CAMMiQ

CAMMiQ identifies and quantifies microbial species and strains from high-throughput sequencing (HTS) reads to estimate microbial abundance.

Key Features:

• Combinatorial approach: Utilizes arbitrary-length, doubly-unique substrings (substrings found in exactly two genomes) to improve specificity of read classification between closely related strains.
• Efficient indexing and query resolution: Constructs a compact index of sparsified subsets of the shortest unique and doubly-unique substrings from each genome to manage large genomic databases, including bacterial and viral genomes from NCBI RefSeq.
• Combinatorial optimization: Employs a combinatorial optimization formulation to resolve ambiguities associated with doubly-unique substrings during read assignment and abundance estimation.
• Species- and strain-level quantification: Estimates relative abundance at both species and strain resolution from HTS reads.
• Compatibility with scRNA-seq: Distinguishes closely related microbial strains in single-cell RNA sequencing (scRNA-seq) data, including separately infected Salmonella strains.
• Performance and resource efficiency: Demonstrates superior accuracy on simulated and real datasets, including complex bacterial genomes, while maintaining computational efficiency comparable to other tools.

Scientific Applications:

• Microbiome studies: Determining composition and dynamics of microbial communities within environments or host organisms.
• Infectious disease research: Identifying pathogenic strains and quantifying their prevalence and distribution.
• Genomic epidemiology: Tracking the spread and evolution of microbial strains in populations.

Methodology:

Builds a compact index from unique and doubly-unique substrings within user-specified length ranges using sparsified subsets of the shortest unique and doubly-unique substrings per genome, then resolves queries by identifying genomic origins of HTS reads and estimating relative abundances via a combinatorial optimization formulation to disambiguate doubly-unique substring assignments.