Tempel: time-series mutation prediction of influenza A viruses via attention-based recurrent neural networks

2020 ◽  
Vol 36 (9) ◽  
pp. 2697-2704 ◽  
Author(s):  
Rui Yin ◽  
Emil Luusua ◽  
Jan Dabrowski ◽  
Yu Zhang ◽  
Chee Keong Kwoh

Abstract Motivation Influenza viruses are persistently threatening public health, causing annual epidemics and sporadic pandemics. The evolution of influenza viruses remains to be the main obstacle in the effectiveness of antiviral treatments due to rapid mutations. The goal of this work is to predict whether mutations are likely to occur in the next flu season using historical glycoprotein hemagglutinin sequence data. One of the major challenges is to model the temporality and dimensionality of sequential influenza strains and to interpret the prediction results. Results In this article, we propose an efficient and robust time-series mutation prediction model (Tempel) for the mutation prediction of influenza A viruses. We first construct the sequential training samples with splittings and embeddings. By employing recurrent neural networks with attention mechanisms, Tempel is capable of considering the historical residue information. Attention mechanisms are being increasingly used to improve the performance of mutation prediction by selectively focusing on the parts of the residues. A framework is established based on Tempel that enables us to predict the mutations at any specific residue site. Experimental results on three influenza datasets show that Tempel can significantly enhance the predictive performance compared with widely used approaches and provide novel insights into the dynamics of viral mutation and evolution. Availability and implementation The datasets, source code and supplementary documents are available at: https://drive.google.com/drive/folders/15WULR5__6k47iRotRPl3H7ghi3RpeNXH. Supplementary information Supplementary data are available at Bioinformatics online.

2020 ◽  
Vol 18 (01) ◽  
pp. 2040002 ◽  
Author(s):  
Rui Yin ◽  
Yu Zhang ◽  
Xinrui Zhou ◽  
Chee Keong Kwoh

Influenza viruses are persistently threatening public health, causing annual epidemics and sporadic pandemics due to rapid viral evolution. Vaccines are used to prevent influenza infections but the composition of the influenza vaccines have to be updated regularly to ensure its efficacy. Computational tools and analyses have become increasingly important in guiding the process of vaccine selection. By constructing time-series training samples with splittings and embeddings, we develop a computational method for predicting suitable strains as the recommendation of the influenza vaccines using recurrent neural networks (RNNs). The Encoder-decoder architecture of RNN model enables us to perform sequence-to-sequence prediction. We employ this model to predict the prevalent sequence of the H3N2 viruses sampled from 2006 to 2017. The identity between our predicted sequence and recommended vaccines is greater than 98% and the [Formula: see text] indicates their antigenic similarity. The multi-step vaccine prediction further demonstrates the robustness of our method which achieves comparable results in contrast to single step prediction. The results show significant matches of the recommended vaccine strains to the circulating strains. We believe it would facilitate the process of vaccine selection and surveillance of seasonal influenza epidemics.


eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Colin A Russell ◽  
Peter M Kasson ◽  
Ruben O Donis ◽  
Steven Riley ◽  
John Dunbar ◽  
...  

Assessing the pandemic risk posed by specific non-human influenza A viruses is an important goal in public health research. As influenza virus genome sequencing becomes cheaper, faster, and more readily available, the ability to predict pandemic potential from sequence data could transform pandemic influenza risk assessment capabilities. However, the complexities of the relationships between virus genotype and phenotype make such predictions extremely difficult. The integration of experimental work, computational tool development, and analysis of evolutionary pathways, together with refinements to influenza surveillance, has the potential to transform our ability to assess the risks posed to humans by non-human influenza viruses and lead to improved pandemic preparedness and response.


2020 ◽  
Vol 36 (10) ◽  
pp. 3251-3253 ◽  
Author(s):  
Congyu Lu ◽  
Zena Cai ◽  
Yuanqiang Zou ◽  
Zheng Zhang ◽  
Wenjun Chen ◽  
...  

