Deciphering Microbiota of Acute Upper Respiratory Infections: A Comparative Analysis of PCR and mNGS Methods for Lower Respiratory Trafficking Potential

Almas, Sadia; Carpenter, Rob E.; Singh, Anuradha; Rowan, Chase; Tamrakar, Vaibhav K; Sharma, Rahul

doi:10.3390/arm91010006

Cited by 5 publications

(4 citation statements)

References 83 publications

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“…However, even in its current qualitative format, this study demonstrates that PM has potential to influence diagnostic specificity and improve public health decisions. As technology continues to advance our understanding of the etiological relationship between microorganisms and their hosts, PM has the potential to bridge the gap between microbial research and diagnostic microbiology for UTIs and other infectious diseases ( Almas et al., 2023 ). Further studies are warranted to demonstrate the financial incentives for accurate and timely diagnosis leading to prompter patient recovery and savings in treatment costs.…”

Section: Discussionmentioning

confidence: 99%

Advantage of precision metagenomics for urinary tract infection diagnostics

Almas¹,

Carpenter

Rowan³

et al. 2023

Front. Cell. Infect. Microbiol.

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BackgroundUrinary tract infections (UTIs) remain a diagnostic challenge and often promote antibiotic overuse. Despite urine culture being the gold standard for UTI diagnosis, some uropathogens may lead to false-negative or inconclusive results. Although PCR testing is fast and highly sensitive, its diagnostic yield is limited to targeted microorganisms. Metagenomic next-generation sequencing (mNGS) is a hypothesis-free approach with potential of deciphering the urobiome. However, clinically relevant information is often buried in the enormous amount of sequencing data.MethodsPrecision metagenomics (PM) is a hybridization capture-based method with potential of enhanced discovery power and better diagnostic yield without diluting clinically relevant information. We collected 47 urine samples of clinically suspected UTI and in parallel tested each sample by microbial culture, PCR, and PM; then, we comparatively analyzed the results. Next, we phenotypically classified the cumulative microbial population using the Explify® data analysis platform for potential pathogenicity.ResultsResults revealed 100% positive predictive agreement (PPA) with culture results, which identified only 13 different microorganisms, compared to 19 and 62 organisms identified by PCR and PM, respectively. All identified organisms were classified into phenotypic groups (0–3) with increasing pathogenic potential and clinical relevance. This PM can simultaneously quantify and phenotypically classify the organisms readily through bioinformatic platforms like Explify®, essentially providing dissected and quantitative results for timely and accurate empiric UTI treatment.ConclusionPM offers potential for building effective diagnostic models beyond usual care testing in complex UTI diseases. Future studies should assess the impact of PM-guided UTI management on clinical outcomes.

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Section: Discussionmentioning

confidence: 99%

Advantage of precision metagenomics for urinary tract infection diagnostics

Almas¹,

Carpenter

Rowan³

et al. 2023

Front. Cell. Infect. Microbiol.

Self Cite

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“…This is attributed to the colonization of bacteria, viruses, fungi, and other microorganisms in the respiratory system, which mNGS can capture as free nucleic acids. Therefore, when interpreting mNGS results from respiratory tract samples, comprehensive clinical diagnosis should be considered ( 20 , 25 , 26 ). CSF is a sterile body fluid in normal conditions.…”

Section: Resultsmentioning

confidence: 99%

Economic impact of metagenomic next-generation sequencing versus traditional bacterial culture for postoperative central nervous system infections using a decision analysis mode: study protocol for a randomized controlled trial

