Viruses make up the most abundant biological entities on the planet, but the high levels of variability between viral sequences and lack of known hosts have left a large majority of these sequences undocumented using traditional laboratory techniques. Through metagenomic sampling and computational analysis, it is now possible for DNA sequences to be isolated and identified as phages. This was proven in the 2014 discovery of crAssphage, a highly abundant bacteriophage present in the majority of human guts. The amount of publicly available sequencing data since then has grown exponentially, and there are now over 4,000 human fecal metagenomes available on the Sequence Read Archive (SRA). We developed a computational pipeline to extract data from the SRA, perform a cross-assembly, identify abundant, co-occurring contigs, and sort these contigs into genome bins. The contigs contained in these genome bins can then be compared to a database of all documented phage genes to date. All of the metagenomes in the SRA can then be scanned for this collection of contigs, and runs containing the contigs most similar to phage genes are repeatedly put through the pipeline. This method exploits the fact that contigs belonging to the same phage-like entity will occur together, and cross assembly of runs containing the largest abundance of such contigs should reveal the complete genome. These methods are promising for the discovery of novel phages in the human gut, which can improve our knowledge of human health.
