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Gene-level Metagenomic Analysis to enable Human Microbiome Therapeutic and Diagnostic Development

An end-to-end bioinformatic microbiome analysis tool using co-abundant gene groups to probe high-dimensional shotgun metagenomic data sets

  • Stage: Code fully developed and validated
  • Type: Research Tool
  • Categories: IT / Software

Technology Overview

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.

Applications

  • 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

Advantages

  • 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.

Patent Information

US Patent Application No. 17/225,991

Market Overview

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.

Investigator Overview

  • Samuel Minot, Ph.D., Staff Scientist, Microbiome Research Initiative, Vaccine and Infectious Disease Division
Tech ID: 20-117
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