Liquid biopsy for infectious diseases: a focus on microbial cell-free DNA sequencing

Metagenomic next-generation sequencing (mNGS) of microbial cell-free DNA (mcfDNA sequencing) is becoming an attractive diagnostic modality for infectious diseases, allowing broad-range pathogen detection, noninvasive sampling, and rapid diagnosis. At this key juncture in the translation of metagenomics into clinical practice, an integrative perspective is needed to understand the significance of emerging mcfDNA sequencing technology. In this review, we summarized the actual performance of the mcfDNA sequencing tests recently used in health care settings for the diagnosis of a variety of infectious diseases and further focused on the practice considerations (challenges and solutions) for improving the accuracy and clinical relevance of the results produced by this evolving technique. Such knowledge will be helpful for physicians, microbiologists and researchers to understand what is going on in this quickly progressing field of non-invasive pathogen diagnosis by mcfDNA sequencing and promote the routine implementation of this technique in the diagnosis of infectious disease.