INTEGRATED HOST-MICROBE METAGENOMICS OF CELL-FREE NUCLEIC ACID FOR SEPSIS DIAGNOSIS

INTEGRATED HOST-MICROBE METAGENOMICS OF CELL-FREE NUCLEIC ACID FOR SEPSIS DIAGNOSIS

Researchers at UCSF and the Chan Zuckerberg Institute have developed a single-sample metagenomic approach combining host transcriptional profiling with unbiased pathogen detection to improve sepsis diagnosis.

Sepsis causes 20% of all deaths globally and contributes to 20-50% of hospital deaths in the United States. Early diagnosis and identification of the etiologic pathogen are necessary factors for timely and appropriate antibiotic therapy administration and are critical for sepsis survival. However in over 30% of cases, no etiologic pathogen is identified, demonstrating limitations of current microbiologic diagnostics. An additional confounding factor is that the existing tests cannot effectively differentiate sepsis from non-infectious systemic illnesses, which often present in clinically similar fashions at the time of hospital admission. As a result, antibiotic treatment often remains empiric rather than targeted toward specific pathogens, with clinical decision making based on epidemiological data rather than individual patient data. This approach leads to antimicrobial overuse and misuse, contributing to treatment failures, opportunistic infections and the emergence of drug-resistant organisms.

Stage of Research

The inventors have developed a single-sample metagenomic approach combining host transcriptional profiling with unbiased pathogen detection to improve lower respiratory tract infection diagnosis; sepsis provides an additional application of their integrated host-microbe metagenomics approach.

Applications

Predicting the likelihood of “general” sepsis by determining the expression profile of a panel of host genes that undergo quantitative changes in sepsis.
Predicting the likelihood of viral sepsis based on transcriptional profiling of cell free RNA of host marker genes.
Determination of sepsis risk based on microbial mass and detection of a dominant pathogen based on cell free DNA analysis from a plasma or serum sample.

Advantages

Introduction of culture-independent methods including metagenomic next generation sequencing (mNGS) and plasma cell-free DNA sequencing enables minimally invasive detection of circulating pathogen nucleic acid originating from diverse sites of infection.
Integrating host transcriptomic profiling and broad-range metagenomic pathogen detection from nucleic acid is a promising new tool for sepsis diagnosis.

Stage of Development

Research – in vitro

Publications

Kalantar KL, Langelier CR, et al., Integrated host-microbe plasma metagenomics for sepsis diagnosis in a prospective cohort of critically ill adults. Nature microbiology 2022. PMID: 36266337