Computational tools and Interoperability in Comparative ... - CBS

Abstract
The scientific community is witnessing an explosion in both the number and the complexity
of DNA sequencing projects. As sequencing equipment becomes more reliable,
faster and less expensive, new possibilities of applying the technology are opening up.
The early genome sequencing projects, dating back almost 15 years, presented only individual
microbial strains and the large efforts and scientific achievements at this time
qualified publication in high ranking journals. Today however, projects like the Human
Microbiome Project (HMP), Human Gut Microbiome Initiative (HGMI) and the Genomic
Encyclopedia of Bacteria and Archaea (GEBA) takes sequencing into a new era, to study
the genomes and ecological niches of entire populations consisting of thousands of microorganisms.
These initiatives put a demand for new analysis tools to process and derive
knowledge from the wealth of genomic information.
This thesis describes development of new tools and methods to study these types
of data. When the genome of characterized strains and environmental samples are sequenced,
the ribosomal RNA genes are commonly chosen as a starting point to describe
the phylogeny and diversity. The rRNA genes are often interpreted as an ‘evolutionary
chronometer’ and the RNAmmer software was developed as a tool to quickly and
consistently identify the rRNA genes allowing for large-scale analysis of phylogeny of complex
data sets. RNAmmer solved previous issues of the gene boundary accuracy, that
is observed when using BLAST approaches to mapping rRNA genes. The possibility to
accurately map the start of rRNA transcripts has allowed the investigation of promotor
structures of these highly expressed operons and a promotor analysis in E. coli K12 is
demonstrated by applying a mathematical model of the energetics involved in DNA helix
opening.
But a single gene, such as the 16S rRNA, can in nature not describe the phenotype
nor the full coding potential of an organism. This thesis describes the development of
the BLASTatlas tool, which is a visualization tool to overview similarity and differences
between any number of genomes, metagenomic samples or sequence databases from the
viewpoint of a reference genome. This software has proved to be a powerful tool to study
the localization and gain/loss of gene clusters, such as pathogenicity islands in virulent
organisms. The tool has been used in several research projects and collaborations and
was described as a cover article in Molecular BioSystems in 2008, and highlighted in the
journal Chemical Biology. Despite the usefulness of this tool, it became obvious that a web
based version, more “biologist friendly” with zooming capability, was needed. This lead
to the GeneWiz browser, which was developed in a joint effort with the IT staff at CBS.
The tool enables the user to interactively zoom from a global chromosomal scale down
the nucletide, while maintaining the overview of all data being presented in the plot. It
features disproportional zooming as known from google maps. At the time of writing this
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