156 research outputs found

    Sequencing and comparative genomics of Leptospira interrogans serovar pomona and Leptospira kirschneri serovar grippotyphosa.

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    Virulence genes that include methyl-accepting chemotaxis protein, flagellar basal body-associated protein, flagellar motor switch protein, Lig A protein, thermolysin, multiple antibiotic resistance protein, acriflavine resistance protein, and rfb-related genes were identified and compared among the four Leptospira species: pomona, grippotyphosa, lai, and copenhageni. Based on the unique distribution of their virulence genes, grippotyphosa and pomona can be paired while copenhageni and lai similarly can be grouped. This pairing correlates well with their respective host ranges.The ∼ 4.7Mb genomes of Leptospira interrogans serovar pomona and Leptosrira kirschneri serovar grippotyphosa respectively were sequenced to understand the molecular basis of leptospiral physiology, virulence, and pathogenesis in leptospirosis.Nearly 50 metabolic pathways, including glycolysis, pentose phosphate, TCA cycle, oxidative phosphorylation, and ATP synthesis, have been reconstructed for four Leptospira species using KEGG. Domain analysis, isozymes search, and literatures mining confirmed that all these pathways investigated were identical in L. pomona, grippotyphosa, lai, and copenhageni.3,733 genes were predicted in L. pomona and 3,828 genes were predicted in L. grippotyphosa and compared with those of L. lai and copenhageni. The large chromosomes of L. pomona, grippotyphosa, lai, and copenhageni encode 133, 205, 854, and 98 species specific genes, respectively while 77, 99, and 66 genes are species specific in the small chromosomes of L. pomona, grippotyphosa, and lai, respectively, but none are specific in the copenhageni small chromosome

    sPortfolio: Stratified Visual Analysis of Stock Portfolios

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    Quantitative Investment, built on the solid foundation of robust financial theories, is at the center stage in investment industry today. The essence of quantitative investment is the multi-factor model, which explains the relationship between the risk and return of equities. However, the multi-factor model generates enormous quantities of factor data, through which even experienced portfolio managers find it difficult to navigate. This has led to portfolio analysis and factor research being limited by a lack of intuitive visual analytics tools. Previous portfolio visualization systems have mainly focused on the relationship between the portfolio return and stock holdings, which is insufficient for making actionable insights or understanding market trends. In this paper, we present sPortfolio, which, to the best of our knowledge, is the first visualization that attempts to explore the factor investment area. In particular, sPortfolio provides a holistic overview of the factor data and aims to facilitate the analysis at three different levels: a Risk-Factor level, for a general market situation analysis; a Multiple-Portfolio level, for understanding the portfolio strategies; and a Single-Portfolio level, for investigating detailed operations. The system's effectiveness and usability are demonstrated through three case studies. The system has passed its pilot study and is soon to be deployed in industry

    Multi-level characteristics recognition of cancer core therapeutic targets and drug screening for a broader patient population

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    Introduction: Target therapy for cancer cell mutation has brought attention to several challenges in clinical applications, including limited therapeutic targets, less patient benefits, and susceptibility to acquired due to their clear biological mechanisms and high specificity in targeting cancers with specific mutations. However, the identification of truly lethal synthetic lethal therapeutic targets for cancer cells remains uncommon, primarily due to compensatory mechanisms.Methods: In our pursuit of core therapeutic targets (CTTs) that exhibit extensive synthetic lethality in cancer and the corresponding potential drugs, we have developed a machine-learning model that utilizes multiple levels and dimensions of cancer characterization. This is achieved through the consideration of the transcriptional and post-transcriptional regulation of cancer-specific genes and the construction of a model that integrates statistics and machine learning. The model incorporates statistics such as Wilcoxon and Pearson, as well as random forest. Through WGCNA and network analysis, we identify hub genes in the SL network that serve as CTTs. Additionally, we establish regulatory networks for non-coding RNA (ncRNA) and drug-target interactions.Results: Our model has uncovered 7277 potential SL interactions, while WGCNA has identified 13 gene modules. Through network analysis, we have identified 30 CTTs with the highest degree in these modules. Based on these CTTs, we have constructed networks for ncRNA regulation and drug targets. Furthermore, by applying the same process to lung cancer and renal cell carcinoma, we have identified corresponding CTTs and potential therapeutic drugs. We have also analyzed common therapeutic targets among all three cancers.Discussion: The results of our study have broad applicability across various dimensions and histological data, as our model identifies potential therapeutic targets by learning multidimensional complex features from known synthetic lethal gene pairs. The incorporation of statistical screening and network analysis further enhances the confidence in these potential targets. Our approach provides novel theoretical insights and methodological support for the identification of CTTs and drugs in diverse types of cancer

    The Influence of Education and Scientific Research System on China's Science and Technology Innovation Capability

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    This article outlines their impact on China's technological innovation capabilities from nine aspects including primary and secondary education to university education, the shortcomings of scientific research evaluation system, the forward-looking of educational investment and the rationality of research funding, the negative feedback of the employment market on innovative research, intellectual property protection and incentive mechanism, The basic social system and its incentive mechanism combined with learning and research, the incentive mechanism and cultural atmosphere of enterprises and administrative institutions, and the origin of China's modern education model. The comprehensive analysis shows that changing the status quo of China's lack of innovation is a systematic project. A single ministry cannot complete many specific measures of reform, and must have a national-level top-level design. Through reform, the education and scientific research system has reasonable design and strong self-repairing ability. It is the need of innovation to promote industrial upgrading. Its effectiveness directly determines whether China can cross the middle income trap and the great rejuvenation of the Chinese nation

    Targeted RNAseq assay incorporating unique molecular identifiers for improved quantification of gene expression signatures and transcribed mutation fraction in fixed tumor samples.

