Abstract
When human samples are sequenced, many assembled contigs are “unknown”, as conventional alignments find no similarity to known sequences. Hidden Markov models (HMM) exploit the positions of specific nucleotides in protein-encoding codons in various microbes. The algorithm HMMER3 implements HMM using a reference set of sequences encoding viral proteins, “vFam”. We used HMMER3 analysis of “unknown” human sample-derived sequences and identified 510 contigs distantly related to viruses (Anelloviridae (n = 1), Baculoviridae (n = 34), Circoviridae (n = 35), Caulimoviridae (n = 3), Closteroviridae (n = 5), Geminiviridae (n = 21), Herpesviridae (n = 10), Iridoviridae (n = 12), Marseillevirus (n = 26), Mimiviridae (n = 80), Phycodnaviridae (n = 165), Poxviridae (n = 23), Retroviridae (n = 6) and 89 contigs related to described viruses not yet assigned to any taxonomic family). In summary, we find that analysis using the HMMER3 algorithm and the “vFam” database greatly extended the detection of viruses in biospecimens from humans.
Highlights
Humans are densely populated by microbes, including viruses[1, 2]
The metagenomic sequencing datasets were generated by Generation Sequencing (NGS)
The hmmsearch command from HMMER3 algorithm and the viral profile hidden Markov models (vFams) database were used to analyze a total of 6 428 566 contiguous sequences that were derived from a total of 944 human samples and classified as “unknown” by the NCBI blastn algorithm
Summary
Humans are densely populated by microbes, including viruses[1, 2]. The proportion of microbes that is viral and the composition of the metagenome seem to be altered in diseased individuals[3, 4]. It is possible that current metagenomics studies report only a fraction of the viruses that infect humans, as many novel viruses are continuously detected[5,6,7,8,9,10]. Several specific cancer forms are increased among individuals that have an impaired control of virus infections[12,13,14,15,16,17,18]. Strategies for improved detection of viruses are a high priority
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