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Web Services and Interoperability in Genomics
4.4 ENCODE pipeline: applying Web Services
ENCODE (the Encyclopedia Of DNA Elements) was launched in September 2003 by
the National Human Genome Research Institute. The goal was to identify all functional
elements in the human genome sequence. In the pilot phase 1 percent (30 Mb) from
44 selected regions of the human genome has been analysed by ENCODE consortium
researchers (Birney et al., 2007).
GENCODE is a sub-project of ENCODE, which seeks to identify all protein-coding
genes in the ENCODE selected regions. For each protein coding gene this means the
delineation of a complete mRNA sequence for at least one splice isoform, and often for
a number of additional alternative splice forms. The contributions from the BioSapiens
partners are focused on information from a protein annotation perspective. Special attention
is given to the potential aspect of alternative splicing and the putative effect it has
on functional diversification of genes.
In the pilot phase of the Biosapiens project the properties of the coding sequences
for the 44 regions have been analyzed by the Biosapiens partners separately. The results
from single groups were collected and the main findings were published (Tress et al., 2007).
Furthermore the entire collection of annotations created by all partners was made available
as supplementary material for the publication.
In the current phase of the BioSapiens project the goal is establish a scale-up of the
annotation approach applied to the pilot ENCODE sequences to cover the 100% of the human
genome, including all the isoforms. For the scale-up, the ENCODE Pipeline (EPipe)
was constructed (this Biosapiens deliverable), which is a WWW service that allows researchers
to compare functional annotations for all splice variants of a given gene in an
automatic way, or alternatively use it for analysis of mutated sequence variants containing
SNPs. The author of this thesis. This author has been responsible for the development
of the main parts of the EPipe software as well as for implementing a large part of the
modules (feature predictors). The EPipe projects is an ongoing effort which has involved
a number of people during its development.
4.4.1 Collecting Web Services clients in EPipe
EPipe uses a number of local and remote resources for protein feature prediction. The
ability of EPipe to connect to remote resources via Web Services is incorporated within
the individual modules. This put a great deal of flexibility as to which resourses to support
(e.g. BioMoby, SOAP etc). The pipeline is shown in figure 4.3.
EPipe itself is offered both as a SOAP web service (http://www.cbs.dtu.dk/ws/
EPipe and a traditional web interfece (http://www.cbs.dtu.dk/services/EPipe). A
schematic overview of the workflow in EPipe is shown in figure 4.4.
4.4.2 Mapping Pfam annotations to protein structure: mecA
In Staphylococcus aureus the mecA gene encodes a penicillin-binding protein (PBP2a),
resulting in Methicillin resistance (Ender et al., 2009). The EPipe software can be used to
map a range of different relevant features onto the protein structure, in order to visualize
differences between homologs of this protein. In this example however, a single MecR1
protein from Staphylococcus aureus strain A5937, GenBank accession no. EEV85461, is
processed. Figure 4.5 shows the structure browser of EPipe which allows the user to
browse the different features that are predicted, by showing the mapping onto the protein
structure. Here, the three Pfam domains Transpeptidase, MecA N, and PBP dimer appear
as significant hits.
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