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    BACKGROUND: Our objective was to assess whether modifications to a customized targeted RNA sequencing (RNAseq) assay to include unique molecular identifiers (UMIs) that collapse read counts to their source mRNA counts would improve quantification of transcripts from formalin-fixed paraffin-embedded (FFPE) tumor tissue samples. The assay (SET4) includes signatures that measure hormone receptor and PI3-kinase related transcriptional activity (SET METHODS: Modifications included steps to introduce eight nucleotides-long UMIs during reverse transcription (RT) in bulk solution, followed by polymerase chain reaction (PCR) of labeled cDNA in droplets, with optimization of the polymerase enzyme and reaction conditions. We used Lin\u27s concordance correlation coefficient (CCC) to measure concordance, including precision (Rho) and accuracy (Bias), and nonparametric tests (Wilcoxon, Levene\u27s) to compare the modified (NEW) SET4 assay to the original (OLD) SET4 assay and to whole transcriptome RNAseq using RNA from matched fresh frozen (FF) and FFPE samples from 12 primary breast cancers. RESULTS: The modified (NEW) SET4 assay measured single transcripts (p\u3c 0.001) and SET CONCLUSIONS: Modifications to the targeted RNAseq protocol for SET4 assay significantly increased the precision of UMI-based and reads-based measurements of individual transcripts, multi-gene signatures, and mutant transcript fraction, particularly with FFPE samples

    A general strategy for synthesis of metal oxide nanoparticles attached on carbon nanomaterials

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    We report a general strategy for synthesis of a large variety of metal oxide nanoparticles on different carbon nanomaterials (CNMs), including single-walled carbon nanotubes, multi-walled carbon nanotubes, and a few-layer graphene. The approach was based on the π-π interaction between CNMs and modified aromatic organic ligands, which acted as bridges connecting metal ions and CNMs. Our methods can be applicable for a large variety of metal ions, thus offering a great potential application

    Evolutionary History of Chemosensory-Related Gene Families across the Arthropoda

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    Chemosensory-related gene (CRG) families have been studied extensively in insects, but their evolutionary history across the Arthropoda had remained relatively unexplored. Here, we address current hypotheses and prior conclusions on CRG family evolution using a more comprehensive data set. In particular, odorant receptors were hypothesized to have proliferated during terrestrial colonization by insects (hexapods), but their association with other pancrustacean clades and with independent terrestrial colonizations in other arthropod subphyla have been unclear. We also examine hypotheses on which arthropod CRG family is most ancient. Thus, we reconstructed phylogenies of CRGs, including those from new arthropod genomes and transcriptomes, and mapped CRG gains and losses across arthropod lineages. Our analysis was strengthened by including crustaceans, especially copepods, which reside outside the hexapod/branchiopod clade within the subphylum Pancrustacea. We generated the first high-resolution genome sequence of the copepod Eurytemora affinis and annotated its CRGs. We found odorant receptors and odorant binding proteins present only in hexapods (insects) and absent from all other arthropod lineages, indicating that they are not universal adaptations to land. Gustatory receptors likely represent the oldest chemosensory receptors among CRGs, dating back to the Placozoa. We also clarified and confirmed the evolutionary history of antennal ionotropic receptors across the Arthropoda. All antennal ionotropic receptors in E. affinis were expressed more highly in males than in females, suggestive of an association with male mate-recognition behavior. This study is the most comprehensive comparative analysis to date of CRG family evolution across the largest and most speciose metazoan phylum Arthropoda

    Gene content evolution in the arthropods

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    Arthropods comprise the largest and most diverse phylum on Earth and play vital roles in nearly every ecosystem. Their diversity stems in part from variations on a conserved body plan, resulting from and recorded in adaptive changes in the genome. Dissection of the genomic record of sequence change enables broad questions regarding genome evolution to be addressed, even across hyper-diverse taxa within arthropods. Using 76 whole genome sequences representing 21 orders spanning more than 500 million years of arthropod evolution, we document changes in gene and protein domain content and provide temporal and phylogenetic context for interpreting these innovations. We identify many novel gene families that arose early in the evolution of arthropods and during the diversification of insects into modern orders. We reveal unexpected variation in patterns of DNA methylation across arthropods and examples of gene family and protein domain evolution coincident with the appearance of notable phenotypic and physiological adaptations such as flight, metamorphosis, sociality, and chemoperception. These analyses demonstrate how large-scale comparative genomics can provide broad new insights into the genotype to phenotype map and generate testable hypotheses about the evolution of animal diversity
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