StrainIQ: A Novel -Gram-Based Method for Taxonomic Profiling of Human Microbiota at the Strain Level

The emergence of next-generation sequencing (NGS) technology has greatly influenced microbiome research and led to the development of novel bioinformatics tools to deeply analyze metagenomics datasets. Identifying strain-level variations in microbial communities is important to understanding the onset and progression of diseases, host-pathogen interrelationships, and drug resistance, in addition to designing new therapeutic regimens. In this study, we developed a novel tool called StrainIQ (strain identification and quantification) based on a new -gram-based (series of number of adjacent nucleotides in the DNA sequence) algorithm for predicting and quantifying strain-level taxa from whole-genome metagenomic sequencing data. We thoroughly evaluated our method using simulated and mock metagenomic datasets and compared its performance with existing methods. On average, it showed 85.8% sensitivity and 78.2% specificity on simulated datasets. It also showed higher specificity and sensitivity using -gram models built from reduced reference genomes and on models with lower coverage sequencing data. It outperforms alternative approaches in genus- and strain-level prediction and strain abundance estimation. Overall, the results show that StrainIQ achieves high accuracy by implementing customized model-building and is an efficient tool for site-specific microbial community profiling.