Tian,

Gao,

Wang

et al. 2023

mSystems

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Central nervous system infections (CNSIs) are common complications after neurosurgery with a poor prognosis. The traditional microbiological culture methodology has a low detection rate and time consuming. Metagenomic next-generation sequencing (mNGS) has demonstrated the advantages of being faster, more accurate, and more comprehensive in clinical microbiology. Previous studies had suggested that mNGS had a high sensitivity in the diagnosis of CNSIs. Whether the application of mNGS has health economic value in clinical applications remains to be studied. We designed a prospective, single-center, superiority randomized controlled trial to compare the cost-effectiveness of mNGS with traditional methods for diagnosing CNSIs using a decision tree model. A total of 204 patients will be enrolled and randomly assigned to either the mNGS group or the traditional method group. The two groups of patients entered different decision points according to different clinical manifestations and examination results. They will be then given treatment decisions by a panel of specialists at the corresponding decision point. The primary outcome is the incremental cost-effectiveness ratio, which is the increased cost for every 1% increase in recovery rate. The secondary outcomes are a comparison of time cost, detection cost, and costs associated with antibiotics treatment between the two groups. IMPORTANCE Diagnosing and treating postoperative central nervous system infections (PCNSIs) remains challenging due to the low detection rate and time-consuming nature of traditional methods for identifying microorganisms in cerebrospinal fluid. Metagenomic next-generation sequencing (mNGS) technology provides a rapid and comprehensive understanding of microbial composition in PCNSIs by swiftly sequencing and analyzing the microbial genome. The current study aimed to assess the economic impact of using mNGS versus traditional bacterial culture-directed PCNSIs diagnosis and therapy in post-neurosurgical patients from Beijing Tiantan Hospital. mNGS is a relatively expensive test item, and whether it has the corresponding health-economic significance in the clinical application of diagnosing intracranial infection has not been studied clearly. Therefore, the investigators hope to explore the clinical application value of mNGS detection in PCNSIs after neurosurgery.

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“…2 their potential to induce lower respiratory infections, presenting new avenues for microbiological diagnostics and treatment [1]. The study illustrates the multifaceted benefits of this dataset, encompassing comprehensive microbiota characterization, identification of uncharacterized microorganisms, implications for respiratory medicine, infectious diseases, epidemiology, and public health, and its integration potential with other omics datasets.…”

mentioning

confidence: 90%

Precision Metagenomic Next-Generation Sequencing Data of Respiratory Infection

Almas,

Carpenter,

Tamrakar

et al. 2023

Preprint

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Understanding microbial composition in upper respiratory infections (URIs) is critical for effective diagnosis and treatment. Precision Metagenomic next-generation sequencing p(mNGS) can provide a comprehensive yet clinically relevant profile of respiratory infection. The hybridization capture-based targeted sequencing generated a precision metagenomics profile of 29 patients with acute URIs. Nasopharyngeal samples were collected from the subjects suspected of respiratory infection, and p(mNGS) was performed using the Illumina®/IDbyDNA Respiratory Pathogen ID/AMR Panel (RPIP). The dataset obtained from the mNGS analysis contains a wealth of information on the composition of acute URI microbiota, including the relative abundance of known pathogens and potential clinical implications. The dataset represents a valuable resource for future research endeavors in respiratory medicine, infectious disease epidemiology, and therapeutic interventions. In addition, the dataset offers significant potential for reuse and integration with other omics datasets. The comprehensive nature of the mNGS data allows the exploration of associations between the respiratory microbiota and host factors such as clinical outcomes, immune responses, or genetic predisposition. Combining this dataset with other relevant datasets, such as transcriptomics or metabolomics, could provide a deeper understanding of the complex interactions between the microbiota and the host in acute URIs.

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Deciphering Microbiota of Acute Upper Respiratory Infections: A Comparative Analysis of PCR and mNGS Methods for Lower Respiratory Trafficking Potential

Cited by 5 publications

References 83 publications

Advantage of precision metagenomics for urinary tract infection diagnostics

Advantage of precision metagenomics for urinary tract infection diagnostics

Economic impact of metagenomic next-generation sequencing versus traditional bacterial culture for postoperative central nervous system infections using a decision analysis mode: study protocol for a randomized controlled trial

Precision Metagenomic Next-Generation Sequencing Data of Respiratory Infection

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