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MarFlow Sample Tracking
Werner Van Belle1* - werner@yellowcouch.org, werner.van.belle@gmail.com
1- Internet & Communication Technology
Norut IT; Research Park; 9294 Tromsø; Norway
Abstract
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Tracking samples throughout many different organisations which all use different labeling protocols and are located at different geographical locations is difficult. This R&D program aims at the creation of a sample tracking system. The system will offer a) a labelling protocol designed for storage and unique identification of samples integrating many different labeling techniques b) a decentralised storage capacity (every organisation can store the data locally) and c) a security model which will take into account the ethics of sample exchange. A second aspect of the project aims at offering integration and data exchange towards existing sample tracking systems and analysis programs. We believe that this project and associated effort will reduce the costs of future information systems as well as increase cooperation between different research groups. The longer term goal of this project is the development of one or more commercial products related to sample tracking in cooperation with interested partners.
Keywords:
peer to peer, distributed systems, ambient intelligence, ubiquoutous computing, pervasive actors
Reference:
Werner Van Belle; MarFlow Sample Tracking; Ideas in Bioinformatics; YellowCouch; November 2004
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In Norway, biobanks and high throughput experiments are driven by
advanced experimental techniques such as micro-arrays, mass
spectrometry,
HPLC, X Ray crystallography and others. These techniques can be used
to screen for specific activities, to develop detailed models of
biological
systems or to obtain detailed understanding of single samples. Such
experiments typically consist of a pipeline of different techniques,
in which samples are transferred between different stages. In every
stage a sample is analysed and then, depending on the outcome, routed
in the pipeline. Given the huge amount of samples transferred in these
pipelines, research groups struggle with sample tracking. Some users
(notable hospitals) make use of locally developed sample tracking
systems, some use off-the-shelf software without external inputs or
outputs, while others use pen and paper. Sometimes, other ingenious
techniques are appropriate such as RF identifaction and DNA markers,
which might be a much more natural way of identification.
In this context,
where integration of different labeling protocols
is necessary and where sample exchange between different research
groups require a decentralised approach, many laboratory information
management systems do not scale up.
In this project we
propose the creation of a system that will help
in tracking samples, thereby integrate existing sample tracking
techniques.
For groups currently in need of a sample tracking system, SampleTrack
will a) offer tracking using barcode labelling and b) offer a flexible
local storage peer to peer information system. For groups who already
make use of a sample tracking system, SampleTrack will a) integrate
with the existing system and b) integrate with the local labelling
protocol. A large emphasis will be placed on offering a flexible access
right system to guarantee privacy and honour ethics. E.g; sending
out local patient information should not be done, however it should
still be possible to track the sample over different organisations.
The requirements for a sample tracking systems that spans multiple
organisations are different from standard in-house sample tracking
systems. We have been in communication with a number of different
research groups. Among them are Marbank (the national marine biobank),
Marbio (the analysing laboratory associated with Marbank), the
molecular
genetics group at the University of Tromsø, Norstruct (the
Norwegian
structural biology centre), Labforum (the micro-array facility at
the University of Tromsø) and Probe (the proteomics unit at the
University
of Bergen). This lead to the identification of a number of requirements
for a sample tracking system. We describe them briefly below.
The first requirement of any sample tracking system is that all samples
can be uniquely identified. At any moment it should be possible to
look at a sample and retrieve the associated sample information.
Depending
on the research group the requirements are slightly different.
- R1.1: Sample Labelling: Some research
groups do not yet have
a suitable sample labelling protocol. For these research groups it
is necessary to offer a well designed standard.
- R1.2: High throughput: In order to be
viable in the near
future, the labelling protocol should be able to handle large
quantities
of samples. This means that it should be possible to quickly label
a lot of samples. This can be done by making use of barcode labelling
and by group labelling. E.g; instead of labelling every vial in a
rack, it is also possible to refer to a position in a uniquely labelled
rack.
- R1.3: Integration: Some research
groups already have a sample
labelling strategy. It should be possible to use these local labelling
protocols interwoven with the labelling protocol we will develop.
