Observational studies on the gut microbiome have firmly established that the human gut microbiome affects health, disease, and response to treatments. However, the current analysis methods available for whole-genome shotgun (WGS) microbiome data does not effectively identify the underlying causal mechanisms, which are the critical next step to translate microbiome science into novel therapies. Moreover, existing gene-level metagenomics methods have been limited by the high dimensionality of the data generated.
To address the limitations of current approaches, Dr. Samuel Minot has developed geneshot – a novel bioinformatics tool for identifying testable hypotheses based on gene-level metagenomic analysis of whole genome sequencing microbiome data. The high dimensionality issue of microbial protein-coding genes is solved by identifying the groups of genes with correlated levels of relative abundance across specimens (co-abundant gene groups). By applying geneshot to two independent cohorts, Dr. Minot was able to identify taxa and strain-specific genomic islands consistently associated with response to immune checkpoint inhibitor -based cancer treatment. Furthermore, geneshot identified specific possible mechanisms of action (type II secretion, TonB-dependent transport, and phage) that are potential novel strategies for intervention.
- Human microbiome diagnostic and therapeutic development
- Identifying microbial correlates of efficacy from clinical trials
- Linking bacterial isolate libraries to microbiome signatures from treatment/control comparisons
- Applications in infectious diseases, cancers, gastrointestinal disorders, metabolic diseases and other diseases
- In contrast to other end-to-end pipelines, the unit of analysis that underlies geneshot is de novo assembled protein-coding gene sequences, which are dimension-reduced via co-abundance clustering;
- Reduces reliance on reference databases (which are often incomplete) or inaccurate ontological hierarchies;
- Uses the Nextflow workflow management system to provide a convenient mechanism for microbiome analysis; can be implemented across a variety of high-performance computing infrastructures (SLURM, PBS, AWS, GCP, etc.) with minimal configuration required for each user.
US Patent Application No. 17/225,991
The global microbiome market reached a value of nearly $4.5B in 2020 and is increasing at a compound annual growth rate (CAGR) of 12.6% since 2015. The market is expected to grow at a CAGR of 12.7% from 2020 to reach $9B in 2025.
- Samuel Minot, Ph.D., Staff Scientist, Microbiome Research Initiative, Vaccine and Infectious Disease Division