scholarly journals Clinical and Genomic Characterization of Recurrent Enterococcal Bloodstream Infection in Patients With Acute Leukemia

2018 ◽  
Vol 5 (6) ◽  
Author(s):  
Julia A Messina ◽  
Rohita Sinha ◽  
Kimberly Starr ◽  
Mehreen Arshad ◽  
Barbara D Alexander ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Whole Genome Sequencing ◽  
Bloodstream Infection ◽  
Genome Sequencing ◽  
Genetic Relatedness ◽  
Categorical Variables ◽  
Genetic Lineage ◽  
Whole Genome ◽  
Sequencing Analysis ◽  
Continuous Variables

Abstract Background Rates and risk factors for recurrent enterococcal bloodstream infection (R-EBSI) and whether the same genetic lineage causes index EBSI and R-EBSI are unknown in patients with acute leukemia (AL) receiving chemotherapy. Methods Ninety-two AL patients with EBSI from 2010 to 2015 were included. Enterococcal bloodstream infection was defined by 31 positive blood cultures for Enterococcus faecium or Enterococcus faecalis and fever, hypotension, or chills. Clearance was defined by 31 negative cultures 324 hours after last positive culture and defervescence. Recurrent enterococcal bloodstream infection was defined by a positive blood culture for Enterococcus 324 hours after clearance. Categorical variables were reported as proportions and compared by the χ2 test. Continuous variables were summarized by median and interquartile range (IQR) and compared by the Wilcoxon-Mann-Whitney Test. P values <.05 were considered significant. Whole-genome sequencing was performed on available paired BSI isolates from 7 patients. Results Twenty-four patients (26%) had 31 episodes of R-EBSI. Median time to R-EBSI (IQR) was 26 (13–50) days. Patients with R-EBSI had significantly longer durations of fever and metronidazole exposure during their index EBSI. Thirty-nine percent of E. faecium R-EBSI isolates became daptomycin-nonsusceptible Enterococcus (DNSE) following daptomycin therapy for index EBSI. Whole-genome sequencing analysis confirmed high probability of genetic relatedness of index EBSI and R-EBSI isolates for 4/7 patients. Conclusions Recurrent enterococcal bloodstream infection and DNSE are common in patients with AL and tend to occur within the first 30 days of index EBSI. Duration of fever and metronidazole exposure may be useful in determining risk for R-EBSI. Whole-genome sequencing analysis demonstrates that the same strain causes both EBSI and R-EBSI in some patients.

scholarly journals Retrospective whole-genome sequencing analysis distinguished PFGE and drug resistance matched retail meat and clinical Salmonella isolates

2018 ◽  
Author(s):  
Andrea B. Keefer ◽  
Lingzi Xiaoli ◽  
Nkuchia M. M’ikanatha ◽  
Kuan Yao ◽  
Maria Hoffmann ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Genetic Relatedness ◽  
Whole Genome ◽  
Sequencing Analysis ◽  
Foodborne Illnesses ◽  
Multiple Sources ◽  
Genetic Characteristics ◽  
Retail Meats ◽  
Retail Meat

AbstractNon-typhoidal Salmonella are a leading cause of outbreak and sporadic-associated foodborne illnesses in the U.S. These infections have been associated with a range of foods, including retail meats. Traditionally, pulsed-field gel electrophoresis (PFGE) and antibiotic susceptibility testing (AST) have been used to facilitate public health investigations of Salmonella infections. However, whole-genome sequencing (WGS) has emerged as an alternative tool that can be routinely implemented. To assess its potential in enhancing integrated surveillance in Pennsylvania, WGS was used to directly compare the genetic characteristics of 7 retail meat and 43 clinical historic Salmonella isolates, subdivided into three subsets based on PFGE and AST results, to retrospectively resolve their genetic relatedness and identify antimicrobial resistance (AMR) determinants. Single nucleotide polymorphism (SNP) analyses revealed the retail meat isolates within S. Heidelberg, S. Typhimurium var. O5- subset 1, and S. Typhimurium var. O5- subset 2 were separated from each primary PFGE pattern-matched clinical isolate by 6-12, 41-96, and 21-81 SNPs, respectively. Fifteen resistance genes were identified across all isolates, including fosA7, a gene only recently found in a limited number of Salmonella and a ≥ 95% phenotype to genotype correlation was observed for all tested antimicrobials. Moreover, AMR was primarily plasmid-mediated in S. Heidelberg and S. Typhimurium var. O5- subset 2; whereas, AMR was chromosomally-carried in S. Typhimurium var. O5- subset 1. Similar plasmids were identified in both the retail meat and clinical isolates. Collectively, these data highlight the utility of WGS in retrospective analyses and enhancing integrated surveillance of Salmonella from multiple sources.

