Warecorcoran0566

9280 and 0.9276 in global leave-one-out cross validation (global LOOCV) and five-fold cross validation (5-CV), respectively, showing that GRL2, 1-NMF can powerfully discover potential disease-related miRNAs, even if there is no known associated disease.BACKGROUND The interactions between non-coding RNAs (ncRNA) and proteins play an essential role in many biological processes. Several high-throughput experimental methods have been applied to detect ncRNA-protein interactions. However, these methods are time-consuming and expensive. Accurate and efficient computational methods can assist and accelerate the study of ncRNA-protein interactions. RESULTS In this work, we develop a stacking ensemble computational framework, RPI-SE, for effectively predicting ncRNA-protein interactions. More specifically, to fully exploit protein and RNA sequence feature, Position Weight Matrix combined with Legendre Moments is applied to obtain protein evolutionary information. Meanwhile, k-mer sparse matrix is employed to extract efficient feature of ncRNA sequences. Finally, an ensemble learning framework integrated different types of base classifier is developed to predict ncRNA-protein interactions using these discriminative features. The accuracy and robustness of RPI-SE was evaluated on three benchmark data sets under five-fold cross-validation and compared with other state-of-the-art methods. CONCLUSIONS The results demonstrate that RPI-SE is competent for ncRNA-protein interactions prediction task with high accuracy and robustness. It's anticipated that this work can provide a computational prediction tool to advance ncRNA-protein interactions related biomedical research.BACKGROUND Taxus cells are a potential sustainable and environment-friendly source of taxol, but they have low survival ratios and slow grow rates. Despite these limitations, Taxus callus cells induced through 6 months of culture contain more taxol than their parent tissues. In this work, we utilized 6-month-old Taxus media calli to investigate their regulatory mechanisms of taxol biosynthesis by applying multiomics technologies. Our results provide insights into the adaptation strategies of T. media by transcriptional reprogramming when induced into calli from parent tissues. RESULTS Seven out of 12 known taxol, most of flavonoid and phenylpropanoid biosynthesis genes were significantly upregulated in callus cells relative to that in the parent tissue, thus indicating that secondary metabolism is significantly strengthened. The expression of genes involved in pathways metabolizing biological materials, such as amino acids and sugars, also dramatically increased because all nutrients are supplied from the medN Our results suggest that increasing the biosynthesis of taxol and other secondary metabolites is an active regulatory measure of calli to adapt to heterotrophic culture, and this alteration mainly involved direct and indirect miRNA-induced transcriptional reprogramming. These results expand our understanding of the relationships among the metabolism of biological substances, the biosynthesis of secondary metabolites, and defense systems. They also provide a series of candidate miRNAs and transcription factors for taxol biosynthesis.BACKGROUND The tumor suppressor p53 is a major regulator of the DNA damage response and has been suggested to selectively bind and activate cell-type specific gene expression programs. However recent studies and meta-analyses of genomic data propose largely uniform, and condition independent p53 binding and thus question the selective and cell-type dependent function of p53. RESULTS To systematically assess the cell-type specificity of p53, we measured its association with DNA in 12 p53 wild-type cancer cell lines, from a range of epithelial linages, in response to ionizing radiation. We found that the majority of bound sites were occupied across all cell lines, however we also identified a subset of binding sites that were specific to one or a few cell lines. Unlike the shared p53-bound genome, which was not dependent on chromatin accessibility, the association of p53 with these atypical binding sites was well explained by chromatin accessibility and could be modulated by forcing cell state changes such as the epithelial-to-mesenchymal transition. CONCLUSIONS Our study reconciles previous conflicting views in the p53 field, by demonstrating that although the majority of p53 DNA binding is conserved across cell types, there is a small set of cell line specific binding sites that depend on cell state.BACKGROUND The virulence of the plant pathogen Xanthomonas campestris pv. campestris (Xcc) involves the coordinate expression of many virulence factors, including surface appendages flagellum and type IV pili, which are required for pathogenesis and the colonization of host tissues. Despite many insights gained on the structure and functions played by flagellum and pili in motility, biofilm formation, surface attachment and interactions with bacteriophages, we know little about how these appendages are regulated in Xcc. RESULTS Here we present evidence demonstrating the role of two single domain response regulators PilG and PilH in the antagonistic control of flagellum-dependent (swimming) and pili-dependent (swarming) motility. Using informative mutagenesis, we reveal PilG positively regulates swimming motility while and negatively regulating swarming motility. Conversely, PilH negatively regulates swimming behaviour while and positively regulating swarming motility. By transcriptome analyses (RNA-seq and RT-PCR) we confirm these observations as PilG is shown to upregulate many genes involved chemotaxis and flagellar