Especially our own expertise with DNA markers and RFC identification
will bring a new input into the aspects of laboratory information
management systems.
The system should be flexible to use. This means that the steps between
installing the software and actually using it should be as small as
possible.
- R2.1: Associated Information. Every
research group has its
own information it wants to associate with a sample. Some research
groups want to associate physical location with a sample, others want
to know to which project a certain sample belongs. It is difficult
to foresee what information is necessary, therefore, it is essential
that the system is extremely flexible in adding new information to
samples.
- R2.2: Process Information. Sometimes
samples are tracked
throughout a process. It should be possible to follow a sample within
a certain process, retrieve the sample history and so on.
- R2.3: User Interface. The system
should offer a number of
easy to use front ends and installers.
- R2.4: Sample Searching: The system
needs to offer a way to
search for specific samples, based on their associated
meta-information.
One of the key requirements that came forth by a number of research
groups is that a centralised sample tracking system would be highly
inappropriate. Most research groups want to have local control over
their own data.
- R3.1: Decentralised. The system
should be decentralised,
which means that all sample informations of local created samples
should be stored locally.
- R3.2: Distributed. Although all
sample information is stored
locally, it is still necessary that information can be shared between
multiple partners. For instance, when a sample is transferred from
one research group to another, the exchange of visible information
should be transparent.
- R3.3: Disconnected. In some
situations samples are handled
at remote locations, where there is no immediate connection towards
the sample tracking system. In such a disconnected setup, it is
necessary
that the system synchronises data transparently and smoothly.
- R3.4: Redundancy: To ensure that data
is not lost, it is
necessary to have some redundancy in the sample tracking system.
Currently in some companies, sample tracking is performed by using
all kinds of tools. In order for this project to succeed it is crucial
that SampleTrack will be able to integrate with other systems.
- R4.1: Import/Export: depending on the
system already in use
it might be necessary to import and export data in and out of the
system. E.g: export data to excel files or input data from excel files.
- R4.2: Synchronous Linking: when
possible it might be helpful
to create an immediate link towards already existing infrastructure.
- R4.3: Extensibility: the sample
tracking system we will develop
should be accessible by other programs as well. This will ensure that
research groups can alter and modify the system as they need.
Another big concern of the different research groups was that the
system should support ethics and allow to associate private information
with samples.
- R5.1: Security: Given the ethical
committee its decisions
about the visibility of patient information, it is necessary to ensure
that suitable security policies can be linked to the samples. E.g;
patient data should not be visible by anybody else beside the M.D.
himself.
- R5.2: Access Domains: Sometimes
access should be granted
towards anybody working within the research unit or within a specific
research project.
There exists many laboratory information systems, which are typically
very good at satisfying local requirements for one research lab,
however
they almost never succeed in allowing the exchange of samples (and
associated information) towards other systems and research groups.
Also, they fail to integrate more advanced techniques of sample
identification,
such as DNA markers. Furthermore, communication with vendors of
commercial
sample tracking systems has shown that information exchange is often
considered to be a bad business strategy. Commercial systems are closed,
have an expensive and
unnatural licensing and software
tailoring requires support from the original seller. Clearly such
a closed world strategy and extensive payments per license are
difficult
to integrate in a cooperative research environment.
This proposal aims
at bringing a usefull sample tracking system towards
many reasearch groups, whilst offering a natural integration between
them.
In this section we briefly cover some of the requirements we are
already
aware of with our partners
- Marbank: every sample in the marine
biobank will be associated
with multimedia (digital photos, video, literature),
geographic
information (date, geographic position,
field preparation,
notes, storage in transit, hazard), biological
information
(species, common name, weight, length, sex, age) and expert
annotations (determined by, reference
annotations). The preservation
of every sample, initial and available amount and location
in the freezer (freezer name, section, rack and box) will also
be
stored. Further useful information is tracking
which research
groups are actually using which sample. Another aspect of
Marbank
is that samples will be gathered off-shore,
which means that
when the floating lab comes back all data should propagate to the
appropriate locations.
