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Streamlining CRISPR spacer-based bacterial host predictions to decipher the viral dark matter.

ABSTRACT: Thousands of new phages have recently been discovered thanks to viral metagenomics. These phages are extremely diverse and their genome sequences often do not resemble any known phages. To appreciate their ecological impact, it is important to determine their bacterial hosts. CRISPR spacers can be used to predict hosts of unknown phages, as spacers represent biological records of past phage-bacteria interactions. However, no guidelines have been established to standardize host prediction based on CRISPR spacers. Additionally, there are no tools that use spacers to perform host predictions on large viral datasets. Here, we developed a set of tools that includes all the necessary steps for predicting the hosts of uncharacterized phages. We created a database of >11 million spacers and a program to execute host predictions on large viral datasets. Our host prediction approach uses biological criteria inspired by how CRISPR-Cas naturally work as adaptive immune systems, which make the results easy to interpret. We evaluated the performance using 9484 phages with known hosts and obtained a recall of 49% and a precision of 69%. We also found that this host prediction method yielded higher performance for phages that infect gut-associated bacteria, suggesting it is well suited for gut-virome characterization.

SUBMITTER: Dion MB

PROVIDER: S-EPMC8034630 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:In the late 20th century, cosmology became a precision science. Now, at the beginning of the next century, the parameters describing how our universe evolved from the Big Bang are generally known to a few percent. One key parameter is the total mass density of the universe. Normal matter constitutes only a small fraction of the total mass density. Observations suggest this additional mass, the dark matter, is cold (that is, moving nonrelativistically in the early universe) and interacts feebly if at all with normal matter and radiation. There's no known such elementary particle, so the strong presumption is the dark matter consists of particle relics of a new kind left over from the Big Bang. One of the most important questions in science is the nature of this dark matter. One attractive particle dark-matter candidate is the axion. The axion is a hypothetical elementary particle arising in a simple and elegant extension to the standard model of particle physics that nulls otherwise observable CP-violating effects (where CP is the product of charge reversal C and parity inversion P) in quantum chromo dynamics (QCD). A light axion of mass 10(-(6-3)) eV (the invisible axion) would couple extraordinarily weakly to normal matter and radiation and would therefore be extremely difficult to detect in the laboratory. However, such an axion is a compelling dark-matter candidate and is therefore a target of a number of searches. Compared with other particle dark-matter candidates, the plausible range of axion dark-matter couplings and masses is narrowly constrained. This focused search range allows for definitive searches, where a nonobservation would seriously impugn the dark-matter QCD-axion hypothesis. Axion searches use a wide range of technologies, and the experiment sensitivities are now reaching likely dark-matter axion couplings and masses. This article is a selective overview of the current generation of sensitive axion searches. Not all techniques and experiments are discussed, but I hope to give a sense of the current experimental landscape of the search for dark-matter axions.

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Streamlining CRISPR spacer-based bacterial host predictions to decipher the viral dark matter.

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