Abstract

BackgroundPreparedness for a possible global pandemic caused by viruses such as the highly pathogenic influenza A subtype H5N1 has become a global priority. In particular, it is critical to monitor the appearance of any new emerging subtypes. Comparative phyloinformatics can be used to monitor, analyze, and possibly predict the evolution of viruses. However, in order to utilize the full functionality of available analysis packages for large-scale phyloinformatics studies, a team of computer scientists, biostatisticians and virologists is needed – a requirement which cannot be fulfilled in many cases. Furthermore, the time complexities of many algorithms involved leads to prohibitive runtimes on sequential computer platforms. This has so far hindered the use of comparative phyloinformatics as a commonly applied tool in this area.ResultsIn this paper the graphical-oriented workflow design system called Quascade and its efficient usage for comparative phyloinformatics are presented. In particular, we focus on how this task can be effectively performed in a distributed computing environment. As a proof of concept, the designed workflows are used for the phylogenetic analysis of neuraminidase of H5N1 isolates (micro level) and influenza viruses (macro level). The results of this paper are hence twofold. Firstly, this paper demonstrates the usefulness of a graphical user interface system to design and execute complex distributed workflows for large-scale phyloinformatics studies of virus genes. Secondly, the analysis of neuraminidase on different levels of complexity provides valuable insights of this virus's tendency for geographical based clustering in the phylogenetic tree and also shows the importance of glycan sites in its molecular evolution.ConclusionThe current study demonstrates the efficiency and utility of workflow systems providing a biologist friendly approach to complex biological dataset analysis using high performance computing. In particular, the utility of the platform Quascade for deploying distributed and parallelized versions of a variety of computationally intensive phylogenetic algorithms has been shown. Secondly, the analysis of the utilized H5N1 neuraminidase datasets at macro and micro levels has clearly indicated a pattern of spatial clustering of the H5N1 viral isolates based on geographical distribution rather than temporal or host range based clustering.

Highlights

  • Preparedness for a possible global pandemic caused by viruses such as the highly pathogenic influenza A subtype H5N1 has become a global priority

  • This paper proposes a new approach to pandemic control by constantly monitoring molecular evolution at both macro level and micro level using comparative phyloinformatics

  • Global preparedness for H5N1 pandemic has been declared as the top priority of global health agencies such as CDC

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Summary

Introduction

Preparedness for a possible global pandemic caused by viruses such as the highly pathogenic influenza A subtype H5N1 has become a global priority. The time complexities of many algorithms involved leads to prohibitive runtimes on sequential computer platforms This has so far hindered the use of comparative phyloinformatics as a commonly applied tool in this area. The H5N1 virus is believed to have acquired the hemagglutinin (HA) gene from A/goose/Guangdong/1/96 H5N1 and A/teal/ Hong Kong/W312/97 H6N1, while the internal genes were received from A/quail/Hong Kong/G1/97 H2N2 or A/teal/Hong Kong/W312/97 H6N1, respectively [2], [3]. Even though this particular strain was eliminated by culling millions of chicken, its ancestors remains circulating in aquatic birds

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