Experimental Visual Environment
The EVE Project
Bercovici Sivan
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Experimental Visual Environment
Table of content
Table of content ............................................................................................................. 2
Introduction .................................................................................................................... 3
Goal ............................................................................................................................ 3
Tool Overview ........................................................................................................... 5
Requirements ................................................................................................................. 8
Design ............................................................................................................................ 9
Information ................................................................................................................ 9
Information Provider ................................................................................................ 10
Information Consumer ............................................................................................. 10
Tool .......................................................................................................................... 10
Tool Input................................................................................................................. 11
Tool Output .............................................................................................................. 11
Tool Category .......................................................................................................... 11
Toolbox .................................................................................................................... 11
Workspace................................................................................................................ 11
Implementation ............................................................................................................ 12
Input ......................................................................................................................... 12
Manual nucleotide sequence input ....................................................................... 12
Nucleotide sequence file input ............................................................................. 13
Range annotation file input .................................................................................. 13
Fasta loader .......................................................................................................... 13
Sequence tools ......................................................................................................... 14
Add range annotation ........................................................................................... 14
Filter range annotations........................................................................................ 14
Search repeats ...................................................................................................... 15
Break sequence by selection ................................................................................ 15
Pair alignment ...................................................................................................... 16
Sequence viewer ...................................................................................................... 17
Statistics ................................................................................................................... 18
Sequence pattern histogram ................................................................................. 18
Histogram viewer ................................................................................................. 18
Position specific nucleotide frequencies .............................................................. 19
Position specific frequencies viewer .................................................................... 19
Blast ......................................................................................................................... 21
Blast two groups .................................................................................................. 21
Blast results viewer .............................................................................................. 21
Extending EVE ............................................................................................................ 23
Encapsulating the Data ............................................................................................ 23
Creating the Tool ..................................................................................................... 24
Registering the Tool ................................................................................................. 26
Future directions .......................................................................................................... 27
Conclusion ................................................................................................................... 28
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Introduction
Over the past 30 years, the field of bioinformatics has shown an increasing
growth in research and development. Nonetheless, as we examine the academically
available research tools and infrastructures, we identify two major shortcomings:
-
There is no standard infrastructure/information format for
bioinformatics tools.
Many bioinformatics tools are hard to handle by biology researchers.
the
It is evident that no single environment exists in the academic world that offers an
integrated research tool. The same goes for bioinformatics information-handling
infrastructure. The result of the first shortcoming is that many times, the same
infrastructure is written over and over again, by different researchers. While there are
some libraries available (e.g., perl libraries that handle sequences), there is no
emphasis that newly added infrastructure will be able to communicate with legacy
infrastructure, and visa versa.
More and more environments are becoming available daily, each offering a set of
tools, supporting a set of formats, and producing new information sets in new formats.
This yields a constant learning stage by researches, as well as the lack of tools
interaction.
As many tools do not offer a visual interface, working with these tools is sometimes
hard, up to a point where the tool is not used by researchers although it offers
important information.
Goal
The main goal of EVE is to provide with a freely available, easy-to-use visual
working environment for the bioinformatics researchers, as well as an address for the
collection of bioinformatics tools developed in different locations.
The EVE project attempts to deal with the two shortcomings described in the previous
section by offering bridges between different information formats, and providing a
convenient visual tools’ pipe-line construction environment.
We believe that by encapsulating existing tools, and offering conversion services
between the formats these tools use, we could reach greater flexibility in the
construction of information pipe-lines. EVE does not constitute a new format,
suggesting it as a standard, but rather offers conversion services between different
formats. This allows different tools to be able to communicate. Thus, as long as new
tools will use the same sub-set of formats, EVE will be able to overcome the toolsinteraction problem.
We also believe that by emphasizing the visualization of the tools, we enable biology
researchers to actually use the tools in an intuitive fashion, shortening the learning
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curve, and increasing productivity. More importantly, with visualization in mind,
previously cryptic outputs from different tools are now more convenient to work with.
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Tool Overview
In EVE, a user interacts with a single workspace. Information processing
pipelines are drawn by the user as a graph, where the nodes are information
processing units, and edges mark the information flow between the different tools.
Figure 1 – the workspace
A set of tools in different categories is offered to the user in a browsing tree, at the left
side of the environment.
Figure 2 – the toolbox
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A user can drag a selected tool from the toolbox into the workspace. To build an edge,
representing information flow, a user has to click-and-drag a tool’s output (depicted
as blue circles in figure 1) into a tool’s input (depicted as red-circles in figure 1).
Each tool may have unique execution parameters. Double-clicking on a tool in the
workspace will enable a user to modify the tool’s specific parameters, prior to its
execution.
A tool is either valid or non-valid. In order to make a tool valid, one has to execute it.
A user is able to execute the entire graph by pressing on the play button at the top
tool-bar. When a tool is non-valid, it is marked with a red circle holding the letter ‘V’
inside (signifying a validity problem).
Figure 3 – Validity and Connectivity problems
Each tool either provides information, or consumes information provided by other
tools. Thus, a tool is either properly connected to its information providing tools, or
not. As one can study from the previous figure, if a tool’s connection is not satisfied,
the tool is marked with a red circle holding the letter ‘C’ in it (signifying connectivity
problem).
Sometimes, a tool will require the user to set its execution parameters. If a tool’s
parameters are not properly set, it would be indicated as a red-circle holding a ‘P’
letter in it (signifying parameters problem). This is shown in the next figure.
Figure 4 – Parameters problem
The environment offers two more state indication components. One is the logger
which logs events from the different tools and user interactions. The logger is
available in the lower part of the environment. The other component is the short
messages bar which displays context-sensitive messages, bellow the logger.
Figure 5 – The logger
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A user can drag tools across the workspace, re-arranging the graph layout. Also, a
user is able to remove tools and edges by first selecting them (with a mouse click),
and pressing the delete button.
To learn about the different tools, a user can read the available tool-tips by pointing
with the mouse on a tool, in either the workspace or the toolbox browsing tree.
Pointing on a tool’s inputs or outputs will reveal the type of information consumed or
produced by the tool, respectively.
Figure 6 – Tool-tips
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Requirements
After identifying the shortcomings of current tools, we define the following
requirements from the EVE tool:

Ease of use
The tool should be usable in an intuitive fashion.
An emphasis should be made making to tool as visual as possible.

Short learning curve Learning how to use the tool should inflict a
marginal learning curve.

Flexibility
The tool should allow the interaction of different
tools from the field of bioinformatics.

Basic inputs support The tool should support basic data formats for
the elementary data used by most bioinformatics applications.

Basic data-structures The tool should provide data-structure for the
elementary data types handled by most bioinformatics tools.

Basic viewers
The tool should provide with a set of basic
viewers for the examination of the basic data-structures.

Extendibility
The tool should be easily extendable to support
new arising external bioinformatics tools.

Free
The tool should be available freely.
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Design
In this section, we review the fundamental building blocks of EVE. The most
basic component is the information objects. These objects are either produced by
tools, consumed by tools, or both. When information is produced by the tool, it is
pushed to the information providers objects, which lie inside a specific tool output. A
tool may have, of course, several outputs. From the other side of the information flow
arrow, a tool may have several tool inputs. Each tool input may have several
information consumers. The tool retrieves the information it requires for processing
from the information consumers.
This flexible design allows us to easily develop new tools with different number of
inputs and outputs that uses the supported information types, while offering a
different processing service.
Information
As stated above, the most basic component in eve is the Information class, which
encapsulates the basic data-units on which processing is made.
The Information interface defines the basic methods that must be provided by any
object that wishes to be able to move through a pipeline defined under the EVE
environment.
In EVE, we have implemented several Information objects that were marked as
fundamental to bioinformatics research.
Among the implemented basic-data units of Information are:
1. Nucleotide Sequence
Holds a single nucleotide sequence, as well as
specially marked sub-ranges. Other information stored in these objects is
the sequence name, and a multi-line comment.
2. Multiple nucleotide sequence
Holds a set of nucleotide sequences
3. Histogram
Holds statistical information. The x-axis represents the
different categories, and the y-axis represents the value measured for each
category.
4. Motif
Holds multiple-sequences as well as position-specific
nucleotide frequencies.
5. Blast two groups information
the given multiple-sequences.
Holds the pair-wise alignment results of
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Information Provider
An Information Provider interacts with a corresponding set of information consumers
(i.e., Information Consumer objects). It can interact with a ranging number of
information consumers, as defined during construction, sending them a copy of the
required internally stored information upon request.
Information Consumer
An Information Consumer interacts with a corresponding set of information providers
(i.e., Information Provider objects). It can interact with a ranging number of
information providers, as defined during construction. The consumer can ask from
any of the registered providers for a copy of the information they hold.
Tool
This is one of the most basic components of EVE - the skeleton of a tool from which
all EVE tools must inherit. It provides the mechanism for setting up the tool's input
and output, and defines the interface for tool processing, and description.
The processing of a tool is divided into 5 stages:

Pre-process It defines the part of the tool’s execution that must occur prior
to the tool’s main processing stage. This stage may be executed any time
during pipe-line execution, as long as this time is before the tool’s main
execution stage.

Acquire information At this stage, the tool retrieves all information from the
tools on which it depends for input. This stage may take place any time before
the actual processing stage, yet after the input sources have all finished
executing and the pre-processing stage of the tool has finished.

Processing
The main processing stage of the tool. At this stage all data
needed for processing is available for the tool to use. The processing stage
takes place after the information acquiring stage has finished.

Post information
This stage, which takes place after the main tool’s
processing stage has finished, is responsible for pushing the information
through the tool’s output. This stage is important so that the tools which
depend on the output of this tool, will be able to retrieve the required data.

Post-process
This stage may execute any time after the information
posting stage has finished. It is intended mostly for cleanup.
Breaking the tool’s execution into these 5 steps, enables better task scheduling, as
well as enforces programmers to give the required attention to all of the tool’s natural
execution stages.
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Tool Input
A tool input consumes information from different information providers,
based on the information consumers that it holds. A Tool may have several tool input
objects attached to it.
Tool Output
A tool output provides information for different information consumers, based
on the information providers that it holds. A Tool may have several tool output
objects attached to it.
Tool Category
A Tool Category object is used to manage a set of tools inside the toolbox.
Toolbox
A singleton class is that manages the set of tools in EVE. The toolbox acts as a
container of tools, set inside different containing categories.
Workspace
The workspace, implemented in the GraphPanel class, provides the main EVE
workspace. Upon this component, the information pipeline will be drawn in the shape
of a flow graph.
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Implementation
In this section, we review the tools, models and viewer, implemented in this version
of EVE.
Input
EVE provides a few basic input methods, either manually or from file. In the
next sub-sections, we describe these methods (i.e., EVE tools).
Manual nucleotide sequence input
Description: This tool can be used by EVE users to manually enter a nucleotide
sequence.
Inputs: None.
Outputs: Supports both SingleNucleotideSequence and MultipleNucleotideSequence
output.
Parameters: The parameters of this tool are the sequence name, the actual sequence,
and a comment to the sequence. The parameter editing panel is depicted in the next
figure.
Nucleotide sequence manual input
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Nucleotide sequence file input
Description: This tool is used to load a plain nucleotide sequence from a file
Inputs: None.
Outputs: Supports both SingleNucleotideSequence and MultipleNucleotideSequence
output.
Parameters: Double-clicking on this tool will open the default file browser, allowing
the user the select the file that is to be loaded.
Range annotation file input
Description: This tool is used to load range annotations for sequences. The file format
is: <Range start position> <Range end position> <Range annotation string>.
Inputs: None.
Outputs: Range annotations information object.
Parameters: Double-clicking on this tool will open the default file browser, allowing
the user the select the file containing the range annotations that is to be loaded.
Fasta loader
Description: This tool is used to load multiple nucleotide sequence from files in the
FASTA format.
Inputs: None.
Outputs: The tool outputs MultipleNucleotideSequences information.
Parameters: Double-clicking on this tool will open the default file browser, allowing
the user the select the file that is to be loaded.
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Sequence tools
In this section we describe the basic sequence tool provided in this version of
EVE. The tools are used to perform elementary tasks on the sequences.
Add range annotation
Description: This tool is used to annotated a given sequence with a given range
annotation.
Inputs: The left input is the single nucleotide sequence information, and the right
input is used to bring the range annotation to be used.
Outputs: This tool outputs both
MultipleNucleotideSequences objects.
a
SingleNucleotideSequence
and
a
Parameters: None.
Filter range annotations
Description: This tool is used to pre-select specific ranges in multiple nucleotide
sequence, for later processing.
Inputs: MultipleNucleotideSequence.
Outputs: MultipleNucleotideSequence.
Parameters: Users can not edit the parameters of this tool in the usual manner, but
rather during the execution of the pipe-line, a sequence range-browser will popup,
showing the available annotations for all of the input multiple nucleotide sequences.
The browser enables the user to select the desirable ranges.
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Search repeats
Description: This tool is used to search small patterns repeats provided by the user in
the input multiple nucleotide sequences. The results will be shown as annotated
ranges in the output MultipleNucleotideSequences object.
Inputs: MultipleNucleotideSequences.
Outputs: MultipleNucleotideSequences.
Parameters: A user has to insert the searched nucleotide pattern, as well as the
