scholarly journals Whole Genome Sequencing as a Diagnostic Test: Challenges and Opportunities

2014 ◽  
Vol 60 (5) ◽  
pp. 724-733 ◽  
Author(s):  
Caitlin C Chrystoja ◽  
Eleftherios P Diamandis
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Clinical Test ◽  
Whole Genome ◽  
Clinical Implementation ◽  
Technological Advances ◽  
Challenges And Opportunities ◽  
Patient Health ◽  
Therapeutic Decision Making ◽  
The Cost

Abstract BACKGROUND Extraordinary technological advances and decreases in the cost of DNA sequencing have made the possibility of whole genome sequencing (WGS) as a highly accessible clinical test for numerous indications feasible. There have been many recent, successful applications of WGS in establishing the etiology of complex diseases and guiding therapeutic decision-making in neoplastic and nonneoplastic diseases and in various aspects of reproductive health. However, there are major, but not insurmountable, obstacles to the increased clinical implementation of WGS, such as hidden costs, issues surrounding sequencing and analysis, quality assurance and standardization protocols, ethical dilemmas, and difficulties with interpretation of the results. CONTENT The widespread use of WGS in routine clinical practice remains a distant proposition. Prospective trials will be needed to establish if, and for whom, the benefits of WGS will outweigh the likely substantial costs associated with follow-up tests, the risks of overdiagnosis and overtreatment, and the associated emotional distress. SUMMARY WGS should be carefully implemented in the clinic to allow the realization of its potential to improve patient health in specific indications. To minimize harm the use of WGS for all other reasons must be carefully evaluated before clinical implementation.

scholarly journals Whole-Genome Sequencing for Bacterial Strain Typing Using the iSeq100 Platform

2020 ◽  
Vol 41 (S1) ◽  
pp. s434-s434
Author(s):  
Grant Vestal ◽  
Steven Bruzek ◽  
Amanda Lasher ◽  
Amorce Lima ◽  
Suzane Silbert
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Outbreak Detection ◽  
Epidemiological Surveillance ◽  
Whole Genome ◽  
Nucleotide Polymorphisms ◽  
Dna Libraries ◽  
Patient Health ◽  
Hospital Acquired ◽  
Reference Genomes

Background: Hospital-acquired infections pose a significant threat to patient health. Laboratories are starting to consider whole-genome sequencing (WGS) as a molecular method for outbreak detection and epidemiological surveillance. The objective of this study was to assess the use of the iSeq100 platform (Illumina, San Diego, CA) for accurate sequencing and WGS-based outbreak detection using the bioMérieux EPISEQ CS, a novel cloud-based software for sequence assembly and data analysis. Methods: In total, 25 isolates, including 19 MRSA isolates and 6 ATCC strains were evaluated in this study: A. baumannii ATCC 19606, B. cepacia ATCC 25416, E. faecalis ATCC 29212, E. coli ATCC 25922, P. aeruginosa ATCC 27853 and S. aureus ATCC 25923. DNA extraction of all isolates was performed on the QIAcube (Qiagen, Hilden, Germany) using the DNEasy Ultra Clean Microbial kit extraction protocol. DNA libraries were prepared for WGS using the Nextera DNA Flex Library Prep Kit (Illumina) and sequenced at 2×150-bp on the iSeq100 according to the manufacturer’s instructions. The 19 MRSA isolates were previously characterized by the DiversiLab system (bioMérieux, France). Upon validation of the iSeq100 platform, a new outbreak analysis was performed using WGS analysis using EPISEQ CS. ATCC sequences were compared to assembled reference genomes from the NCBI GenBank to assess the accuracy of the iSeq100 platform. The FASTQ files were aligned via BowTie2 version 2.2.6 software, using default parameters, and FreeBayes version 1.1.0.46-0 was used to call homozygous single-nucleotide polymorphisms (SNPs) with a minimum coverage of 5 and an allele frequency of 0.87 using default parameters. ATCC sequences were analyzed using ResFinder version 3.2 and were compared in silico to the reference genome. Results: EPISEQ CS classified 8 MRSA isolates as unrelated and grouped 11 isolates into 2 separate clusters: cluster A (5 isolates) and cluster B (6 isolates) with similarity scores of ≥99.63% and ≥99.50%, respectively. This finding contrasted with the previous characterization by DiversiLab, which identified 3 clusters of 2, 8, and 11 isolates, respectively. The EPISEQ CS resistome data detected the mecA gene in 18 of 19 MRSA isolates. Comparative analysis of the ATCCsequences to the reference genomes showed 99.9986% concordance of SNPs and 100.00% concordance between the resistance genes present. Conclusions: The iSeq100 platform accurately sequenced the bacterial isolates and could be an affordable alternative in conjunction with EPISEQ CS for epidemiological surveillance analysis and infection prevention.Funding: NoneDisclosures: None

scholarly journals Challenges and opportunities for strain verification by whole-genome sequencing

