tetano
Editor, Senior Moderator
J Comput Biol. 2016 Nov 30. [Epub ahead of print]
[h=1]Long Single-Molecule Reads Can Resolve the Complexity of the Influenza Virus Composed of Rare, Closely Related Mutant Variants.[/h] Artyomenko A[SUP]1[/SUP], Wu NC[SUP]2[/SUP], Mangul S[SUP]3,[/SUP][SUP]4[/SUP], Eskin E[SUP]3[/SUP], Sun R[SUP]5[/SUP], Zelikovsky A[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] As a result of a high rate of mutations and recombination events, an RNA-virus exists as a heterogeneous "swarm" of mutant variants. The long read length offered by single-molecule sequencing technologies allows each mutant variant to be sequenced in a single pass. However, high error rate limits the ability to reconstruct heterogeneous viral population composed of rare, related mutant variants. In this article, we present two single-nucleotide variants (2SNV), a method able to tolerate the high error rate of the single-molecule protocol and reconstruct mutant variants. 2SNV uses linkage between single-nucleotide variations to efficiently distinguish them from read errors. To benchmark the sensitivity of 2SNV, we performed a single-molecule sequencing experiment on a sample containing a titrated level of known viral mutant variants. Our method is able to accurately reconstruct clone with frequency of 0.2% and distinguish clones that differed in only two nucleotides distantly located on the genome. 2SNV outperforms existing methods for full-length viral mutant reconstruction.
[h=4]KEYWORDS:[/h] RNA viral variants; SMRT reads; single-nucleotide variation
PMID: 27901586 DOI: 10.1089/cmb.2016.0146
[PubMed - as supplied by publisher]
[h=1]Long Single-Molecule Reads Can Resolve the Complexity of the Influenza Virus Composed of Rare, Closely Related Mutant Variants.[/h] Artyomenko A[SUP]1[/SUP], Wu NC[SUP]2[/SUP], Mangul S[SUP]3,[/SUP][SUP]4[/SUP], Eskin E[SUP]3[/SUP], Sun R[SUP]5[/SUP], Zelikovsky A[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] As a result of a high rate of mutations and recombination events, an RNA-virus exists as a heterogeneous "swarm" of mutant variants. The long read length offered by single-molecule sequencing technologies allows each mutant variant to be sequenced in a single pass. However, high error rate limits the ability to reconstruct heterogeneous viral population composed of rare, related mutant variants. In this article, we present two single-nucleotide variants (2SNV), a method able to tolerate the high error rate of the single-molecule protocol and reconstruct mutant variants. 2SNV uses linkage between single-nucleotide variations to efficiently distinguish them from read errors. To benchmark the sensitivity of 2SNV, we performed a single-molecule sequencing experiment on a sample containing a titrated level of known viral mutant variants. Our method is able to accurately reconstruct clone with frequency of 0.2% and distinguish clones that differed in only two nucleotides distantly located on the genome. 2SNV outperforms existing methods for full-length viral mutant reconstruction.
[h=4]KEYWORDS:[/h] RNA viral variants; SMRT reads; single-nucleotide variation
PMID: 27901586 DOI: 10.1089/cmb.2016.0146
[PubMed - as supplied by publisher]