searched repeat number.
Search repeats in a given nucleotide sequences
Break sequence by selection
Description: This tool is used to break given nucleotide sequence into new multiple
nucleotide sequence according to the selection (i.e., annotated ranges).
Inputs: SingleNucleotideSequence.
Outputs: MultipleNucleotideSequences.
Parameters: None.
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Pair alignment
Description: This tool is used to perform either local or global alignment on two
given nucleotide sequences.
Inputs: The tool takes two inputs, each with a SingleNucleotideSequence information
object.
Outputs: MultipleNucleotideSequence.
Parameters: A user may input the alignment method (i.e., either global or local), as
well as the penalty matrix. This is depicted in the following figure.
Pair alignment parameters
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Sequence viewer
Description: The sequence viewer is one of the most important tools available in the
current version of EVE. It provides the users with a way to examine multiple
nucleotide sequences, and their annotated ranges.
The Sequence Viewer
As depicted in the previous figure, the viewer is constructed from 3 parts. The upper
quick navigation bar enables the user to set the viewing window size and location, and
gives a quick overview of the sequences and their annotated ranges. Change in the
sliding window will be reflected in the center viewing piece. The center viewing piece
shows the actual sequences, marking annotated ranges with a red color.
On the left side of the viewer, one can examine the annotated ranges of each sequence
separately. A user is also able to mark the ranges it wishes to examine. Checking to
range boxes will switch their visibility state on and off. These changes will be
reflected both in the quick navigation bar and the center nucleotide sequence viewing
piece.
Inputs: MultipleNucleotideSequences.
Outputs: None.
Parameters: A user can not edit the parameters of this tool. Double-clicking on the
tool when its state is valid will reveal the multiple nucleotide sequences viewer, and
enable the user to examine the input multiple nucleotide sequences.
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Statistics
The current version of EVE provides with two sequence-related statistics tool.
One focus on the short pattern statistics and the other tool focuses on position-specific
nucleotide frequencies.
Sequence pattern histogram
Description: This tool is used to examine patterns in certain length in the given
sequences.
Inputs: MultipleNucleotideSequences.
Outputs: HistogramInformation
Parameters: As depicted in the following figure, a user can set the size of the patterns
on which this statistical tool will gather information.
Sequence patterns - statistical tool parameters
Histogram viewer
Description: This tool is a general histogram viewer. It is not specialized to any
specific tool, but rather works with the generic HistogramInformation input.
Inputs: HistogramInformation
Outputs: None.
Parameters: There are no special parameters a user can set in this viewer, yet when a
user double-clicks on the tool when the tool is valid, the histogram viewer will appear.
The histogram viewer shows the statistical information given as input as an
histogram. As shown in the following figure, when a user points on a specific bar, a
tool-tip will appear reflecting the statistical information represented by the bar.
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The histogram viewer
Position specific nucleotide frequencies
Description: This tool is used to examine the position-specific nucleotide frequencies.
This tool is mainly used for the quick discovery of motifs, and consensus patterns in
multiple nucleotide sequence alignments.
Inputs: MultipleNucleotideSequence
Outputs: MotifInformation
Parameters: None.
Position specific frequencies viewer
Description: Visually similar to the sequence viewer tool, this viewer provides the
user with the ability to examine the position specific frequencies information gathered
by the position-specific nucleotide frequencies tool. The main change from the
previously described sequence viewer is that the center piece no longer presents the
sequences themselves, but rather the frequencies gathered.
Inputs: MotifInformation
Outputs: None.
Parameters: This tool does not take user parameters. When a user double-clicks on a
valid tool, the viewer will appear. The following figure shows the position specific
frequencies viewer.
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Position specific frequencies viewer
One can notice in the example above that there is a short 3-base consensus in the
beginning of the given 6 sequences.
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Blast
We support simple blast services, as an example of how external tools can be
easily encapsulated for use under the EVE environment.
Blast two groups
Description: This tool takes two groups of nucleotide sequences, and performs
alignment on all the pairs which are a combination of a nucleotide sequence from the
first group, and a nucleotide sequence from the second group. The tool that performs
the actual alignment is the blastn tool, which is executed locally.
Inputs: Two MultipleNucleotideSequences information objects.
Outputs: BlastTwoGroupsInformation
Parameters: A user can set the maximal allowed e-value. Any alignment which
produces an e-value above the user specified limit will disregarded.
Blasting Two groups - parameters
Blast results viewer
Description: This tool takes the blast results of the Blast two groups tools, and
enables the users to view them.
Inputs: BlastTwoGroupsInformation
Outputs: None.
Parameters: There are no unique parameters to be set by the user. When a user
double-clicks on a valid blast results viewer tool, the viewer will appear, showing the
given input results.
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Example for the blast viewer results
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Extending EVE
In this section we provide a step-by-step guide for the implementation of a
new tool. The motivation is to show how easy it is to extend the EVE tool,
encouraging the addition of new tools for the environment.
Encapsulating the Data
The first step in the construction of a new tool is to examine the type of
information it uses, as well as the type of data it produces. A programmer should first
examine the currently available Information objects, as the most basic types of data,
used by most bioinformatics applications, have been already implemented. We
encourage the re-use of these Information objects, so as to increase the interconnectivity with both currently available tools, and future implemented tools.
In case none of the Information object fit the requirements of the new tool (either for
input or output), a new class should written, implementing the light Information
interface. The most important point there is that a programmer should implement the
createCopy method which should create an entirely independent copy (i.e., deep
copy) of the Information object.
As an example, we provide the code for the single nucleotide information class.
public class NucleotideSequenceInformation implements Information {
public NucleotideSequenceInformation( NucleotideSequence seq ) {
this.sequence = seq;
}
public Information createCopy() {
return new NucleotideSequenceInformation(
new NucleotideSequence( sequence ) );
}
public String getDescription() {
return "Nucleotide sequence";
}
public Class getType() {
return NucleotideSequence.class;
}
public NucleotideSequence getSequence() {
return sequence;
}
private NucleotideSequence sequence;
}
The second step is to implement the Information Consumer and the Information
Provider interfaces for the newly created Information type. When implementing these
interfaces, one should notice two important points. The first point is that the
constructor of both the Information Consumer and the Information Provider must call
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the parent construction, providing the minimum and maximum number of information
clients as parameters. A zero in the maximum providers field will enable the user to
connect an infinite number of information providers to the specific information
consumer. These parameters will be enforced in the workspace, allowing a user to
connect only the allowed amount of edges between the tools.
The second important point is that the type method must be overriding so that it would
reflect the exact data type of the handled Information.
As an example, we provide the code for the nucleotide sequence information
consumer and provider:
public class SingleNucleotideSequenceInformationConsumer extends
InformationConsumer {
public SingleNucleotideSequenceInformationConsumer() {
super(1,1);
}
public NucleotideSequence getSequence() {
return
((NucleotideSequenceInformation)getInformation(0)).getSequence();
}
public Class type() {
return NucleotideSequenceInformation.class;
}
public String getDescription() {
return "Single nucleotide sequence information consumer";
}
}
public class SingleNucleotideSequenceInformationProvider extends
InformationProvider {
public SingleNucleotideSequenceInformationProvider() {
super(0,0);
}
public Class type() {
return NucleotideSequenceInformation.class;
}
public void setSequence( NucleotideSequence seq ) {
setInformation( new NucleotideSequenceInformation(seq) );
}
public String getDescription() {
return "Nucleotide sequence information provider";
}
}
Creating the Tool
When constructing a new tool, one should extend the Tool class. In order to
change the default image of the tool, it is recommended that during the construction
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of the tool (i.e., in the constructor), a new tool image would be loaded into the
toolImage variable.
Next, the programmer should initialize the tool’s inputs and outputs in the constructor
of the tool. The required number of inputs and outputs should be built from the
corresponding ToolInput and ToolOutput objects. These objects can hold numerous
information consumers and providers (consumers for inputs, and providers for
outputs). Upon constructing the inputs and outputs, they should be added to the tool
(during construction) using the addToolInput and addToolOutput methods.
As an example for the coding of a tool, we show the code for the nucleotide-patternhistogram tool constructor:
public SequenceHistogramTool() {
toolImage = new ImageIcon(getClass()
.getClassLoader()
.getResource("images/SequenceStatisticsToolIcon.gif"));
//
// Setup tool input/output
ToolOutput toolOutput = new ToolOutput( this );
toolOutput.addInformationProvider(
new HistogramInformationProvider());
addToolOutput( toolOutput );
//
// Two single nucleotide sequence inputs
ToolInput toolInput = new ToolInput( this );
toolInput.addInformationConsumer( new
MultipleNucleotideSequenceInformationConsumer() );
addToolInput( toolInput );
//
// Setup tool status
setParametersStatus( true );
invalidate();
}
It is important to notice that the programmer should implement the newInstance
method, returning a new instance of the new tool.
A user should implement four out of the five tool processing steps, by overriding the
following methods:




preProcess
process
postProcess
updateInformationProviders
The step in which the information is brought to the tool’s information consumers is
inherited from the Tool abstract class. Nonetheless, in most cases, a user would prefer
bringing the information a step forward from the different information consumers and
into the actual tool. It is recommended that this stage will be implemented as part of
the process method.
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In order to allow a user to interact with the tool, so as to set its specific parameters, a
programmer should override the editParameters method. This method will be invoked
when a user double-clicks a tool on the workspace.
Registering the Tool
The last step in the introduction of a new tool into EVE is the registration
stage. In order to register a tool into EVE, a programmer should add it to a category.
In case the tool belongs to a new category, this category must be constructed in the
EVEFrame class, during construction. Next, the tool should be added to the correct
category, following by the registration of the category with to the toolbox.
As an example, we provide the code for the registration of the statistics tools. This
piece of code is taken from the EVEFrame constructor:
category = new ToolCategory("Statistics");
category.addTool( new SequenceHistogramTool() );
category.addTool( new HistogramViewerTool() );
category.addTool( new GatherPositionSpecificFrequenciesTool() );
category.addTool( new PositionSpecificFrequenciesViewer() );
toolbox.addToolCategory( category );
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Future directions
EVE is in a preliminary stage. In order to enable users to actually work with
the tool, more external tools should be encapsulated. Among these tools are the
blastp, clustalW, ATR hunter, motif searchers, and more.
Interacting with tools available on the web is also an important step so as to increase
the richness of EVE. Internet available data-bases should be accessible through EVE
as well, thus providing the biology researcher with a single working center.
More file formats should be supports, apart from the plain sequence format, and the
FASTA format.
EVE is currently nucleotide-oriented, thus extending it to support amino-acids
sequences is also an important step.
The information viewers, such as the sequence viewer and position specific nucleotide
frequencies viewer should be more stable, allowing the examination of a large number
of long sequences. The viewers should also be extended, adding more visual
information such as an outline of the degree of consensus between the input
sequences.
More statistical tools should be implemented, providing the user the ability to locally
analyze and examine the data.
Persistency support is an important feature that will enable a user to save and load
workspaces. Some work should still be made on the improvement of the workspace –
the graph layout, and a non-bounded workspace.
A scripting interface should be added to allow advance users to interact with EVE and
its produced data through short scripts.
Another interesting direction would be to examine the possibility of scheduling the
independent tasks in a pipeline to different distant computers. This way a pipe-line
can be executed in a greater speed.
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Conclusion
EVE is an initial effort to provide a freely available, visual working
environment for the bioinformatics researchers. As shown in the previous sections,
EVE is easy to extend with both new tools and encapsulated external tools. EVE
provides with basic means for input, and viewing of data. The basic Information
objects provided by this version of EVE allow the flexibility of the tool, enabling
different tools to interact.
We conclude that the EVE tool marks the path we believe should be taken toward the
future working environment of bioinformatics researcher. As the number of tools
grow and the information they provides becomes more dense, researchers need a
convenient integrated environment which will enable them to interact with these tools
in an easy and non-cryptic manner.
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