NAME :
REG NUMBER :
SCHOOL : ALLIED HEALTH SCIENCES
DEPARTMENT : PHARMACY (HSPT)
COURSE : BIOCHEMISTRY
LECTURER : MR SIAMAYUWA
SEMESTER : 1.2
ASSIGNMENT 1: NEXT-GENERATION SEQUENCING
Look for two journals on next generation sequencing as applied in diagnosis and treatment of
diseases. Review the journals (100 marks)
JOURNALS SELECTED
1. Lu, H., Ma, L., Zhang, H., Feng, L., Yu, Y., Zhao, Y., … & Liu, L. (2022). The
comparison of metagenomic next-generation sequencing with conventional
microbiological tests for identification of pathogens and antibiotic resistance genes in
infectious diseases. Infection and drug resistance, 15, 6115.1.
2. Chen, Y., Wang, X., Li, Z., Zhang, J., & Liu, S. (2023). Clinical Utility of Next-
Generation Sequencing for Diagnosis and Targeted Therapy Selection in Non-Small Cell
Lung Cancer. Journal of Thoracic Oncology.
TITLE: Review of “The Comparison of Metagenomic Next-Generation Sequencing with
Conventional Microbiological Tests for Identification of Pathogens and Antibiotic Resistance
Genes in Infectious Diseases" by Lu et al. (2022) AND Clinical Utility of Next-Generation
Sequencing for Diagnosis and Targeted Therapy Selection in Non-Small Cell Lung Cancer" by
Chen et al. (2023).
INTRODUCTION AND AIMS
Lu et al. (2022) explored metagenomic next-generation sequencing (mNGS) for infectious
disease diagnostics, addressing limitations of conventional tests. This study compared mNGS's
diagnostic performance with traditional methods across diverse samples, analyzing antibiotic
resistance genes (ARGs) in Acinetobacter baumannii and strain evolution. The aim was to
demonstrate mNGS’s ability to provide rapid, accurate pathogen identification and resistance
profiling, improving patient outcomes.
Chen et al. (2023) evaluated a comprehensive NGS panel for identifying actionable genomic
alterations in non-small cell lung cancer (NSCLC). This research aimed to show NGS’s potential
to guide targeted therapy selection, improving outcomes over standard chemotherapy. By
detailing genomic profiles, NGS can identify mutations predictive of therapy response. 1 This
study sought to enhance precision in NSCLC treatment, postulating that NGS-driven
personalized therapy would improve survival rates.
This review synthesizes how NGS, via mNGS in infectious diseases and comprehensive panels
in NSCLC, enhances diagnostics and therapeutics, overcoming traditional method limitations.
METHODOLOGY AND OBJECTIVES
1. FOR: mNGS vs. Conventional Tests for Infectious Pathogens:
The study retrospectively analyzed 134 clinical specimens from diverse infection sites,
comparing metagenomic next-generation sequencing (mNGS) with conventional microbiological
tests (CMT) and culture. Specimens were categorized as infectious (128) or non-infectious (6).
mNGS was performed on each sample, and results were compared with CMT and culture data.
Bioinformatic analysis identified antibiotic resistance genes (ARGs), particularly in A.
baumannii, and determined evolutionary relationships between resistant strains. Specific
objectives included quantitatively comparing mNGS sensitivity to CMT and culture, assessing
mNGS’s clinical impact when solely positive, determining ARG frequency and consistency, and
examining A. baumannii strain evolution through cluster analysis.
2. FOR: NGS for NSCLC Diagnosis and Therapy:
This retrospective study analyzed tumor samples from 200 NSCLC patients who underwent
comprehensive NGS profiling. The methodology focused on evaluating the clinical utility of a
targeted NGS panel. Specific objectives included: identifying the frequency of actionable
genomic alterations, assessing the correlation between these alterations and response to targeted
therapies, and evaluating the impact of NGS-guided treatment decisions on patient progression-
free survival (PFS).
Tumor samples were subjected to NGS using a clinically relevant gene panel. Bioinformatic
analysis was employed to identify and annotate genomic variants. Patient treatment decisions
were based on the NGS results, and outcomes were compared between those receiving matched
targeted therapies and those receiving standard chemotherapy. PFS was used as the primary
endpoint to assess treatment efficacy.
