High-resolution strain-level microbiome composition analysis from short reads

Abstract Background Bacterial strains under the same species can exhibit different biological properties, making strain-level composition analysis an important step in understanding the dynamics of microbial communities. Metagenomic sequencing has become the major means for probing the microbial composition in host-associated or environmental samples. Although there are a plethora of composition analysis tools, they are not optimized to address the challenges in strain-level analysis: highly similar strain genomes and the presence of multiple strains under one species in a sample. Thus, this work aims to provide a high-resolution and more accurate strain-level analysis tool for short reads. Results In this work, we present a new strain-level composition analysis tool named StrainScan that employs a novel tree-based k -mers indexing structure to strike a balance between the strain identification accuracy and the computational complexity. We tested StrainScan extensively on a large number of simulated and real sequencing data and benchmarked StrainScan with popular strain-level analysis tools including Krakenuniq, StrainSeeker, Pathoscope2, Sigma, StrainGE, and StrainEst. The results show that StrainScan has higher accuracy and resolution than the state-of-the-art tools on strain-level composition analysis. It improves the F1 score by 20% in identifying multiple strains at the strain level. Conclusions By using a novel k -mer indexing structure, StrainScan is able to provide strain-level analysis with higher resolution than existing tools, enabling it to return more informative strain composition analysis in one sample or across multiple samples. StrainScan takes short reads and a set of reference strains as input and its source codes are freely available at https://github.com/liaoherui/StrainScan .