- Marbio: Marbio will test for specific
sample activity by
making use of a pipeline. the typical process starts by extracting
the preserved sample into a water phase and an organic phase. In this
step a sample is transformed into multiple other samples using specific
preparation methods. These extracts are then routed through a HPLC
fractionation which will split the extracts into fractions. For every
fraction we need to keep track of the column,
eluation/gradient,
time/top, absorbans,
flow speed and storage
parameters. These different fractions will then be tested for
bioactivity
using different protocols. These can be tests on anti-tumor,
anti-inflammatory, anti-viral
and anti-bacterial
tests. The sample tracking systems should keep track of all these
samples and the processes that have been applied to them.
- Norstruct: The FUGE-technology
platform for structural biology
is carrying out structural analysis on biologically active
macromolecules,
both in connection with internal projects in the laboratory and for
external partners nation-wide that are using the services we provide.
The selected target for structural studies will be carried through
a ``pipeline'' including many steps; target selection, evaluation
and identification, sequencing, cloning, recombinant expression,
biochemical
and biophysical characterisation, structure determination,
crystallisation,
data collection and structure analysis. Each of the steps will, for
each target, create a range of data (of variety of formats) that needs
to be stored, both for documentation purposes and for subsequent
analyses
for optimisation of procedures. Since Norstruct is a national
laboratory
with obligations towards ``external customers'', clear and easy
access to data and documentation is required.
The sample
exchange between the above mentioned research groups happens
in a pipeline, going from the marbank, which gathers samples on sea,
stores them, towards marbio which analyzes them and selects samples
for further analysis through Norstruct, which in itself containes
an entrie internal pipeline.
Furthermore, there
are relations with the following partners:
- Probe: Probe is currently working
together with a Belgian
unit to develop their local sample tracking system. An immediate
integration
with their system will make sure that the software forms a bridge
between different research groups. At probe samples are analysed using
multiple different techniques. For instance for a Maldi TOF analysis
it is important to keep track of the digestion
procedure followed,
which digestive was used, what time, what buffering.
Afterwards it is necessary to keep track on which
spots the
sample was placed and what the output of the
machine was given
a certain laser strength, polarity and technician. Extra
useful information is to know from which lab
the sample came
and for which project.
- The Institute For Molecular Genetics:
(at the university
of Tromsø) currently looks for a solution to keep track of
plasmids
in a freezer. Information associated with every plasmid is the creator,
who has used it, how
much is left and how much was originally
present, the name of the plasmid
and the location in
the freezer.
- Fiskeriforskning: Norut IT has been
working together with
Fiskeriforskning for a couple of years already with respect to sample
tracking in the area of fish identification using RFC chains and DNA
markers, based on microsattelites and SNP's.
These projects
have been funded by Innovation Norge (through Mabit). Currenlty we
believe that the experience we got from there should certainly make
it possible to broaden our scope and involve more partners and start
developing a more integrated, scaleable and reusable software line.
Figure 1:
An overall view on the SampleTrack sample tracking
program.
![Image NorSaTrackProgram](./NorSaTrackProgram.png) |
The overall program we present contains three distinct elements. The
first element is the user community which drives the project by using
the software and communicating with us with respect to their needs.
The second element is the development of usable prototypes in order
to satisfy the needs of the different users and the last part is the
innovative part. The innovation of this project lies in the application
and refinement of techniques which are nowadays being developed in
the research community. The SampleTrack program will bring this
research
to an applied level by a) using research where applicable, b) making
research applicable where necessary and c) inventing new techniques
where none exists. A second innovation of this project lies in the
value it offers to the scientific community. The SampleTrack system
offers tool support for the scientific community to work together
in a better and easier way. This will especially become important
whenever research laboratories will transfer samples in high throughput
mode.
Figure 2:
Running time of the different work packages and tasks
![Image NorSaTrack](./NorSaTrack.png) |
The work program (covering the entire scientific program) consists
of 6 work packages, each divided in a number of tasks. Due to space
constraints we keep the description as small as possible. The total
project contains 56 MM spanning 2 years.
