title: Comparative phyloinformatics of virus genes at micro and macro levels in a distributed computing environment.
abstract: BACKGROUND
  Preparedness 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.
  
  
  RESULTS
  In 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.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Genvea Biosciences, 53 Craig Road, #04-01, Singapore 089691. dtsingh@genvea.com
authors.forename: Dadabhai T
authors.initials: DT
authors.lastname: Singh
authors.forename: Rahul
authors.initials: R
authors.lastname: Trehan
authors.forename: Bertil
authors.initials: B
authors.lastname: Schmidt
authors.forename: Timo
authors.initials: T
authors.lastname: Bretschneider
mesh_terms: D019295:Computational Biology / Q000379:methods*; D003195:Computer Communication Networks; D003205:Computing Methodologies; D004252:DNA Mutational Analysis / Q000379:methods*; D019143:Evolution, Molecular; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics*; D009439:Neuraminidase / Q000235:genetics*; D010802:Phylogeny; D014764:Viral Proteins / Q000235:genetics*
chemical_list: D014764:Viral Proteins; D009439:Neuraminidase