GEM-TREND: a web tool for gene expression data mining toward relevant network discovery

<p>Abstract</p> <p>Background</p> <p>DNA microarray technology provides us with a first step toward the goal of uncovering gene functions on a genomic scale. In recent years, vast amounts of gene expression data have been collected, much of which are available in public databases, such as the Gene Expression Omnibus (GEO). To date, most researchers have been manually retrieving data from databases through web browsers using accession numbers (IDs) or keywords, but gene-expression patterns are not considered when retrieving such data. The Connectivity Map was recently introduced to compare gene expression data by introducing gene-expression signatures (represented by a set of genes with up- or down-regulated labels according to their biological states) and is available as a web tool for detecting similar gene-expression signatures from a limited data set (approximately 7,000 expression profiles representing 1,309 compounds). In order to support researchers to utilize the public gene expression data more effectively, we developed a web tool for finding similar gene expression data and generating its co-expression networks from a publicly available database.</p> <p>Results</p> <p>GEM-TREND, a web tool for searching gene expression data, allows users to search data from GEO using gene-expression signatures or gene expression ratio data as a query and retrieve gene expression data by comparing gene-expression pattern between the query and GEO gene expression data. The comparison methods are based on the nonparametric, rank-based pattern matching approach of Lamb et al. (Science 2006) with the additional calculation of statistical significance. The web tool was tested using gene expression ratio data randomly extracted from the GEO and with in-house microarray data, respectively. The results validated the ability of GEM-TREND to retrieve gene expression entries biologically related to a query from GEO. For further analysis, a network visualization interface is also provided, whereby genes and gene annotations are dynamically linked to external data repositories.</p> <p>Conclusion</p> <p>GEM-TREND was developed to retrieve gene expression data by comparing query gene-expression pattern with those of GEO gene expression data. It could be a very useful resource for finding similar gene expression profiles and constructing its gene co-expression networks from a publicly available database. GEM-TREND was designed to be user-friendly and is expected to support knowledge discovery. GEM-TREND is freely available at <url>http://cgs.pharm.kyoto-u.ac.jp/services/network</url>.</p

MicroRNA-338-3p and microRNA-451 contribute to the formation of basolateral polarity in epithelial cells

MicroRNAs are small noncoding RNA species, some of which are playing important roles in cell differentiation. However, the level of participations of microRNAs in epithelial cell differentiation is largely unknown. Here, utilizing an epithelial differentiation model with T84 cells, we demonstrate that miR-338-3p and miR-451 contribute to the formation of epithelial basolateral polarity by facilitating translocalization of β1 integrin to the basolateral membrane. Among 250 microRNAs screened in this study, the expression levels of four microRNAs (miR-33a, 210, 338-3p and 451) were significantly elevated in the differentiated stage of T84 cells, when epithelial cell polarity was established. To investigate the involvement of these microRNAs in terms of epithelial cell polarity, we executed loss-of- and gain-of-function analyses of these microRNAs. The blockade of endogenous miR-338-3p or miR-451 via each microRNA-specific antisense oligonucleotides inhibited the translocalization of β1 integrin to the basolateral membrane, whereas inhibition of miR-210 or miR-33a had no effect on it. On the other hand, simultaneous transfection of synthetic miR-338-3p and miR-451 accelerated the translocalization of β1 integrin to the basolateral membrane, although the introduction of individual synthetic microRNAs exhibited no effect. Therefore, we concluded that both miR-338-3p and miR-451 are necessary for the development of epithelial cell polarity

Application of a New Scaffold Concept for Computational Target Deconvolution of Chemical Cancer Cell Line Screens

Target deconvolution of phenotypic assays is a hot topic in chemical biology and drug discovery. The ultimate goal is the identification of targets for compounds that produce interesting phenotypic readouts. A variety of experimental and computational strategies have been devised to aid this process. A widely applied computational approach infers putative targets of new active molecules on the basis of their chemical similarity to compounds with activity against known targets. Herein, we introduce a molecular scaffold-based variant for similarity-based target deconvolution from chemical cancer cell line screens that were used as a model system for phenotypic assays. A new scaffold type was used for substructure-based similarity assessment, termed analog series-based (ASB) scaffold. Compared with conventional scaffolds and compound-based similarity calculations, target assignment centered on ASB scaffolds resulting from screening hits and bioactive reference compounds restricted the number of target hypotheses in a meaningful way and lead to a significant enrichment of known cancer targets among candidates

