Sequence-based diagnostics and precision medicine in bacterial and viral infections: from bench to bedside

Abstract

Purpose of review Nucleic acid sequence-based organism identification plays an important role in the diagnosis and management of transplant and cancer-associated infectious diseases. Here, we provide a high-level overview of advanced sequencing technologies, discuss test performance, and highlight unmet research needs with a focus on immunocompromised hosts. Recent findings Next-generation sequencing (NGS) technologies are powerful tools with a growing role in managing immunocompromised patients with suspected infection. Targeted NGS (tNGS) can identify pathogens directly from patient specimens, especially for mixed samples, and has been used to detect resistance mutations in transplant-related viruses (e.g. CMV). Whole-genome sequencing (WGS) is increasingly used for outbreak investigations and infection control. Metagenomic NGS (mNGS) is useful for hypothesis-free testing and can simultaneously assess pathogens and host response to infection. Summary NGS testing increases diagnostic yield relative to standard culture and Sanger sequencing but may be limited by high cost, turnaround times, and detection of unexpected organisms or commensals of uncertain significance. Close collaboration with the clinical microbiology laboratory and infectious diseases is recommended when NGS testing is considered. Additional research is required to understand which immunocompromised patients are most likely to benefit from NGS testing, and when testing should ideally be performed.

Human Cytomegalovirus (HCMV) Genetic Diversity, Drug Resistance Testing and Prevalence of the Resistance Mutations: A Literature Review

“…Standardization of the method and diagnostic utility in comparison with traditional Sanger sequencing remains to be completed, but NGS is a powerful tool with a growing role in managing immunocompromised patients with suspected infection and is recommended for use in clinical trials. NGS can also provide data on the HCMV genotypes circulating in the population, which may facilitate the development of vaccines and immunobiological preparations, enable dynamic monitoring of risk groups (pregnant, newborns, children of the first year of life and patients who underwent solid organ transplantation), predict the epidemiological situation for cytomegalovirus infection, and improve the system of epidemiological surveillance of infections in general [ 59 , 60 ].…”

mRNA and Adenoviral Vector Vaccine Platforms Utilized in COVID-19 Vaccines: Technologies, Ecosystem, and Future Directions

“…The sequence encoding an antigen can be easily designed once the genome sequence of the pathogen is identified, and various antigen sequences can be tested [ 67 ]. Currently, a whole genome sequencing of a virus is possible within a short time, owing to progress in next-generation sequencers [ 68 ]. For these reasons, viral vector vaccines have been highly anticipated as a vaccine technology that induces a strong immune response, is safe, and enables rapid and simultaneous vaccine development.…”