Influenza classification from short reads with VAPOR facilitates robust mapping pipelines and zoonotic strain detection for routine surveillance applications.

Joel A Southgate,Thomas R Connor,Matthew J Bull,Joanne Watkins,Benjamin Southgate,Clare M Brown,Catherine Moore,Sally Corden,Inanc Birol

doi:10.1093/bioinformatics/btz814

Abstract

MotivationInfluenza viruses represent a global public health burden due to annual epidemics and pandemic potential. Due to a rapidly evolving RNA genome, inter-species transmission, intra-host variation, and noise in short-read data, reads can be lost during mapping, and de novo assembly can be time consuming and result in misassembly. We assessed read loss during mapping and designed a graph-based classifier, VAPOR, for selecting mapping references, assembly validation and detection of strains of non-human origin.ResultsStandard human reference viruses were insufficient for mapping diverse influenza samples in simulation. VAPOR retrieved references for 257 real whole-genome sequencing samples with a mean of identity to assemblies, and increased the proportion of mapped reads by up to 13.3% compared to standard references. VAPOR has the potential to improve the robustness of bioinformatics pipelines for surveillance and could be adapted to other RNA viruses.Availability and implementationVAPOR is available at https://github.com/connor-lab/vapor.Supplementary information Supplementary data are available at Bioinformatics online.

Highlights

Influenza viruses are enveloped, single-stranded, segmented negative-sense RNA viruses of the family Orthomyxoviridae
We aim to show that this problem can be resolved by classification of isolates from reads prior to analysis by directly querying a De Bruijn graph (DBG) built directly from Illumina sequencing reads
Short-read data can be found at s3.climb.ac.uk/ vapor-benchmark-data/vapor_benchmarking_realdata_reads_filtered_ 18_03_18.tar, or hosted at the European Nucleotide Archive under project accession PRJEB33950

Summary

Introduction

Single-stranded, segmented negative-sense RNA viruses of the family Orthomyxoviridae. Influenza A and B have eight genome segments, with major antigenic recognition sites within the two proteins haemagglutinin (HA) and neuraminidase. Accumulation of point mutations within the antigenic recognition sites of HA and neuraminidase can result in host immune evasion, thereby causing annual seasonal epidemics (Petrova and Russell, 2018; Taubenberger and Kash, 2010). Influenza type A is a zoonotic virus infecting a wide range of avian and other non-human species (Sautto et al, 2018). These viruses have the capability to reassort leading to the emergence of new strains (Bouvier and Palese, 2008), which can result in pandemics

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