The effect of variant interference on de novo assembly for viral deep sequencing.
BMC Genomics
; 21(1): 421, 2020 Jun 22.
Article
em En
| MEDLINE
| ID: mdl-32571214
ABSTRACT
BACKGROUND:
Viruses have high mutation rates and generally exist as a mixture of variants in biological samples. Next-generation sequencing (NGS) approaches have surpassed Sanger for generating long viral sequences, yet how variants affect NGS de novo assembly remains largely unexplored.RESULTS:
Our results from > 15,000 simulated experiments showed that presence of variants can turn an assembly of one genome into tens to thousands of contigs. This "variant interference" (VI) is highly consistent and reproducible by ten commonly-used de novo assemblers, and occurs over a range of genome length, read length, and GC content. The main driver of VI is pairwise identities between viral variants. These findings were further supported by in silico simulations, where selective removal of minor variant reads from clinical datasets allow the "rescue" of full viral genomes from fragmented contigs.CONCLUSIONS:
These results call for careful interpretation of contigs and contig numbers from de novo assembly in viral deep sequencing.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Vírus
/
Biologia Computacional
/
Mutação
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
BMC Genomics
Assunto da revista:
GENETICA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos