ViSeL: An interactive Virtual Laboratory for DNA Sequencing1
Robert Giegerich, Dieter Lorenz
Practical Informatics
University of Bielefeld
Box 100131
D-33501 Bielefeld
{robert|dieter}@techfak.uni-bielefeld.de
Phone: +49 521 106 2913|2956
Abstract
Multimedia technology, based on low-cost PC hard- and software, offers a chance to improve
traditional academic education as well as industrial training. As an interdisciplinary project
between the Department of Genetics and the Department of Computer Science, the
multimedia based CBT-Software ViSeL - Virtual Sequencing Laboratory - is currently under
development.
The aim of this project is to offer an integrated solution for improving laboratory education
through new media. The first use of ViSeL in higher education was in April 1997 in the
Department of Genetics. The main expectations concerning the field test of ViSeL are a vast
reduction of educational costs in an expensive field of laboratory training. Furthermore,
ViSeL can help to improve the quality of individual education, while at the same time
overcrowded laboratories and seminars are relieved. Of course, the ultimate, hands on
laboratory work cannot be substituted by virtual laboratory experience. However, better
student preparation can help to decrease the danger of serious work accidents. All in all,
computer based multimedia methods in laboratory education can reduce the demand on
resources in a humane, ecological and economic way.
Keywords in decreasing order of relevance:
Training Application, Microworld, Multimedia Development, Curriculum Design,
Preference for presentation format: Poster Only
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The ViSeL project is supported by “Universitätsverbund Multimedia”, Nordrhein-Westfalen.
ViSeL – An Interactive Virtual Laboratory for DNA Sequencing
ViSeL – An Interactive Course in DNA Sequencing
1. A ViSeL Overview
1.1. Motivation
Practical laboratory training for science students tends to be a bottleneck in academic
education. Lack of sufficient space and tutoring personnel is a common phenomenon with
respect to introductory courses. In advanced courses, the cost of equipment and materials puts
further limitations on the intensity of student training. In fields like molecular biology,
training comprises sophisticated experimental methods and devices. This brings along the
risks of damage, improper use of contagious materials, or waste of highly purified (and hence
expensive) reagents.
In 1995, the Bielefeld genetics group hosted a single DNA sequencing machine, to be used by
research projects, occasional sequencing service for other groups in the biology and chemistry
departments, and for the training of students who specialized in genetics. The student load
suddenly doubled, when the new curriculum “Naturwissenschaftliche Informatik'' began to
funnel its third-year bioinformatics students into the laboratory courses. The question arose,
what computer science could do to alleviate the situation. At that time it had become apparent
that within a few years, low-cost PC hardware would be capable to support a new kind of
interactive, multimedia based tutoring systems. Our proposal for a “Virtual Sequencing
Laboratory” [ME/SK/1995; ME/SK/GI/1995] achieved a multimedia award2 in late 1995,
which in turn enabled us to attract some funding and start the development of ViSeL. A first
prototype was operational in 1997, used and evaluated as a supplement to the regular
laboratory course. The status described in the present paper is the beta-release of ViSeL,
scheduled to go out for a field test in autumn 1998.
1.2 . Educational Targets
If we regard the human learning process in first instance as an active interaction with the
environment, simulation tools can serve as an effective means to transfer knowledge. With the
aid of these programs, the user receives information about the specific work flow of
operations to create certain laboratory products. Students get a real impression of daily
laboratory work by interacting with typical laboratory instruments. They learn about specific
safety aspects and the use and function of technical devices, instruments and reagents.
There are a number of efforts to produce virtual learning environments [CHEMLAB/1996,
GENTEC/1997]. Additional projects started recently, due to the universities trying to develop
high quality teaching software (http://www.uvm-nw.de/; http://www-is.informatik.unioldenburg.de/ag/mm.html).
ViSeL is designed to teach to novices the main working steps of the complete DNAsequencing procedure, or just to refresh existing experience. The main target group are
university students of biology, who just get started with the different methods of gene
manipulation and sequencing techniques. Furthermore, ViSeL may be useful for all
institutions where gene sequencing is practised (e.g. in medical research). Let us emphasize
that the aim of this software development is to offer an educational tool that accompanies the
laboratory courses, and not to replace them. To reach this aim the following learning targets
are declared in the project concept:


2
Physical and biochemical foundations for the complete sequencing process, with focus on
“The Sanger chain termination reaction”.