286 new target pairs based on shared compounds from ChEMBL

<p>Reported is the list of 286 compound-based target pairs between distantly related or unrelated pharmaceutical target proteins with shared common compounds, derived from ChEMBL22 high-confidence data. For each target, the corresponding UniProt ID is provided. In addition, for each given target pair, the number of shared compounds and structures by SMILES notations are added as well.</p

The impact of a preoperative nurse-led orientation program on postoperative delirium after cardiovascular surgery: a retrospective single-center observational study

Abstract Background Postoperative delirium in intensive care is common and associated with mortality, cognitive impairment, prolonged hospital stays and high costs. We evaluate whether a nurse-led orientation program could reduce the incidence of delirium in the intensive care unit after cardiovascular surgery. Methods In this retrospective cohort study, we enrolled patients admitted to the intensive care unit for planned cardiovascular surgery between January 2020 and December 2021. A nurse-led orientation program based on a preoperative visit was routinely introduced from January 2021. We assessed the association between these visits and postoperative delirium in the intensive care unit. We also assessed predictors of postoperative delirium with baseline and intraoperative characteristics. Results Among 253 patients with planned cardiovascular surgery, 128 (50.6%) received preoperative visits. Valve surgery comprised 44.7%, coronary surgery 31.6%, and aortic surgery 20.9%. Cardiopulmonary bypass use and transcatheter surgery were 60.5% and 12.3%, respectively. Incidence of delirium was lower in patients that received preoperative visits, and median hospital stay was shorter than in those without visits (18 patients [14.1%] vs 34 patients [27.2%], P < 0.01; 14 days vs 17 days, P < 0.01). After adjusting predefined confounders, preoperative visits were independently associated with decreased incidence of delirium (adjusted odds ratio [aOR] 0.45; 95% confidence interval [95% CI] 0.22–0.84). Other predictors of delirium were higher European System for Cardiac Operative Risk Evaluation II score and lower minimum intraoperative cerebral oxygen saturation. Conclusions A preoperative nurse-led orientation program was associated with reduction of postoperative delirium and could be effective against postoperative delirium after cardiovascular surgery. Trial registration UMIN Clinical Trial Registry no. UMIN000048142. Registered 22, July, 2022, retrospectively registered, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000054862

Factors Attenuating Zinc Deficiency Improvement in Direct-Acting Antiviral Agent-Treated Chronic Hepatitis C Virus Infection

Zinc deficiency is frequently observed in chronic liver diseases. However, no studies have focused on the zinc status in chronic hepatitis C (HCV)-infected patients receiving direct-acting antiviral agents (DAAs). In this retrospective study, we assessed the serum zinc status in DAA-treated HCV patients with sustained virologic response for over two years (Zn-2y). Ninety-five patients were enrolled, whose baseline characteristics and blood parameters at DAA therapy initiation were collected. Baseline Zn &lt; 65 &#181;g/dL (odds ratio (OR) = 10.56, p &lt; 0.001) and baseline uric acid (UA) &gt; 5.5 mg/dL (OR = 9.99, p = 0.001) were independent risk factors for Zn-2y deficiency. A decision-tree algorithm classified low-baseline Zn and high-baseline UA as the first two variables, suggesting that baseline hypozincemia and hyperuricemia are prognosticators for long-term zinc deficiency. Baseline Zn was negatively correlated with the Fibrosis-4 (FIB-4) index, while baseline UA was significantly higher in habitual alcohol drinkers. In conclusion, serum zinc levels should be closely monitored, considering that zinc status improvement is related to liver fibrosis regression. Hyperuricemia indicates risks of developing metabolic disorders and subsequent zinc deficiency, for which an adjustment of personal lifestyle or dietary habits should be recommended clinically