Featured Publication
Ralstonia pickettii and Pseudomonas aeruginosa Bloodstream Infections Associated with Contaminated Extracorporeal Membrane Oxygenation Water Heater Devices
After tracking a rash of unusual infections, Brigham and Women’s Hospital’s infection control team called on epiXact, our rapid, whole-genome sequencing (WGS) service using single-nucleotide polymorphism analysis, to help trace outbreak strains of Burholderia, Ralstonia picketti and Pseudomonas aeruginosa. With the high resolution offered by WGS, the infection control team was able to conclusively link the outbreak with (ECMO) water heater devices which would have been otherwise challenging due to the prevalence of multiple species collected from various locations.
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Ralstonia pickettii and Pseudomonas aeruginosa Bloodstream Infections Associated with Contaminated Extracorporeal Membrane Oxygenation Water Heater Devices
After tracking a rash of unusual infections, Brigham and Women’s Hospital’s infection control team called on epiXact, our rapid, whole-genome sequencing (WGS) service using single-nucleotide polymorphism analysis, to help trace outbreak strains of Burholderia, Ralstonia picketti and Pseudomonas aeruginosa. With the high resolution offered by WGS, the infection control team was able to conclusively link the outbreak with (ECMO) water heater devices which would have been otherwise challenging due to the prevalence of multiple species collected from various locations.
View PublicationCluster of Burkholderia cepacia Complex Infections Associated with Extracorporeal Membrane Oxygenation Water Heater Devices
Our epiXact healthcare-associated infection (HAI) service helped Brigham and Women’s hospital link a cluster of Burkholderia cepacia complex infections in cardiothoracic ICU patients to contaminated Extracorporeal Membrane Oxygenation Water Heater Devices.
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Shiga Toxin–Producing Escherichia coli Transmission
via Fecal Microbiota Transplant
Our epiXact service for healthcare-associated infections (HAIs) confirmed the first known report of an undetected transmission of Shiga toxin-producing E. coli (STEC) in a fecal microbiota transplantation, despite enzyme-based STEC screening having been performed on donor samples. Following epiXact’s actionable findings, OpenBiome worked, in consultation with the FDA, to implement prospective PCR-based testing to enhance patient safety and avoid future transmissions.
View PublicationCommunity-acquired in name only: A cluster of carbapenem-resistant Acinetobacter baumannii in a burn intensive care unit and beyond
Mass General Hospital used our epiXact service to rapidly identify and respond to a highly-resistant A. baumannii outbreak in an ICU burn unit that was initially believed to be caused by community-transmission.
View PublicationPlasmids and genes contributing to high-level quinolone resistance in Escherichia coli
This research on an E. coli strain with a remarkably high resistance to broad-spectrum antibiotics helps us better understand the transmission of antibiotic resistance between strains via plasmids.
View PublicationDrug-Resistant E. coli Bacteremia Transmitted by Fecal Microbiota Transplant
Our epiXact service was used by Mass General Hospital to provide high-resolution whole genome sequencing analysis in less than two days to help uncover the cause of the first known fecal matter transplant patient death.
View PublicationMultiple Copies of qnrA1 on an IncA/C2 Plasmid Explain Enhanced Quinolone Resistance in an Escherichia coli Mutant
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Abstracts and Posters
Identification of subclinical healthcare-associated clusters of Staphylococcus epidermidis in an orthopedic patient population
Results presented by New England Baptist Hospital (NEBH) on the use of our epiXact PRO service to investigate genetic, epidemiologic, and environmental factors contributing to positive S. epidermidis joint cultures and prosthetic joint infection. S. epidermidis isolates from hip or knee cultures were identified and obtained between 2017-2020 from patients with one or more prior intraarticular procedures from NEBH. Whole-genome sequencing and single nucleotide polymorphism (SNP) based clonality analysis was performed using the epiXact service. This included species identification, in silico multi-locus sequence typing (MLST), phylogenomic analysis, along with genotypic assessment of the prevalence of specific antibiotic resistance and virulence genes.
Download PDFValidation of epiXact: Robust Bacterial Relatedness and Outbreak Detection Pipeline for WGS Data ECCMID 2022
Large-scale validation for Clinical Laboratory Improvement Amendments (CLIA ) certification for epiXact, our automated computational pipeline for detecting pathogen relatedness from WGS data. The epiXact pipeline demonstrated high accuracy for determining clonality between bacterial isolates across 5 species achieving 100% analytical sensitivity and 98.5% analytical specificity in determining clonality, and 100% repeatability.
Download PDFHigh concordance between short and long read sequencing for genomics-based species identification and antimicrobial resistance
This poster demonstrates the sustainability of ONT sequencing in the diagnosis and identification of bacterial infections and potential microbial resistance. We assessed the performance of Illumina short-read versus ONT long-read whole genome sequencing (WGS) data for species identification (ID) and antimicrobial susceptibility test (AST). The results were a high degree of concordance for ID (99.4%) and AST (97.7%) between the two sequencing platforms. Advances in nanopore sequencing have the potential to transform infectious disease diagnosis, cutting costs and leading to faster, more efficient treatments.
Download PDFSame-day transmission analysis of nosocomial transmission using nanopore whole-genome sequencing
This poster demonstrates the utility of the Oxford Nanopore Technologies (ONT) platform, a rapid sequencing technology, for use with our epiXact healthcare-associated infection (HAI) service. ONT sequencing offers many advantages with faster speed and lower costs over short-read technologies that could prove to be an attractive platform for the commercial epiXact service reducing turnaround time from ≥34-46 hours to same day service and pave the way for real-time HAI transmission detection and prospective outbreak warning system.