The complete sequence of operations to determine the sequence of bases of cellular DNA.
“Best Multimedia Software” in the Multimedia Transfer Competition, ASK, 1995
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ViSeL – An Interactive Virtual Laboratory for DNA Sequencing



The appearance and usage of typical laboratory objects.
The proper use and dosage of reagents and their (bio)chemical function.
The functionality and operation of the ALFexpress sequencer.
1.3. The Curricular Concept
According to the learning targets mentioned above the following figure illustrates the ViSeL
curricular.
Figure 1: Overview on the integral ViSeL concept
The tutorial section
Within the tutorial section the user acquires fundamental methodical, biochemical and
technical foundations required for the work in the virtual and real laboratory. This program
part can be compared to a hypertext book and is divided into four subchapters.
The multimedia glossary
The multimedia glossary can be accessed from any module at any point in time. It includes
multimedia entries declaring biochemical and biotechnological knowledge.
The virtual laboratory
The ViSeL simulation environment makes it possible to carry out the complex course of
DNA-sequencing in a realistic manner. Within this virtual scene students get an impression of
real laboratory work by interacting with typical laboratory objects. Moreover a series of video
clips visualize some work steps in real time.
Additional working material
The additional working material has a significant meaning because it supports traditional
mnemonics. It is a paper workbook including questions about the theoretical subject. Students
work with this material during the computer sessions and it might be helpful afterwards in real
laboratory work or for exam preparation.
“Real” laboratory work
To train skill expertise, students have to visit the real DNA sequencing lab and do the physical
handling with genuine entities.
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ViSeL – An Interactive Virtual Laboratory for DNA Sequencing
2. The ViSeL Tutoring Section
2.1. Contents of the Tutoring Section
Chapter 1: Introduction
In the first chapter the user gets an overview about the aim, the contents and structure of the
ViSeL-Software and its curriculum.
Chapter 2: The fundamentals of molecular genetics
This chapter describes basic biochemical and genetic knowledge. The different
macromolecules (DNA, RNA sorts, amino acids, proteins) are introduced and their special
functions are explained [LIN/1989]. Furthermore answers are given to the questions: What is
the genetic code and how is it connected with the synthesis of proteins? How does the
mechanism of DNA replication work? What are the important techniques applied in
biogenetic laboratories? What are the functions of plasmides and bacteriophages in the
context of DNA cloning? [HO/MO/1993/I; -/II; -/III; LOR/1996; W/G/W/Z/1993]
Beside these subjects a molecule viewer (RasMol) is introduced to encourage the students'
competence concerning biochemical data visualization. RasMol is a free of charge
visualization tool for non-commercial purpose developed at Glaxo Research & Development,
Greenford, UK [RAS/1995].
Chapter 3: Sequencing method according to Frederick Sanger
The main method used to sequence DNA today was developed by Frederick Sanger in 1980.
This method uses a DNA polymerase (usually the DNA polymerase from T7 phage or Taq
polymerase) to synthesize a new strand of DNA from the template whose sequence is to be
determined. This reaction is poisoned by the addition of a molecule that will cause the
reaction to terminate. To understand this reaction, we must recall the mechanism of
replication (explained in “The fundamentals of molecular genetics”), which is a polymerase
reaction that makes a new strand from deoxynucleotides (dNTPs - a combination of dATP,
dTTP, dGTP, and dCTP) and a template [HEN/1995; REC/1997].
Chapter 4: The ALFexpress Sequencer
The basic mode to operate the ALFexpress sequencing device is based on the Sanger
sequencing method mentioned above. This device consists of three main components:
The electrophoresis unit, the AM V3.0 software (which is responsible for the correct
controlling of the device), and diverse kits of chemicals.
The focus of this learning matter is to demonstrate the correct handling of the ALFexpress
system software and starting the ALFexpress sequencer run, including all work steps from
preparing the gel cassette, mounting the cassette into the sequencer, starting the run via AM
V3.0 software, to the computer analysis of the raw data material. Further important
information is given about hardware safety mechanisms and handling the dangerous chemical
kits [PHARM/1995].
