A user's guide to the Encyclopedia of DNA elements (ENCODE)

The mission of the Encyclopedia of DNA Elements (ENCODE) Project is to enable the scientific and medical communities to interpret the human genome sequence and apply it to understand human biology and improve health. The ENCODE Consortium is integrating multiple technologies and approaches in a collective effort to discover and define the functional elements encoded in the human genome, including genes, transcripts, and transcriptional regulatory regions, together with their attendant chromatin states and DNA methylation patterns. In the process, standards to ensure high-quality data have been implemented, and novel algorithms have been developed to facilitate analysis. Data and derived results are made available through a freely accessible database. Here we provide an overview of the project and the resources it is generating and illustrate the application of ENCODE data to interpret the human genome

Performance Evaluation of the Verigene Gram-Positive and Gram-Negative Blood Culture Test for Direct Identification of Bacteria and Their Resistance Determinants from Positive Blood Cultures in Hong Kong.

A multicenter study was conducted to evaluate the diagnostic performance and the time to identifcation of the Verigene Blood Culture Test, the BC-GP and BC-GN assays, to identify both Gram-positive and Gram-negative bacteria and their drug resistance determinants directly from positive blood cultures collected in Hong Kong.A total of 364 blood cultures were prospectively collected from four public hospitals, in which 114 and 250 cultures yielded Gram-positive and Gram-negative bacteria, and were tested with the BC-GP and BC-GN assay respectively. The overall identification agreement for Gram-positive and Gram-negative bacteria were 89.6% and 90.5% in monomicrobial cultures and 62.5% and 53.6% in polymicrobial cultures, respectively. The sensitivities for most genus/species achieved at least 80% except Enterococcus spp. (60%), K.oxytoca (0%), K.pneumoniae (69.2%), whereas the specificities for all targets ranged from 98.9% to 100%. Of note, 50% (7/14) cultures containing K.pneumoniae that were missed by the BC-GN assay were subsequently identified as K.variicola. Approximately 5.5% (20/364) cultures contained non-target organisms, of which Aeromonas spp. accounted for 25% and are of particular concern. For drug resistance determination, the Verigene test showed 100% sensitivity for identification of MRSA, VRE and carbapenem resistant Acinetobacter, and 84.4% for ESBL-producing Enterobacteriaceae based on the positive detection of mecA, vanA, blaOXA and blaCTXM respectively.Overall, the Verigene test provided acceptable accuracy for identification of bacteria and resistance markers with a range of turnaround time 40.5 to 99.2 h faster than conventional methods in our region

Difference in time to result between conventional culture-based method and the Verigene Test.

<p>^a Difference in time between BC-GP or BC-GN result and final culture-based identification and drug susceptibility test results</p><p>^b Only the isolates with concordant results from cultured-based method and the Verigene test were included for the time to result assessment.</p><p>Difference in time to result between conventional culture-based method and the Verigene Test.</p

Performance of BC-GP for identification of Gram positive organisms.

<p>^<i>a</i><i>95% confidence interval was calculated using Adjusted Wald Method (</i><a href="http://www.measuringu.com/wald.htm" target="_blank"><i>http</i>:<i>//www</i>.<i>measuringu</i>.<i>com/wald</i>.<i>htm</i></a>)</p><p>^b Misidentifed as <i>S</i>. <i>pneumoniae</i></p><p>Performance of BC-GP for identification of Gram positive organisms.</p

The identities of bacteria in cultures with discordant results reported by culture-based method and the Verigene Test.

<p>^a Organisms are not included in the Verigene Test identification panel</p><p>The identities of bacteria in cultures with discordant results reported by culture-based method and the Verigene Test.</p

Performance of BC-GN for idenifcation of Gram negative organisms.

<p>^a95% confidence interval was calculated using Adjusted Wald Method (<a href="http://www.measuringu.com/wald.htm" target="_blank">http://www.measuringu.com/wald.htm</a>)</p><p>^b Species were confirmed by 16s rRNA sequencing</p><p>^c Misidentified as <i>Enterobacter spp</i>. by BC-GN</p><p>^d Seven isolates were confirmed to be <i>K</i>. <i>variicola</i> instead of <i>K</i>. <i>pneumoniae</i>by 16s rRNA and yGGEsequencing. After the discrepancy resolution, the sensitivity for <i>K</i>. <i>pneumoniae</i> was raised to 80% (36/45).</p><p>^e One was misidentified as mixed culture of <i>K</i>. <i>pneumoniae</i> and <i>K</i>. <i>oxytoca</i> whereas the other one was misidentified as mixed cultured of <i>K</i>. <i>pneumoniae</i> and <i>Enterobacter</i></p><p>^f Misidentified as <i>K</i>. <i>oxytoca</i></p><p>Performance of BC-GN for idenifcation of Gram negative organisms.</p

Performance of Verigene Test in detection of drug resistant organisms.

<p>MRSA: Methicillin resistant <i>Staphylococcus aureus</i>; MRSE: Methicillin resistant <i>Staphylococcus epidermidis;</i> VRE: Vancomycin resistant Enterococcus; ESBL: Extended spectrum beta-lactamase; MDR <i>Acinetobacter</i>: Multidrug resisant <i>Acinetobacter</i></p><p>^a 95% confidence interval was calculated using Adjusted Wald Method (<a href="http://www.measuringu.com/wald.htm" target="_blank">http://www.measuringu.com/wald.htm</a>)</p><p>Performance of Verigene Test in detection of drug resistant organisms.</p

Resistance gene profile in Gram negative organisms collected in this study.

<p>^a species identified by 16s Sequencing</p><p>Resistance gene profile in Gram negative organisms collected in this study.</p

The overall concordance in bacterial identification between Verigene test and culture-based method in different study sites.

<p>QMH: Queen Mary Hospital; PMH: Princess Margaret Hospital; UCH: United Christian Hospital; PYNEH: Pamela Youde Nethersole Eastern Hospital; 95%CI: 95% confidence interval</p><p>^a 95% confidence interval was calculated using Adjusted Wald Method (<a href="http://www.measuringu.com/wald.htm" target="_blank">http://www.measuringu.com/wald.htm</a>)</p><p>The overall concordance in bacterial identification between Verigene test and culture-based method in different study sites.</p