biosynthesis but these similar genes were downregulated by PilH. Co-immunoprecipitation, bacterial two-hybrid and pull-down analyses showed that PilH and PilG were able to interact with district subsets of proteins that potentially account for their regulatory impact. Additionally, we present evidence, using mutagenesis that PilG and PilH are involved in other cellular processes, including chemotaxis and virulence. CONCLUSIONS Taken together, we demonstrate that for the conditions tested PilG and PilH have inverse regulatory effects on flagellum-dependent and pili-dependent motility in Xcc and that this regulatory impact depends on these proteins influences on genes/proteins involved in flagellar biosynthesis and pilus assembly.BACKGROUND The influenza virus spreads rapidly around the world in seasonal epidemics, resulting in significant morbidity and mortality. Influenza-related incidence data are limited in many countries in Africa despite established sentinel surveillance. This study aimed to address the information gap by estimating the burden and seasonality of medically attended influenza like illness in Ethiopia. METHOD Influenza sentinel surveillance data collected from 3 influenza like illness (ILI) and 5 Severe Acute Respiratory Illness (SARI) sites from 2012 to 2017 was used for analysis. Descriptive statistics were applied for simple analysis. The proportion of medically attended influenza positive cases and incidence rate of ILI was determined using total admitted patients and catchment area population. Seasonality was estimated based on weekly trend of ILI and predicted threshold was done by applying the "Moving Epidemic Method (MEM)". RESULT A total of 5715 medically attended influenza suspected patients who fulfills her study need to be considered to identify potential risks and improving the surveillance system to continue early detection and monitoring of circulating influenza virus in the country has paramount importance.BACKGROUND Understanding cellular and molecular heterogeneity in glioblastoma (GBM), the most common and aggressive primary brain malignancy, is a crucial step towards the development of effective therapies. Besides the inter-patient variability, the presence of multiple cell populations within tumors calls for the need to develop modeling strategies able to extract the molecular signatures driving tumor evolution and treatment failure. With the advances in single-cell RNA Sequencing (scRNA-Seq), tumors can now be dissected at the cell level, unveiling information from their life history to their clinical implications. RESULTS We propose a classification setting based on GBM scRNA-Seq data, through sparse logistic regression, where different cell populations (neoplastic and normal cells) are taken as classes. The goal is to identify gene features discriminating between the classes, but also those shared by different neoplastic clones. The latter will be approached via the network-based twiner regularizer to identify gene signatures shared by neoplastic cells from the tumor core and infiltrating neoplastic cells originated from the tumor periphery, as putative disease biomarkers to target multiple neoplastic clones. Our analysis is supported by the literature through the identification of several known molecular players in GBM. Moreover, the relevance of the selected genes was confirmed by their significance in the survival outcomes in bulk GBM RNA-Seq data, as well as their association with several Gene Ontology (GO) biological process terms. CONCLUSIONS We presented a methodology intended to identify genes discriminating between GBM clones, but also those playing a similar role in different GBM neoplastic clones (including migrating cells), therefore potential targets for therapy research. Our results contribute to a deeper understanding on the genetic features behind GBM, by disclosing novel therapeutic directions accounting for GBM heterogeneity.BACKGROUND Klebsiella pneumoniae is considered the most clinically relevant species of Enterobacteriaceae, known to cause severe infections including liver abscesses. To the best of our knowledge, a large proportion of iron in the human body is accumulated and stored in the liver. We hypothesize that increased iron availability is an important factor driving liver abscess formation and we therefore aim to understand the effects of iron on K. pneumoniae causing liver abscesses. RESULTS All tested K. pneumoniae clinical isolates, including those isolated from liver abscesses and other abdominal invasive infection sites, grew optimally when cultured in LB broth supplemented with 50 μM iron and exhibited the strongest biofilm formation ability under those conditions. Decreased growth and biofilm formation ability were observed in all tested strains when cultured with an iron chelator (P  less then  0.05). The infection model of G. mellonella larvae indicated the virulence of liver abscess-causing K. pneumoniae (2/3) cultured in LB broth with additional iron was significantly higher than those under iron-restricted conditions (P  less then  0.05). The relative expression levels of the four siderophore genes (iucB, iroB, irp1, entB) in K. pneumoniae strains isolated from liver abscesses cultured with additional iron were lower than those under iron-restricted conditions (P  less then  0.05). CONCLUSIONS It is suggested by our research that iron in the environment can promote growth, biofilm formation and enhance virulence of K. pneumoniae causing liver abscesses. A lower expression of siderophore genes correlates with increased virulence of liver abscess-causing K. pneumoniae. Further deeper evaluation of these phenomena is warranted.