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ViSeL – An Interactive Virtual Laboratory for DNA Sequencing
2.2. Global and Local Functions in the Tutorial Section
Figure 2: An example from the section „ On molecular foundation“
Global functions:
Kompaß-Button:
Menue-Button:
Lexikon-Button:
Vor-Button:
Zurück-Button:
This button branches off to the main overview page.
“
individual chapter overview page.
“
multimedia glossary.
“
next page.
“
previous page.
Local functions :
On every page there are different local functions available for the user. The most frequently
required local functions are the sensitive fields. By clicking on one of these yellow underlined
fields, the user activates particular textual, auditory and visual media. The media illustrate the
current learning subject. The red sensitive fields branch off to another page.
A further local function is the Tutor-Button. By clicking on this button, the user will activate a
video-audio lecture that illustrates the learning subject in form of an animation or a slide
show. The duration of the lecture is indicated by a corresponding notice on the button.
2.3. Particular Criteria for the Development of the Tutoring Section
Beside the known guidelines in software and CBT development theory [BAL/1996;
GA/ZÜ/1993; SCHUL/1996] and the rules of desktop and graphic design [MS/1995;
JE/PA/1992] the following criteria are of special interest for the realization of the ViSeL
tutorial part:





A spare and pure functionality and a non-ambiguous definition of interaction design.
A consistent design of the desktop throughout the different chapters.
Effective usage of various media types according their own characteristics.
Short system responses and a maximum of media quality.
Factual correctness of all subjects.
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ViSeL – An Interactive Virtual Laboratory for DNA Sequencing
3. The Virtual Laboratory Environment
3.1. Operating the Virtual Lab – The Procedure of DNA Sequencing
We enter the virtual lab via an overview page (Figure 3). It gives us an overview of the three
laboratory fields, organised according to the major steps in the overall sequencing procedure:
„Isolierung“ (DNA Isolation), „Aufbereitung“ (DNA Preparation) and „ALFexpress“
(ALFexpress DNA sequencing). A particular lab field is selected by mouse-click on one of
the tables. The novice student starts with the field „Isolierung“. Within this initial phase the
DNA is isolated from the cells and its quantity is estimated. The whole sequencing procedure
is divided into 14 subtasks distributed among the three main fields mentioned above. Each of
the particular subgoals contains up to 9 operation steps. All in all, there are about 100 steps to
be performed in the appropriate order.
Figure 3: Main overview page lab
We now enter the DNA isolation section. Figure 4 represents this working area.
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ViSeL – An Interactive Virtual Laboratory for DNA Sequencing
Figure 4: Working section – „Isolierung“
A mouse-click on the lab handbook (1) activates/deactivates a flow diagram on the grey board
(2) that describes the process of the current operation step. The user gains an insight view of
the entire work flow, by clicking on the yellow text fields on the board tables.
The graphic below shows the context of the current task within the whole DNA sequencing
procedure. All actions that must be carried out are appearing on the instruction board. The
current working area is about cracking the cell membrane and its nucleus.
Figure 5: Flow diagram - Instruction board
The user has now the possibility to start a video that will show the process of the current
operation steps in a real laboratory.
The actual handling of objects in the virtual laboratory is explained by an example:
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ViSeL – An Interactive Virtual Laboratory for DNA Sequencing
The first operation step
contains the disinfection of a
glass rod. Disinfection is
normally realised with a
Bunsen burner. When the user
moves the mouse pointer to
the glass rod, s/he will get a
textual information about the
state of the object.
For disinfecting the nonsterile glass rod, the user must
move the object „unsteriler
Glasstab“ onto the object
„Bunsenbrenner“ (drag) and
then has to release the mouse
button (drop).
The interaction interpreter
now checks, if the operation
step is allowed and
immediately gives a
corresponding positive
response to the user.
This drag & drop scheme is repeated successively throughout each task. The positive result is
announced by a tick on the instruction board.
The right mouse button:
By clicking on an object with the right mouse button, the user obtains important information
about appearance and use of the object. The following picture shows the composition of the
P1 solution.
Figure 6: Description of P1 solution
Navigation in the lab occurs with the aid of a navigation bar. This bar will be visible when the
mouse pointer is moved to the upper edge of the screen. The user moves through the different
learning sections by means of this bar.
