Deciphering bacterial protein functions with innovative computational methods

Bacteria colonize every niche on Earth and play key roles in many environmental and host-associated processes. The sequencing revolution revealed the remarkable bacterial genetic and proteomic diversity and the genomic content of cultured and uncultured bacteria. However, deciphering functions of novel proteins remains a high barrier, often preventing the deep understanding of microbial life and its interaction with the surrounding environment. In recent years, exciting new bioinformatic tools, many of which are based on machine learning, facilitate the challenging task of gene and protein function discovery in the era of big genomics data, leading to the generation of testable hypotheses for bacterial protein functions. The new tools allow prediction of protein structures and interactions and allow sensitive and efficient sequence- and structure-based searching and clustering. Here, we summarize some of these recent tools which revolutionize modern microbiology research, along with examples for their usage, emphasizing the user-friendly, web-based ones. Adoption of these capabilities by experimentalists and computational biologists could save resources and accelerate microbiology research.