From simple to complex: Protein-based biomarker discovery in tuberculosis.

Tuberculosis (TB) is a deadly infectious disease that affects millions of people globally. TB proteomics signature discovery has been a rapidly growing area of research that aims to identify protein biomarkers for the early detection, diagnosis, and treatment monitoring of TB. In this review, we have highlighted recent advances in this field and how it is moving from the study of single proteins to high-throughput profiling and from only using proteomics to include additional types of data in multi-omics studies. We have further covered the different sample types and experimental technologies used in TB proteomics signature discovery, focusing on studies of HIV-negative adults. The published signatures were defined as either coming from hypothesis-based protein targeting or from unbiased discovery approaches. The methodological approaches influenced the type of proteins identified and were associated with the circulating protein abundance. However, both approaches largely identified proteins involved in similar biological pathways, including acute-phase responses and T-helper type 1 and type 17 responses. By analysing the frequency of proteins in the different signatures, we could also highlight potential robust biomarker candidates. Finally, we discuss the potential value of integration of multi-omics data and the importance of control cohorts and signature validation.