PhageLeads: Rapid Assessment of Phage Therapeutic Suitability Using an Ensemble Machine Learning Approach

Viruses

Ravichandran Manickam¹  Kasi Marimuthu¹  Sivachandran Parimannan¹  Bent Petersen¹  Thomas Sicheritz-Pontén¹  Kumarasan Yukgehnaish¹  Heera Rajandas¹  Martha R. J. Clokie²  Andrew Millard² 

[1] Center of Excellence for Omics-Driven Computational Biodiscovery (COMBio), AIMST University, Bedong 08100, Kedah, Malaysia;Department Genetics and Genome Biology, University of Leicester, Leicester LE1 7RH, UK;

关键词: phage therapy;    AMR;    lysogeny;    machine learning;    genomics;   

DOI  :  10.3390/v14020342

来源: DOAJ

【 摘 要 】

The characterization of therapeutic phage genomes plays a crucial role in the success rate of phage therapies. There are three checkpoints that need to be examined for the selection of phage candidates, namely, the presence of temperate markers, antimicrobial resistance (AMR) genes, and virulence genes. However, currently, no single-step tools are available for this purpose. Hence, we have developed a tool capable of checking all three conditions required for the selection of suitable therapeutic phage candidates. This tool consists of an ensemble of machine-learning-based predictors for determining the presence of temperate markers (integrase, Cro/CI repressor, immunity repressor, DNA partitioning protein A, and antirepressor) along with the integration of the ABRicate tool to determine the presence of antibiotic resistance genes and virulence genes. Using the biological features of the temperate markers, we were able to predict the presence of the temperate markers with high MCC scores (>0.70), corresponding to the lifestyle of the phages with an accuracy of 96.5%. Additionally, the screening of 183 lytic phage genomes revealed that six phages were found to contain AMR or virulence genes, showing that not all lytic phages are suitable to be used for therapy. The suite of predictors, PhageLeads, along with the integrated ABRicate tool, can be accessed online for in silico selection of suitable therapeutic phage candidates from single genome or metagenomic contigs.

【 授权许可】

Unknown