Abstract Motivation Newly emerging influenza viruses keep challenging global public health. To evaluate the potential risk of the viruses, it is critical to rapidly determine the phenotypes of the viruses, including the antigenicity, host, virulence and drug resistance. Results Here, we built FluPhenotype, a one-stop platform to rapidly determinate the phenotypes of the influenza A viruses. The input of FluPhenotype is the complete or partial genomic/protein sequences of the influenza A viruses. The output presents five types of information about the viruses: (i) sequence annotation including the gene and protein names as well as the open reading frames, (ii) potential hosts and human-adaptation-associated amino acid markers, (iii) antigenic and genetic relationships with the vaccine strains of different HA subtypes, (iv) mammalian virulence-related amino acid markers and (v) drug resistance-related amino acid markers. FluPhenotype will be a useful bioinformatic tool for surveillance and early warnings of the newly emerging influenza A viruses. Availability and implementation It is publicly available from: http://www.computationalbiology.cn : 18888/IVEW. Supplementary information Supplementary data are available at Bioinformatics online.


2020 ◽  
Author(s):  
John T. McCrone ◽  
Robert J. Woods ◽  
Arnold S. Monto ◽  
Emily T. Martin ◽  
Adam S. Lauring

AbstractThe global evolutionary dynamics of influenza viruses ultimately derive from processes that take place within and between infected individuals. Recent work suggests that within-host populations are dynamic, but an in vivo estimate of mutation rate and population size in naturally infected individuals remains elusive. Here we model the within-host dynamics of influenza A viruses using high depth of coverage sequence data from 200 acute infections in an outpatient, community setting. Using a Wright-Fisher model, we estimate a within-host effective population size of 32-72 and an in vivo mutation rate of 3.4×10−6 per nucleotide per generation.


Author(s):  
Rui Yin ◽  
Zihan Luo ◽  
Pei Zhuang ◽  
Zhuoyi Lin ◽  
Chee Keong Kwoh

Abstract Motivation Influenza viruses are persistently threatening public health, causing annual epidemics and sporadic pandemics. The evolution of influenza viruses remains to be the main obstacle in the effectiveness of antiviral treatments due to rapid mutations. Previous work has been investigated to reveal the determinants of virulence of the influenza A virus. To further facilitate flu surveillance, explicit detection of influenza virulence is crucial to protect public health from potential future pandemics. Results In this article, we propose a weighted ensemble convolutional neural network (CNN) for the virulence prediction of influenza A viruses named VirPreNet that uses all eight segments. Firstly, mouse lethal dose 50 is exerted to label the virulence of infections into two classes, namely avirulent and virulent. A numerical representation of amino acids named ProtVec is applied to the eight-segments in a distributed manner to encode the biological sequences. After splittings and embeddings of influenza strains, the ensemble CNN is constructed as the base model on the influenza dataset of each segment, which serves as the VirPreNet’s main part. Followed by a linear layer, the initial predictive outcomes are integrated and assigned with different weights for the final prediction. The experimental results on the collected influenza dataset indicate that VirPreNet achieves state-of-the-art performance combining ProtVec with our proposed architecture. It outperforms baseline methods on the independent testing data. Moreover, our proposed model reveals the importance of PB2 and HA segments on the virulence prediction. We believe that our model may provide new insights into the investigation of influenza virulence. Availability and implementation Codes and data to generate the VirPreNet are publicly available at https://github.com/Rayin-saber/VirPreNet. Supplementary information Supplementary data are available at Bioinformatics online.


2017 ◽  
Author(s):  
Thorsten R. Klingen ◽  
Susanne Reimering ◽  
Jens Loers ◽  
Kyra Mooren ◽  
Frank Klawonn ◽  
...  

