DiscoverySpace: an interactive data analysis application

DiscoverySpace is a graphical application for bioinformatics data analysis. Users can seamlessly traverse references between biological databases and draw together annotations in an intuitive tabular interface. Datasets can be compared using a suite of novel tools to aid in the identification of significant patterns. DiscoverySpace is of broad utility and its particular strength is in the analysis of serial analysis of gene expression (SAGE) data. The application is freely available online

In Vivo, In Vitro, and In Silico Characterization of Peptoids as Antimicrobial Agents

Bacterial resistance to conventional antibiotics is a global threat that has spurred the development of antimicrobial peptides (AMPs) and their mimetics as novel anti-infective agents. While the bioavailability of AMPs is often reduced due to protease activity, the non-natural structure of AMP mimetics renders them robust to proteolytic degradation, thus offering a distinct advantage for their clinical application. We explore the therapeutic potential of N-substituted glycines, or peptoids, as AMP mimics using a multi-faceted approach that includes in silico, in vitro, and in vivo techniques. We report a new QSAR model that we developed based on 27 diverse peptoid sequences, which accurately correlates antimicrobial peptoid structure with antimicrobial activity. We have identified a number of peptoids that have potent, broad-spectrum in vitro activity against multi-drug resistant bacterial strains. Lastly, using a murine model of invasive S. aureus infection, we demonstrate that one of the best candidate peptoids at 4 mg/kg significantly reduces with a two-log order the bacterial counts compared with saline-treated controls. Taken together, our results demonstrate the promising therapeutic potential of peptoids as antimicrobial agents

Internet Contig Explorer (iCE)—A Tool for Visualizing Clone Fingerprint Maps

Fingerprinted clone physical maps have proven useful in various applications, supporting both whole-genome and region-specific DNA sequencing as well as gene cloning studies. Fingerprint maps have been generated for several genomes, including those of human, mouse, rat, the nematodes Caenorhabditis elegans and Caenorhabditis briggsae, Arabidopsis thaliana and rice. Fingerprint maps of other genomes, including those of fungi, bacteria, poplar, and the cow, are being generated. The increasing use of fingerprint maps in genomic research has spawned a need in the research community for intuitive computer tools that facilitate viewing of the maps and the underlying fingerprint data. In this report we describe a new Java-based application called iCE (Internet Contig Explorer) that has been designed to provide views of fingerprint maps and associated data. Users can search for and display individual clones, contigs, clone fingerprints, clone insert sizes and markers. Users can also load into the software lists of particular clones of interest and view their fingerprints. iCE is being used at our Genome Centre to offer up to the research community views of the mouse, rat, bovine, C. briggsae, and several fungal genome bacterial artificial chromosome (BAC) fingerprint maps we have either completed or are currently constructing. We are also using iCE as part of the Rat Genome Sequencing Project to manage our provision of rat BAC clones for sequencing at the Human Genome Sequencing Center at the Baylor College of Medicine

Cytokines and signaling molecules predict clinical outcomes in sepsis.

Inflammatory response during sepsis is incompletely understood due to small sample sizes and variable timing of measurements following the onset of symptoms. The vasopressin in septic shock trial (VASST) compared the addition of vasopressin to norepinephrine alone in patients with septic shock. During this study plasma was collected and 39 cytokines measured in a 363 patients at both baseline (before treatment) and 24 hours. Clinical features relating to both underlying health and the acute organ dysfunction induced by the severe infection were collected during the first 28 days of admission.Cluster analysis of cytokines identifies subgroups of patients at differing risk of death and organ failure.Circulating cytokines and other signaling molecules were measured using a Luminex multi-bead analyte detection system. Hierarchical clustering was performed on plasma values to create patient subgroups. Enrichment analysis identified clinical outcomes significantly different according to these chemically defined patient subgroups. Logistic regression was performed to assess the importance of cytokines for predicting patient subgroups.Plasma levels at baseline produced three subgroups of patients, while 24 hour levels produced two subgroups. Using baseline cytokine data, one subgroup of 47 patients showed a high level of enrichment for severe septic shock, coagulopathy, renal failure, and risk of death. Using data at 24 hours, a larger subgroup of 81 patients that largely encompassed the 47 baseline subgroup patients had a similar enrichment profile. Measurement of two cytokines, IL2 and CSF2 and their product were sufficient to classify patients into these subgroups that defined clinical risks.A distinct pattern of cytokine levels measured early in the course of sepsis predicts disease outcome. Subpopulations of patients have differing clinical outcomes that can be predicted accurately from small numbers of cytokines. Design of clinical trials and interventions may benefit from consideration of cytokine levels

Prolonged QTc affects short-term and long-term outcomes in patients with normal left ventricular function undergoing cardiac surgery

ObjectiveAlthough it is known that preoperative decreased left ventricular ejection fraction (LVEF) is a risk for morbidity and mortality after cardiac surgery, there are no reliable markers of risk in patients with preserved LVEF. This study examines whether a prolonged QTc interval is associated with adverse outcomes in patients with preoperative LVEF greater than 40% undergoing cardiac surgery.MethodsA retrospective chart review of patients who had cardiac surgery at St. Paul's Hospital in Vancouver, Canada, between 2004 and 2009, who had a preoperative LVEF greater than 40%, was undertaken. We tested for association of preoperative prolonged QTc interval with mortality and morbidity using unadjusted and adjusted analyses.ResultsFive-hundred and fifty-five patients with a preoperative LVEF greater than 40% were included in the study; 496 (89.4%) had cardiopulmonary bypass and the remainder were off pump. Preoperative prolonged QTc was associated with increased mortality at 30 days (P < .01), 90 days (P < .01), and 8 years (P < .01), and these results remained significant after adjusting for the clinical variables significantly associated with mortality (8-year odds ratio, 2.42; 95% confidence interval, 1.34-4.34; P = .003). Similar results were found when the analysis was restricted to the more homogeneous group of patients undergoing on-pump coronary artery bypass (CABG, n = 408). Prolonged QTc was also associated with prolonged intensive care unit stay (P = .02), prolonged hospital stay (P < .01), development of atrial arrhythmias (P = .02), and low cardiac output syndrome (on-pump CABG, P = .02).ConclusionsIn patients undergoing cardiac surgery and a preoperative LVEF greater than 40%, a prolonged QTc interval is associated with increased short-term and long-term mortality and increased perioperative morbidity, and therefore should be considered when assessing risk preoperatively

Levels of signaling molecules at 24 hours.

<p>Patient subgrouping, survival and features are indicated on the top colored rows. The <i>24 hr groups</i> are the Low and High subgroups based on 24 hour cytokines. The <i>Baseline groups</i> are the corresponding subgroups the patients are in using baseline data.</p

Cytokine levels at 24

<p>Concentrations of cytokines are shown for those having highest ratio between patient subgroups. Values are median, and interquartile ranges in pM. Ratio is the ratio of medians of High and Low cytokine subgroup values. The p-value is from t-test on log10-transformed cytokine values adjusted for multiple testing. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0079207#pone.0079207.s002" target="_blank">Table S2</a> for full list.</p