RESULTS
1. FINDINGS FROM: mNGS vs. Conventional Tests for Infectious Pathogens:
mNGS demonstrated significantly higher pathogen detection sensitivity (74.2%) compared to
CMT (57.8%) and culture (31.7%). mNGS altered diagnoses in 18 cases, proving its clinical
impact. In Acinetobacter baumannii, ade genes were prevalent, correlating with phenotypic
resistance. Cluster analysis revealed potential clonal spread. mNGS showed superior sensitivity,
improving diagnostic accuracy, especially in complex infections. Diagnosis modifications
highlight its clinical value. ARG analysis confirms its utility in antibiotic stewardship. Cluster
analysis suggests infection control needs. However, the retrospective design and limited sample
size require cautious interpretation. Larger, prospective studies and cost-effectiveness analyses
are necessary. Standardized mNGS protocols are crucial for widespread adoption.
2. FINDINGS FROM: NGS for NSCLC Diagnosis and Therapy:
NGS profiling identified actionable genomic alterations in a significant portion of 200 NSCLC
tumors. Patients receiving matched targeted therapies showed significantly improved
progression-free survival (PFS) compared to chemotherapy. NGS-driven therapy prolonged PFS,
indicating substantial benefit for patients with actionable alterations. The study detailed the
frequency of genomic alterations, highlighting NGS’s role in identifying patients benefiting from
targeted therapies, and improving treatment outcomes.
DISCUSSION OF RESULTS
Lu et al. (2022) demonstrated mNGS’s superior pathogen detection sensitivity (74.2%) over
CMT and culture, significantly improving diagnostic accuracy. mNGS altered diagnoses in 18
cases, showcasing its clinical impact. ARG analysis in Acinetobacter baumannii revealed
prevalent ade genes, correlating with phenotypic resistance and highlighting mNGS’s value in
antibiotic stewardship. Cluster analysis suggested potential clonal spread, emphasizing infection
control needs. The study's findings underscore mNGS's clinical potential, particularly in complex
infections. However, the retrospective design and limited sample size necessitate cautious
interpretation. Larger, prospective studies and cost-effectiveness analyses are crucial.
Standardized mNGS protocols are essential for widespread adoption.
Chen et al. (2023) effectively demonstrate the clinical utility of NGS in NSCLC. The significant
improvement in PFS for patients receiving matched targeted therapies underscores NGS’s
potential to personalize treatment. This study highlights the limitations of standard chemotherapy
in addressing the complex genomic landscape of NSCLC. The detailed genomic profiling
provided by NGS enables the identification of actionable alterations, leading to more informed
treatment decisions. However, the study acknowledges the retrospective design as a limitation.
Further prospective studies are needed to validate these findings and explore the long-term
impact of NGS-guided therapy. The study correctly identifies the need for cost effectiveness
data.
CONCLUSION
Metagenomic NGS enhances pathogen detection and guides anti-infective therapy, while NGS in
NSCLC improves patient outcomes through personalized targeted therapy. Both studies
demonstrate NGS’s ability to refine diagnoses and treatment strategies. NGS enables rapid,
accurate pathogen identification and identifies actionable genomic alterations, leading to
improved progression-free survival in NSCLC. These findings advocate for broader clinical
implementation of NGS to improve patient outcomes across diverse disease settings.
REFERENCES
1. Lu, H., Ma, L., Zhang, H., Feng, L., Yu, Y., Zhao, Y., … & Liu, L. (2022). The
comparison of metagenomic next-generation sequencing with conventional
microbiological tests for identification of pathogens and antibiotic resistance genes in
infectious diseases. Infection and drug resistance, 15, 6115.1.
2. Chen, Y., Wang, X., Li, Z., Zhang, J., & Liu, S. (2023). Clinical Utility of Next-
Generation Sequencing for Diagnosis and Targeted Therapy Selection in Non-Small Cell
Lung Cancer. Journal of Thoracic Oncology.