AbstractMonitoring changes in influenza A virus genomes is crucial to understand its rapid evolution and adaptation to changing conditions e.g. establishment within novel host species. Selective sweeps represent a rapid mode of adaptation and are typically observed in human influenza A viruses. We describe Sweep Dynamics (SD) plots, a computational method combining phylogenetic algorithms with statistical techniques to characterize the molecular adaptation of rapidly evolving viruses from longitudinal sequence data. To our knowledge, it is the first method that identifies selective sweeps, the time periods in which these occurred and associated changes providing a selective advantage to the virus. We studied the past genome-wide adaptation of the 2009 pandemic H1N1 influenza A (pH1N1) and seasonal H3N2 influenza A (sH3N2) viruses. The pH1N1 influenza virus showed simultaneous amino acid changes in various proteins, particularly in seasons of high pH1N1 activity. Partially, these changes resulted in functional alterations facilitating sustained human-to-human transmission. In the evolution of sH3N2 influenza viruses, we detected changes characterizing vaccine strains, which were occasionally revealed in selective sweeps one season prior to the WHO recommendation. Taken together, SD plots allow monitoring and characterizing the adaptive evolution of influenza A viruses by identifying selective sweeps and their associated signatures.


2021 ◽  
Vol 441 ◽  
pp. 161-178
Author(s):  
Philip B. Weerakody ◽  
Kok Wai Wong ◽  
Guanjin Wang ◽  
Wendell Ela

Author(s):  
Emily S. Bailey ◽  
Xinye Wang ◽  
Mai-juan Ma ◽  
Guo-lin Wang ◽  
Gregory C. Gray

AbstractInfluenza viruses are an important cause of disease in both humans and animals, and their detection and characterization can take weeks. In this study, we sought to compare classical virology techniques with a new rapid microarray method for the detection and characterization of a very diverse, panel of animal, environmental, and human clinical or field specimens that were molecularly positive for influenza A alone (n = 111), influenza B alone (n = 3), both viruses (n = 13), or influenza negative (n = 2) viruses. All influenza virus positive samples in this study were first subtyped by traditional laboratory methods, and later evaluated using the FluChip-8G Insight Assay (InDevR Inc. Boulder, CO) in laboratories at Duke University (USA) or at Duke Kunshan University (China). The FluChip-8G Insight multiplexed assay agreed with classical virologic techniques 59 (54.1%) of 109 influenza A-positive, 3 (100%) of the 3 influenza B-positive, 0 (0%) of 10 both influenza A- and B-positive samples, 75% of 24 environmental samples including those positive for H1, H3, H7, H9, N1, and N9 strains, and 80% of 22 avian influenza samples. It had difficulty with avian N6 types and swine H3 and N2 influenza specimens. The FluChip-8G Insight assay performed well with most human, environmental, and animal samples, but had some difficulty with samples containing multiple viral strains and with specific animal influenza strains. As classical virology methods are often iterative and can take weeks, the FluChip-8G Insight Assay rapid results (time range 8 to 12 h) offers considerable time savings. As the FluChip-8G analysis algorithm is expected to improve over time with addition of new subtypes and sample matrices, the FluChip-8G Insight Assay has considerable promise for rapid characterization of novel influenza viruses affecting humans or animals.


2021 ◽  
Vol 48 (4) ◽  
pp. 37-40
Author(s):  
Nikolas Wehner ◽  
Michael Seufert ◽  
Joshua Schuler ◽  
Sarah Wassermann ◽  
Pedro Casas ◽  
...  

This paper addresses the problem of Quality of Experience (QoE) monitoring for web browsing. In particular, the inference of common Web QoE metrics such as Speed Index (SI) is investigated. Based on a large dataset collected with open web-measurement platforms on different device-types, a unique feature set is designed and used to estimate the RUMSI - an efficient approximation to SI, with machinelearning based regression and classification approaches. Results indicate that it is possible to estimate the RUMSI accurately, and that in particular, recurrent neural networks are highly suitable for the task, as they capture the network dynamics more precisely.


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