scholarly journals Sarek: A portable workflow for whole-genome sequencing analysis of germline and somatic variants

2018 ◽  
Author(s):  
Maxime Garcia ◽  
Szilveszter Juhos ◽  
Malin Larsson ◽  
Pall I. Olason ◽  
Marcel Martin ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Open Source ◽  
Genome Sequencing ◽  
Development Project ◽  
Whole Genome ◽  
Sequencing Analysis ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Insertion And Deletion ◽  
Sample Heterogeneity

AbstractSummaryWhole-genome sequencing (WGS) is a cornerstone of precision medicine, but portable and reproducible open-source workflows for WGS analyses of germline and somatic variants are lacking. We present Sarek, a modular, comprehensive, and easy-to-install workflow, combining a range of software for the identification and annotation of single-nucleotide variants (SNVs), insertion and deletion variants (indels), structural variants, tumor sample heterogeneity, and karyotyping from germline or paired tumor/normal samples. Sarek is implemented in a bioinformatics workflow language (Nextflow) with Docker and Singularity compatible containers, ensuring easy deployment and full reproducibility at any Linux based compute cluster or cloud computing environment. Sarek supports the human reference genomes GRCh37 and GRCh38, and can readily be used both as a core production workflow at sequencing facilities and as a powerful stand-alone tool for individual research groups.AvailabilitySource code and instructions for local installation are available at GitHub (https://github.com/SciLifeLab/Sarek) under the MIT open-source license, and we invite the research community to contribute additional functionality as a collaborative open-source development project.

scholarly journals Whole-genome sequencing analysis of Y chromosome microdeletion: a case report

2020 ◽  
Vol 48 (12) ◽  
pp. 030006052097649
Author(s):  
Zhixiang Gao ◽  
Feng Yuan ◽  
Qiaoqiao Li ◽  
Renlan Xia ◽  
Kai Fu ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Y Chromosome ◽  
Genome Sequencing ◽  
Sperm Quality ◽  
Sperm Count ◽  
Therapeutic Targets ◽  
Camp Signaling ◽  
Whole Genome ◽  
Sequencing Analysis ◽  
Y Chromosome Microdeletion

The mechanisms by which Y chromosome microdeletions cause infertility have been well described; however, the therapeutic targets remain a challenge. Here, we used whole-genome sequencing to explore the mechanism of Y chromosome deletion and potential therapeutic targets in a patient with infertility. There were no abnormalities in the patient’s medical history. Routine semen analysis showed immotile sperm and only two motile spermatozoa were occasionally see after centrifugation, indicating that the direct cause of infertility was an abnormal sperm count and motility. A Y chromosome microdeletion test revealed partial deletion of the AZFc region, including AZFc1, AZFc2, AZFc3, and AZFc4. Whole-genome sequencing showed that the patient had seven harmful mutations, with only one significant epigenetic mutation, SH3KBP1. Gene Ontology analysis of these meaningful mutations indicated involvement of cAMP signaling pathways. The patient’s wife became pregnant following in vitro fertilization, and no significant abnormalities were found during prenatal examination. This case suggests that Y chromosome microdeletion and gene mutation may affect the cAMP signaling pathway, leading to reduced sperm quality and male infertility.

484 Whole Genome Sequencing Analysis of Gastroparesis

2019 ◽  
Vol 114 (1) ◽  
pp. S280-S281
Author(s):  
Sandra P. Smieszek ◽  
Jesse L. Carlin ◽  
Gunther Birznieks ◽  
Mihael H. Polymeropoulos
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Whole Genome ◽  
Sequencing Analysis
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