of which 28 gene expression traits were replicated (FDR<0.1) and enriched in angiogenesis and inflammatory pathways (FDR<0.1). These 28 replicated gene expression traits represented 257 GWAS catalog phenotypes. Among the PharmGKB pharmacogenes, VDR, PTGIS, ALDH1A1, CYP2C19 and P2RY1 were associated with WAA (p < 0.05) with replication of CYP2C19 and VDR in GTEx. Association of DNA methylation with WAA identified 1037 differentially methylated regions (FDR<0.05), with hypomethylated genes enriched in drug response pathways. Overlapping of differentially methylated regions with the 131 significantly correlated gene expression traits identified 5 genes with concordant directions of effect: COL26A1, HIC1, MKNK2, RNF135, SNAI1 and TRIM39. ConclusionsWe conclude that WAA contributes to variability in hepatic gene expression and DNA methylation with identified genes indicative of diseases disproportionately affecting AAs. Specifically, WAA-associated genes were linked to previously identified loci in cardiovascular disease (PTGIS, PLAT), renal disease (APOL1) and drug response (CYP2C19).

genomics↗