This work package is concerned with
- T1.1 [1MM]: gather overview of existing labelling protocols in
the
different groups
- T1.2 [1MM]: designing and identification model, which integrates
multiple protocols as one
- T1.3 [3MM]: develop internal meta-data representation of samples
and processes, which is secure and allows to adding extra information
- T1.4 [3MM]: develop program and API to store and access data
- T1.5 [3MM]: deploy barcode printer, scanner and driver software
- T2.1 [6MM]: develop lab interconnection protocol which will
connect
different local databases to each other
- T2.2 [3MM]: develop propagation protocol throughout the peer to
peer network, which introduces redundancy
- T2.3 [3MM]: develop synchronisation protocol after reconnection
- T3.1 [2MM]: develop security model, using multi-user key-rings
and
so on, avoiding user identification
- T3.2 [2MM]: develop identification domains
- T4.1 [9MM]: develop linker programs toward existing databases
&
tools
- T4.2 [1MM]: develop API useable by other programs, including a
web
back-end
- T5.1 [3MM]: develop installer
- T5.2 [3MM]: develop application front-end
- T5.3 [3MM]: develop web front-end
- T6.1 [1MM]: do requirement analysis
- T6.2 [2MM]: SampleTrack website covering program, documentation
and so on
- T6.3 [2MM]: Presentations and seminars about SampleTrack
- T6.4 [10%]: Administration and project management
The program consists of two major milestones. M1:
The first
milestone (at the end of the first half year), is the deployment of
a local information tracking system at multiple locations. This early
milestone will give us feedback throughout the remainder of the project
and will allow us to refine the information tracking system further.
M2: The second milestone is the opening of
the information
tracking system towards different organisations. This milestone is
located in the middle of the second year. The last milestone refers
to the dissemination of the results obtained in this high visibility
project.
Despite the practical nature of this project, there are a number of
aspects which are strongly rooted in current day research. Below we
briefly touch upon them.
- Regression Analysis: In order to be able to guarantee that any
new
version of the software is compatible with old versions (backward
compatibility) we will investigate the use of Petri-nets as a
tool
to do automatic regression testing. Also, the applicability of
Petri-nets
should make it possible to verify whether any future versions will
still have possibilities to offer new behaviour (forward
compatibility).
- Correct Interface Usages: If software is developed to link with
existing
tools and data formats, it is crucial to be sure that the format is
exactly as it is supposed to be. To guarantee this we will use formal
interface and data descriptions which can be checked vigorously. Also,
this should make it possible to verify that external programs
interfacing
with the SampleTrack sample tracking system behave properly.
- Secure peer to peer information exchange. The exchange of
information
in peer to peer networks is nowadays used to transfer (often illegal)
data between partners. The decentralised nature of peer to peer
networks
makes them very robust but at the same time very difficult to handle.
How this can be done properly is still one of the areas of
investigation.
Especially the subproblems of identification of users and samples
as well as the honouring of security requirements is still a research
challenge.
- Automatic data synchronisation. Peer to peer networks rely upon
some
form of automatic data synchronisation. This field, which is closely
related to concurrent systems, requires solutions for every specific
problem at hand. In this specific case of sample tracking it is
necessary
to have some information exchange which follows the actual physical
exchange of samples. Nevertheless at the moments when multiple data
fields exists, it is necessary to have some intelligent synchronisation
mechanism.
- The development of a security model is highly dependent on how
users
think about their data. There is little knowledge on how biological
and ethical sensitive information propagates throughout human networks
and where information naturally stops. Knowing this information is
crucial to develop a highly suitable security model. Such a model
should allow us to develop a trust propagation model. In the context
of secure peer to peer networks, Norut IT has requested for funding
at Forskningsrådet to investigate the possibilities of creating a
scalable and secure peer to peer network. This project is called
TRUSTNET.
The longer term
goal of this project is the development of one or
more commercial products related to sample tracking in cooperation
with interested partners. Our past and ongoing relations with
Fiskeriforskning
about sample tracking, should certainly make it possible now to broaden
our scope and involve more partners to make the software more
integrated,
scaleable and reusable.