Figure 7: Navigation bar
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ViSeL – An Interactive Virtual Laboratory for DNA Sequencing
3.2. Interaction in the Virtual Laboratory
In the initial design of a virtual environment, a wide variety of interaction mode appears to be
useful. However, the interaction model of a learning environment (in contrast to other
environments such as virtual reality games) should adhere to a parsimony principle. A small
number of interaction forms is quickly learned. This helps to focus the user's attention on the
subject matter rather than on the mechanics of the environment. This supports an explorative
learning style. Hence ViSeL supports a very simple and transparent model of interaction. First
of all, there are no dynamic processes going on: All ViSeL operations are direct results of user
interaction.
ViSeL distinguishes three kinds of interaction: navigation, explanation, and manipulation.
These are mapped on three modes of user input: "touch", "click", and "drag&drop" in the
following way: Navigation is achieved by clicking on specifically designed buttons, or n areas
of the lab which are to be visited.
Explanation is triggered in two ways: Moving the mouse cursor over an object lights up a
short notice about the object's nature and its current state (see above). Longer explanations
(video, animation, text) are triggered by button clicks. Navigation and explanation never
change the state of objects.
Object manipulation is restricted to interaction between two objects, and is mapped on the
"drag&drop" user action. The implementation of the concrete set of object interactions
roughly proceeds according to the following scheme:
I,
Name, describe and visualize all objects participating in the work process. Let n be the
number of Objects. For each object, determine a set of attributes which suffice to
model the object's behaviour.
II,
Give a verbal description of the complete sequence of events and number all
intermediate steps. Let k be the number of steps. Ensure that in each step at most two
objects interact. By si(Oj) we denote the state of Oj at time i, i.e. the set of attribute
values associated with object j after execution of step i.
III,
Declare the initial state vector S0 = [s0(O1),..., s0(On)].
IV,
Let Ol,Or be the objects interacting in step i. Define the transition function for step i as
acti (si-1(Ol), si-1(Or)) (si(Ol), si(Or))
V,
For each step i, define an output function that determines the audio-visual feedback to
the user, depending on the object states involved in step i.
VI,
Implement a Moore-Machine, based on the above-mentioned sets of states and
transitions.
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ViSeL – An Interactive Virtual Laboratory for DNA Sequencing
4. The Glossary - A Multimedia Database
Every CBT application should enable the user to access the learning matter via alternate
paths. The multimedia glossary is a way to access declarative knowledge through the use of
keywords. It consists of a register with terms, textual definitions and additional audio-visual
media. On the one hand, these components are embedded in the ViSeL tutorial section on the
other hand, they are available as raw files on the storage medium. The user has the possibility
to access all media assigned to a specific expression at once. Figure 9 shows the ViSeL
glossary query for the term "DNA":
Figure 8: The glossary viewer
As one can see the term “DNA" is explained by text including blue marked hotwords. By
clicking on a hotword the user gets its explanation (Nukleotid, Replikation). The two buttons
to the right of the text field browse the history of already displayed terms. Furthermore it is
indicated that there is one direct link into a chapter of the ViSeL tutorial part (Link: Structure
of DNA). The appearance of the two flags in the right, below the browsing buttons indicate,
that in addition there are videos and pictures to look at.
The different media are simply associated with these terms, consequently, no considerably
higher quantity of data is the result. The additional costs lie in the connection of these media,
i.e. knowledge administration. For that reason a database and a development interface was
implemented to reduce this administrative effort. On the developer’s side this device makes it
possible to name the expression, to give additionally a textual explanation, to embed audiovisual material and to generate/remove automatically all referring expressions (hotwords).
This program was developed for universal use and is not limited to the ViSeL program. The
following figure shows this interface:
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ViSeL – An Interactive Virtual Laboratory for DNA Sequencing
Figure 9: The database development interface
5. Prospect
A major lesson drawn from the ViSeL effort concerns the high amount of human labour
flowing into the design of high quality media and a consistently reacting virtual environment.
The high production cost of multimedia learning environments must currently be seen as a
major obstacle to their increased use, particularly in academic education. Hence we need
better tools to support the development of such environments.
