Precision Metagenomics: Rapid Metagenomic Analyses for Infectious Disease Diagnostics and Public Health Surveillance.
Next-generation sequencing (NGS) technologies have ushered in the era of precision medicine, transforming the way we treat cancer patients and diagnose disease. Concomitantly, the advent of these technologies has created a surge of microbiome and metagenomic studies over the last decade, many of which are focused on investigating the host-gene-microbial interactions responsible for the development and spread of infectious diseases, as well as delineating their key role in maintaining health. As we continue to discover more information about the etiology of infectious diseases, the translational potential of metagenomic NGS methods for treatment and rapid diagnosis is becoming abundantly clear. Here, we present a robust protocol for the implementation and application of "precision metagenomics" across various sequencing platforms for clinical samples. Such a pipeline integrates DNA/RNA extraction, library preparation, sequencing, and bioinformatics analyses for taxonomic classification, antimicrobial resistance (AMR) marker screening, and functional analysis (biochemical and metabolic pathway abundance). Moreover, the pipeline has 3 tracks: STAT for results within 24 h; Comprehensive that affords a more in-depth analysis and takes between 5 and 7 d, but offers antimicrobial resistance information; and Targeted, which also requires 5-7 d, but with more sensitive analysis for specific pathogens. Finally, we discuss the challenges that need to be addressed before full integration in the clinical setting.
Department of Physiology and Biophysics, Weill Cornell Medicine, New York, New York 10065, USA;; The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, New York, New York 10021, USA;; School of Medicine, New York Medical College, Valhalla, New York 10595, USA.
Ebrahim
E
Afshinnekoo
Department of Physiology and Biophysics, Weill Cornell Medicine, New York, New York 10065, USA;; The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, New York, New York 10021, USA.
Chou
C
Chou
Department of Physiology and Biophysics, Weill Cornell Medicine, New York, New York 10065, USA;; The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, New York, New York 10021, USA.
Noah
N
Alexander
Department of Physiology and Biophysics, Weill Cornell Medicine, New York, New York 10065, USA;; The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, New York, New York 10021, USA.
Sofia
S
Ahsanuddin
Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota 55905, USA; and.
Audrey N
AN
Schuetz
Department of Physiology and Biophysics, Weill Cornell Medicine, New York, New York 10065, USA;; The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, New York, New York 10021, USA;; Feil Family Brain & Mind Research Institute, New York, New York 10065, USA.
Christopher E
CE
Mason
D003141:Communicable Diseases / Q000175:diagnosis* / Q000382:microbiology; D019295:Computational Biology; D015723:Gene Library; D059014:High-Throughput Nucleotide Sequencing / Q000592:standards; D006801:Humans; D056186:Metagenomics / Q000592:standards*; D057285:Precision Medicine / Q000592:standards; D062486:Public Health Surveillance; D012015:Reference Standards; D017422:Sequence Analysis, DNA; D057170:Translational Research, Biomedical
antimicrobial resistance; microbiome; next-generation sequencing; pathogen detection