Download PDFUncluttering Case Clusters: Use of Rapid Sequencing to Exclude Transmission Events
Results presented by Mass General Hospital (MGH) on the use of epiXact healthcare-associated infection (HAI) service to investigate a cluster of methicillin-resistant Staphylococcus aureus (MRSA) and a cluster of carbapenem-resistant Enterobacterales (CRE) inpatient nosocomial infections. Whole-genome sequencing results allowed for early discontinuation of cluster investigations and conservation of resources.
Download PDFKeynome g-AST: Development of a Novel Machine Learning Method for Determining Bacterial Antibiotic Susceptibility from Genomic Sequences
This poster presents Keynome g-AST (genomic-AST), our data-driven approach to determining antibiotic susceptibility from genomic sequences. Keynome g-AST was trained and validated using our MicrohmDB dataset that consists of the whole genome sequences of over 45,000 microbial pathogens matched with their phenotypically derived AST results. Results show that Keynome g-AST is a promising method for determining the AST profile of pathogens and enable rapid culture-free AST diagnostics.
Download PDFepiXact : Rapid, precise and robust bacterial relatedness and outbreak detection from WGS data
This poster analyzes recent results of our epiXact service for healthcare-associated infections (HAIs). The poster highlights results from 24 recent cases of suspected HAIs submitted for epiXact investigation by clinical customers, encompassing a total of 116 bacterial samples across 12 different pathogens. The analysis demonstrated epiXact’s robust ability to detect outbreaks quickly, leveraging the automated and precise algorithm to provide conclusive evidence of 16 outbreak cases within 24-48 hours from sample receipt. With these rapid results, infection control specialists can make timely and accurate decisions to get the infection outbreak back under control.
Download PDFPilot study of a novel whole-genome sequencing based rapid bacterial identification assay in patients with bacteremia
This is the first proof-of-concept feasibility study in an inpatient clinical setting of our culture-free, species agnostic process using whole genome sequencing and algorithmic tools for identifying the species and antimicrobial resistance profile of a bloodstream infection in real-time. The results suggest the approach is potentially more sensitive and significantly faster than gold standard culture-based diagnostics.
Download PDFBlood2Bac: species ID and AMR prediction of bacterial pathogens at low concentrations in blood using a rapid ultra-high enrichment process and nanopore sequencing
This study demonstrated Blood2Bac’s ability, when paired with Keynome, to test for a broad range of infections (50 bacterial species) and recover almost the entirety of the pathogen’s genome directly from whole blood. The results represent a significant advancement over current molecular diagnostic approaches that are limited to testing just a handful of species and recover a very small portion of the pathogen’s genetic code.
Download PDFBacDetect: Development of a rapid, ultra-sensitive platform for bacterial detection from blood
To address slow turnaround times related to culture-based diagnostics for blood stream infections, we have developed BacDetect, a rapid DNA amplification-based detection method that determines the presence of gram-positive or gram-negative bacteria in a sample in 30 minutes.
Download PDFDemocratizing Sequencing for Infection Control: A Scalable, Automated Pipeline for WGS Analysis for Outbreak Detection
This abstract describes how our technology stack for detecting healthcare-associated infections (HAIs) can efficiently analyze large-scale datasets. Including a recent analysis of over 5,000 clinical bacterial samples collected between 2015 and 2019 which uncovered previously unidentified transmission clusters. With this robust technology stack, we can scale to analyze tens of thousands of samples and support infection control teams in performing prospective outbreak detection without the need for specialized computational biology training.
Download PDFRapid ultra-high enrichment of bacterial pathogens at low concentration from whole blood for species ID and AMR prediction using Oxford Nanopore sequencing
Blood2BacTM is our species-agnostic culture-free method for enriching bacterial DNA directly from whole blood samples by a factor of 100,000,000. When this is coupled with rapid whole genome sequencing and our algorithmic tools, we can determine bacterial species identification and antimicrobial resistance within hours instead of days with culture.
Download PDFMulti-copy qnrA1 Plasmid Causes Elevated Quinolone Resistance in E. coli
Analyzing the role large multi-drug resistance (MDR) plasmids play in cultivating resistance can be tremendously challenging. In this work, we leverage nanopore long-read sequencing to overcome these challenges and produced a complete sequence of an MDR plasmid with multiple copies of resistance genes that appeared to significantly increase resistance to ciprofloxacin in E. coli strains carrying the plasmid.
Download PDFAchievement of rapid whole genome coverage of bacterial pathogens at 1 CFU/mL in blood
Using whole genome sequencing for culture-free diagnosis of bacterial bloodstream infections is difficult because very little bacterial DNA is present in a clinical sample. Human DNA outnumbers bacterial DNA by 8-9 orders of magnitude. This work describes how we are able to rapidly enrich and sequence bacterial DNA for diagnosing bacterial bloodstream infections directly from clinical blood samples.
Download PDFcounterr: Characterization of Context Dependent MinION Sequencing Errors
In this work we described how we used counterr, our lightweight command line tool to characterize the error distributions in both amplified and native microbial ONT MinION sequencing data. Our results confirm a widely held belief that errors in MinION data strongly depend on sequence context. We hope that this improved error characterization can be useful for read error correction.
Download PDFQuantification of Predictive Power of Genomic Resistance Locus Databases Reveals Potential Limitations of Marker-Based Diagnostics
Tools that rapidly and accurately predict the antibiotic resistance of a clinical infection promise to allow healthcare providers to quickly provide targeted, effective treatments to patients. However, most emerging diagnostic approaches detect the presence or absence of only a limited panel of resistance markers. In the this work we analyze the power of genomic resistance locus databases to predict the resistance profiles of Staphylococcus aureus, Streptococcus pneumonia, and Mycobacterium tuberculosis clinical isolates.
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