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jenna E. Gallegos ◽  
Sergei Hayrynen ◽  
Neil R. Adames ◽  
Jean Peccoud
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Whole Genome ◽  
Challenges And Opportunities

scholarly journals Reflections on the Cost of "Low-Cost" Whole Genome Sequencing: Framing the Health Policy Debate

PLoS Biology ◽  
2013 ◽  
Vol 11 (11) ◽  
pp. e1001699 ◽  
Author(s):  
Timothy Caulfield ◽  
Jim Evans ◽  
Amy McGuire ◽  
Christopher McCabe ◽  
Tania Bubela ◽  
...  
Keyword(s):  
Health Policy ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Low Cost ◽  
Whole Genome ◽  
Policy Debate ◽  
The Cost

scholarly journals Method for Economic Evaluation of Bacterial Whole Genome Sequencing Surveillance Compared to Standard of Care in Detecting Hospital Outbreaks

2020 ◽  
Author(s):  
Praveen Kumar ◽  
Alexander J Sundermann ◽  
Elise M Martin ◽  
Graham M Snyder ◽  
Jane W Marsh ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Economic Value ◽  
Positive Culture ◽  
Cost Effective ◽  
Standard Of Care ◽  
Whole Genome ◽  
Electronic Health Record Data ◽  
The Cost ◽  
And Control

Abstract Background Whole genome sequencing (WGS) surveillance and electronic health record data mining have the potential to greatly enhance the identification and control of hospital outbreaks. The objective was to develop methods for examining economic value of a WGS surveillance-based infection prevention (IP) program compared to standard of care (SoC). Methods The economic value of a WGS surveillance-based IP program was assessed from a hospital’s perspective using historical outbreaks from 2011–2016. We used transmission network of outbreaks to estimate incremental cost per transmission averted. The number of transmissions averted depended on the effectiveness of intervening against transmission routes, time from transmission to positive culture results and time taken to obtain WGS results and intervene on the transmission route identified. The total cost of an IP program included cost of staffing, WGS, and treating infections. Results Approximately 41 out of 89 (46%) transmissions could have been averted under the WGS surveillance-based IP program, and it was found to be a less costly and more effective strategy than SoC. The results were most sensitive to the cost of performing WGS and the number of isolates sequenced per year under WGS surveillance. The probability of the WGS surveillance-based IP program being cost-effective was 80% if willingness to pay exceeded $2400 per transmission averted. Conclusions The proposed economic analysis is a useful tool to examine economic value of a WGS surveillance-based IP program. These methods will be applied to a prospective evaluation of WGS surveillance compared to SoC.

scholarly journals Phenotype prediction and characterization of 25 pharmacogenes in Thais from whole genome sequencing for clinical implementation

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
John Mauleekoonphairoj ◽  
Monpat Chamnanphon ◽  
Apichai Khongphatthanayothin ◽  
Boosamas Sutjaporn ◽  
Pharawee Wandee ◽  
...  
Keyword(s):  
High Risk ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Structural Variation ◽  
Whole Genome ◽  
Clinical Implementation ◽  
Thai Population ◽  
Phenotype Prediction ◽  
Specific Variation

Abstract Publicly available pharmacogenomics (PGx) databases enable translation of genotype data into clinically actionable information. As variation within pharmacogenes is population-specific, this study investigated the spectrum of 25 clinically relevant pharmacogenes in the Thai population (n = 291) from whole genome sequencing. The bioinformatics tool Stargazer was used for phenotype prediction, through assignment of alleles and detection of structural variation. Known and unreported potentially deleterious PGx variants were identified. Over 25% of Thais carried a high-risk diplotype in CYP3A5, CYP2C19, CYP2D6, NAT2, SLCO1B1, and UGT1A1. CYP2D6 structural variants accounted for 83.8% of all high-risk diplotypes. Of 39 known PGx variants identified, six variants associated with adverse drug reactions were common. Allele frequencies of CYP3A5*3 (rs776746), CYP2B6*6 (rs2279343), and NAT2 (rs1041983) were significantly higher in Thais than East-Asian and global populations. 121 unreported variants had potential to exert clinical impact, majority were rare and population-specific, with 60.3% of variants absent from gnomAD database. This study demonstrates the population-specific variation in clinically relevant pharmacogenes, the importance of CYP2D6 structural variation detection in the Thai population, and potential of unreported variants in explaining drug response. These findings are essential in development of dosing guidelines, PGx testing, clinical trials, and drugs.

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