Abstracted from the experiences collected with ViSeL, a generic learning laboratory will be
developed. This environment represents the raw form of a virtual biological laboratory. It
contains the basic learning units and a supply of laboratory devices. Furthermore the essential
laboratory interactions are implemented. In this way we hope to reduce the effort of
constructing specialised learning environments.
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ViSeL – An Interactive Virtual Laboratory for DNA Sequencing
6. Literature, Software, Media
[BAL/1996]
[CHEMLAB/1996]
[GA/ZÜ/1993]
[GENTEC/1997]
[HEN/1995]
[HO/MO/1993/I]
[HO/MO/1993/II]
[HO/MO/1993/III]
[JE/PA/1992]
[LIN/1989]
[LOR/1996]
[ME/SK/1995]
[ME/SK/GI/1995]
[MS/1995]
[PHARM/1995]
[RAS/1995]
[REC/1997]
[SCHUL/1996]
[W/G/W/Z/1993]
H. Balzert, Lehrbuch der Software-Technik: Software-Entwicklung,
Spektrum Akademischer Verlag, Heidelberg, 1996.
Corel Corporation, Corel-Chemlab ™, V1.00, CD-ROM, Ottawa,
1996.
E. Gabele, B. Zürn, Entwicklung Interaktiver Lernprogramme, Band 1:
Grundlagen und Leitfaden, Schäffer-Poeschel Verlag, Stuttgart,1993.
T. Kubli, P. Linder, C. Manzoni, Gentechnik – Interaktiv
experimentieren – Virtuell im Biozentrum, CD-ROM, OEKOSOPHIE©,
Basel, 1997.
W. Hennig (Hrsg.), Genetik, Springer Verlag, Berlin/Heidelberg, 1995.
(P. 205, 206)
T. Hoffman, M. Montag, Die Zelle 1, Aufbau der Zelle und Struktur von
DNA, RNA und Proteinen, Spektrum Videothek, Spektrum
Akademischer Verlag, Heidelberg, 1993.
T. Hoffman, M. Montag, Die Zelle 2, Grundlegende Zellprozesse:
Transkription - Translation - Replikation, Spektrum Videothek,
Spektrum Akademischer Verlag, Heidelberg, 1993.
T. Hoffman, M. Montag, 1993, Molekularbiologie: Einführung in die
Standard Techniken; Spektrum Videothek, Spektrum Akademischer
Verlag, Heidelberg, 1993.
Jenz & Partner, Grafische Bedienoberflächen – Ein Leitfaden für das
Anwenderdesign, Jenz&Partner GmbH, Erlensee, 1992
H. Linder (Hrsg.), Biologie: Lehrbuch für die Oberstufe, Schroedel
Schulbuchverlag, Hannover, 1989.
D. Lorenz, Entwicklung multimedialer Lernprogramme & Manipulation
von Objekten im virtuellen Labor, Diploma thesis, Bielefeld, 1996.
F. Maier, G. Skrock, Design interaktiver Lernprogramme auf Basis von
Multimedia, Diploma thesis, Bielefeld, 1995.
F. Maier, G. Skrock, R. Giegerich, Computer Based Training Software
– Ein interaktiver DNA-Sequenzierkurs, Report 95-02, Forschungsbericht der Technischen Fakultät, Abteilung Informationstechnik,
Bielefeld, 1995.
The Windows Interface Guidelines for Software Design, Microsoft
Press, Richmond, 1995.
Pharmacia Biotech AB, ALFexpress instruction manual - 56-1173-21
Edition AA, Uppsala, Sweden, 1995.
R. Sayle, RasWin Molecular Graphics V2.5, Glaxo Research &
Development, Greenford, Middlesex, UK, 1994.
(http://www.glaxowellcome.co.uk/software/rasmol/index.html)
A. Reckmeier, Die DNA Sequenzierung nach Sanger: Eine
multimediale Lernsoftware, Diploma thesis, Bielefeld, 1997.
R. Schulmeister, Grundlagen hypermedialer Lernsysteme: Theorie –
Didaktik-Design, Addison-Wesley, Bonn/Paris, 1996.
J. D. Watson ,M. Gilman ,J. Witkowski,M. Zoller, Rekombinierte DNA:
2. Auflage, Spektrum Akademischer Verlag, Heidelberg/Berlin/Oxford,
1993.
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