Comparative genomic analysis of bacteria species

National Library Of Medicine

Investigators

Linked publications, trials & patents

Abstract

The increasing prevalence of sequencing in biomedical research has provided new opportunities for biological discovery within the human microbiome. Despite the increased availability of data, identifying the underlying enzymes and species involved in many host-microbiome interactions has remained a challenging task. We aim to utilize genomic and evolutionary analyses, along with the large amount of available biological sequence data, to identify and characterize the underlying genetic and enzymatic basis of health-relevant microbial functions. Our primary focus has been on the identification and analysis of novel enzyme families associated with health-relevant microbiome functions. A major focus of our efforts this year has been our work characterizing enzyme families involved in bacterial steroid hormone metabolism. In this project, we filled a long-standing knowledge gap through the identification of a Steroid Hormone 5-Beta Reductase, revealing the underlying enzymatic basis for microbial hormone metabolism in the gut. Building from this, we analyzed the evolutionary history of this enzyme, showing that it is distinct from related bile acid reductases, and highlighting the prevalence of this and other steroid-metabolizing enzymes in human gut metagenomes. This work has resulted in a publication in Nature Communications and a collaboration with Dr. Sam Light at The University of Chicago, which has resulted in a publication that has been accepted at Cell Host and Microbe. In addition to our work on steroid metabolism, we have collaborated on multiple projects involving other metabolic functions within the gut microbiome. These include characterizations of oxidized sugar metabolism, sugar alcohols utilization, and antioxidant metabolism, which have revealed novel diversity in these functions of the microbiome. These projects have resulted in publications in Communications Biology, Nature Communications, and Cell Host and Microbe. We have also continued work on prior projects related to bilirubin reductase, building from our identification of this enzyme family to characterize the evolution and distribution of this enzyme within different animal species, highlighting species and taxa-specific evolutionary trends. This work, published in The ISME Journal, demonstrates how we can build on our previous work in identifying novel enzyme families to explore broader evolutionary trends within these families. Another focus of our work has been advancing our understanding of bacteriophage enzymes and phage-host interactions. As part of this work, we have performed an analysis of Vibrio cell surface and biofilm components, expanding our knowledge of these critical aspects of cell structure. This has resulted in a publication in mSystems and two publications currently submitted to PNAS and Science Advances. Additionally, we have collaborated on an analysis of tokenizer influence on genomic language model performance, providing a foundation for the future application of language models for identifying and analyzing genetic determinants of bacteriophage infection. Lastly, we have collaborated on multiple projects related to the analysis of bacterial nano-RNases, characterizing their activity, structure, and evolution. These collaborations have resulted in multiple projects and publications, including a manuscript with Cell Reports, and studies submitted to Science Advances and Nucleic Acids Research.