The homologous recombination repair (HRR) pathway repairs DNA double-strand breaks in an error-free manner. Mutations in HRR genes can result in increased mutation rate and genomic rearrangements, and are associated with numerous genetic disorders and cancer. Despite intensive research, the HRR pathway is not yet fully mapped. Phylogenetic profiling analysis, which detects functional linkage between genes using coevolution, is a powerful approach to identify factors in many pathways. Nevertheless, phylogenetic profiling has limited predictive power when analyzing pathways with complex evolutionary dynamics such as the HRR. To map novel HRR genes systematically, we developed clade phylogenetic profiling (CladePP). CladePP detects local coevolution across hundreds of genomes and points to the evolutionary scale (e.g., mammals, vertebrates, animals, plants) at which coevolution occurred. We found that multiscale coevolution analysis is significantly more biologically relevant and sensitive to detect gene function. By using CladePP, we identified dozens of unrecognized genes that coevolved with the HRR pathway, either globally across all eukaryotes or locally in different clades. We validated eight genes in functional biological assays to have a role in DNA repair at both the cellular and organismal levels. These genes are expected to play a role in the HRR pathway and might lead to a better understanding of missing heredity in HRR-associated cancers (e.g., heredity breast and ovarian cancer). Our platform presents an innovative approach to predict gene function, identify novel factors related to different diseases and pathways, and characterize gene evolution.
Objectives: Blood culture contamination carries risks for patients, such as unnecessary antimicrobial therapy and other additional hazards and costs. One method shown to be effective in reducing contamination is initial blood specimen diversion during collection. We hypothesized that initial blood specimen diversion without a designated device or procedure would suffice for reduction in blood culture contamination rate. Methods: From 1 September 2017 through to 6 September 2018, we conducted a randomized controlled trial to assess the effect of an initial-specimen diversion technique (ISDT) on the rate of blood-culture contamination by changing the order of sampling using regular vacuum specimen tubes instead of commercially available sterile diversion devices. We included adults from whom the treating physician planned to take blood cultures and additional blood chemistry tests. Additionally, we evaluated the potential economic benefits of an ISDT. This was a researcher-initiated trial, Clinicaltrials.gov NCT03088865. Results: In all, 756 patients were enrolled. This method, compared with the standard procedure in use at our medical centre, reduced contamination by 66% (95% CI 17%e86%), from 20/400 (5%) with the standard method to 6/356 (1.6%) with the ISDT, without compromising detection of true bloodstream infection and at no additional cost. Hospital-wide implementation of ISDT was associated with a 1.1% saving in hospitalization days. Conclusions: We offer this novel approach as a simple, cost-effective measure to reduce risks to patient safety from contaminated blood cultures, without the need for using costly devices.
BackgroundContaminated blood cultures remain a challenge for patients, physicians, and microbiology laboratories, often leading to unnecessary antibiotic treatment. One approach to reduce contamination is to avoid culturing the initial blood sample that can contain a contaminated plug of skin from the needle stick. Initial specimen diversion technique (ISDT) was associated with decreased rate of blood culture contamination, when applied by trained phlebotomists, using either sterile vacuum blood collection tubes or a designated device. The aim of this study was to test ISDT in real-life, using externally nonsterile regular vacuum sample tubes for the diversion, by any medical personnel taking blood cultures.MethodsAdults from whom the treating physician planned to take blood cultures and additional blood chemistry tests, in the same venous puncture, were eligible and were randomly assigned to intervention or control arms. The hospital’s standard procedure for blood drawing was maintained, except that in the intervention arm, blood was aspirated to a green-capped tube, which was used for regular biochemistry tests, prior to the blood culture.ResultsFour hundred twenty-three blood cultures were obtained from 404 patients. Of 404 (11.1%) of the blood cultures, 45 yielded microbial growth, with 31 (7.7%) regarded as true pathogens and 14 (3.5%) as contaminants. Detection of true bloodstream infection was similar by the two methods, 16/181 (8.83%) with the ISDT, and 15/223 (6.72%) using the standard method. The ISDT was associated with a significantly less isolation of presumed contaminants compared with the standard method, 2/165 (1.2%) vs. 12/208 (5.76%), P = 0.02.ConclusionISDT, by any medical personnel, through altered order of test tube vs. blood culture sampling significantly reduced contamination of blood cultures without loss of diverted blood.Disclosures All authors: No reported disclosures.
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