Reference Gene Catalog for Vaginal Microbiome Biotherapeutics
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for analyzing human microbiomes, particularly the vaginal microbiome, face challenges in characterizing gene content and expression due to limitations in resources for processing massive metagenomic and metatranscriptomic datasets, and lack of comprehensive reference gene catalogs for non-gut microbiomes, hindering the development of effective live biotherapeutics.
Innovation Solution
The development of scalable reference gene catalogs that integrate functional and taxonomic characterization of metagenomic and metatranscriptomic data, using a memory-efficient network-based algorithm to cluster orthologous groups, enabling the identification of non-redundant genes and intraspecies diversity, and facilitating the formulation of targeted live biotherapeutics.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If metagenomic and metatranscriptomic sequencing is performed to characterize gene content and expression, then functional insight into microbiome roles in health and disease is improved, but computational resources and complexity increase substantially
Solution Approach 1:
The patent introduces a curated reference gene database as an intermediary between raw sequencing data and functional interpretation. This database serves as a pre-processed knowledge repository that mediates the complex computational analysis, allowing researchers to query functional information without performing exhaustive de novo assembly and annotation of entire metagenomes each time.
Solution Approach 2:
The reference gene database is constructed in advance through preliminary curating, annotating, and organizing of gene sequences and functional information from multiple sources. This preliminary action creates a ready-to-use resource that eliminates the need for repeated computational-intensive processing during actual microbiome studies.
2Measurement precision
If 16S rRNA gene sequencing is used for taxonomic profiling, then species-level identification is achieved, but functional gene content and metabolic capabilities remain unknown
Solution Approach 1:
The patent merges taxonomic identification capabilities with functional gene content analysis by integrating data from multiple sequencing approaches (16S rRNA gene sequencing, metagenomic sequencing, and metatranscriptomic sequencing) into a unified reference database framework. This allows simultaneous retrieval of both taxonomic and functional information.
Solution Approach 2:
The reference gene database serves multiple functions: it provides taxonomic identification, functional annotation, metabolic pathway reconstruction, and strain-level differentiation. This multi-functional resource replaces the need for separate specialized databases and analysis pipelines.
3Loss of information
If comprehensive metagenomic datasets are analyzed to discover gene-specific health outcomes, then understanding of microbiome function is improved, but lack of curated reference resources limits analysis accuracy
Solution Approach 1:
The curated reference gene database acts as an intermediary that standardizes and validates functional annotations across different studies. By providing a centralized, expert-curated resource, it mediates between raw sequencing data and reliable functional interpretation, improving analysis accuracy through consistent annotation standards.
4Loss of information
If de novo assembly of metagenomic datasets is performed, then complete genomic information is obtained, but computational time and memory requirements increase substantially
Solution Approach 1:
Instead of performing de novo assembly for each new metagenomic dataset, the patent creates a reference copy database from assembled genomic information obtained from multiple sources. Researchers can then map new sequencing reads against this pre-assembled reference copy, obtaining genomic completeness information much faster without repeating the computationally intensive assembly process.
Data Source
AI summary
Methods of formulating live biotherapeutics are disclosed in which a deficiency or excess of a specific bacterial strain in a person's microbiome is identified by comparing a gene-specific characterization of the person's microbiome against a comprehensive, non-redundant reference gene catalog, and the biotherapeutic is formulated by selecting bacteria to address the deficiency or excess. Embodiments include the formulation of live biotherapeutics for improving the health of a person's vaginal microbiome, i.e. using a vaginal reference gene catalog, and may be suitable for ameliorating, treating, or preventing a malignancy such as a cancer of the female genitourinary system.