Abstract

SummarySpacePHARER (CRISPR Spacer Phage–Host Pair Finder) is a sensitive and fast tool for de novo prediction of phage–host relationships via identifying phage genomes that match CRISPR spacers in genomic or metagenomic data. SpacePHARER gains sensitivity by comparing spacers and phages at the protein level, optimizing its scores for matching very short sequences, and combining evidence from multiple matches, while controlling for false positives. We demonstrate SpacePHARER by searching a comprehensive spacer list against all complete phage genomes.Availability and implementationSpacePHARER is available as an open-source (GPLv3), user-friendly command-line software for Linux and macOS: https://github.com/soedinglab/spacepharer.Supplementary information Supplementary data are available at Bioinformatics online.

Highlights

  • Viruses of bacteria and archaea are the most abundant biological entities in nature

  • To increase sensitivity, (1) we compare protein instead of nucleotide sequences because phage genomes are mostly coding, and, to evade the Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) immune response, they are under pressure to mutate their nucleotides with minimal change on the amino acid level

  • Phage genomes are supplied as separate FASTA files or can be downloaded by SpacePHARER from NCBI GenBank [2]

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Summary

Introduction

Viruses of bacteria and archaea (phages) are the most abundant biological entities in nature. After surviving a phage infection, they incorporate a short DNA fragment (3238 nt) as a spacer in a CRISPR array. Some CRISPR-Cas systems require a 2-6 nucleotide long, highly conserved protospacer-adjacent motif (PAM) flanking the viral target to prevent autoimmunity.

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