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Towards standardized experiments production and
experiment management for
heterogeneous array platforms Stefan Wölfl, Peter
Slickers, Steffen Kube Clondiag Chip
Technologies, Jena, Germany, http//www.clondiag.c
om Klinik für Innere Medizin, Friedrich-Schiller-U
niversität Jena, stefan_at_imb-jena.de
Abstract
Work flow

The aim is to collect the minimum necessary
information (MIAME) from experiments run under
the same conditions delivering reproducible
results. The main steps of the microarray life
cycle are covered by tools and intuitive
interfaces, which provide the database with all
relevant information. Our system supports
heterogeneous array platforms, process automation
and MIAME compliance. Important considerations
for the information management system
representation of the microarray production
process control and representation of the
hybridization process and distinction between
facility and user of the micro array
technology. See the website of the system
http//www.clondiag.com/products/sw/partisan
Gaining comparable experiment results is one
aspect of the current work in the microarray
community. The variety of parameters for
microarray experiments asks for an optimal
description of the complete microarray life cycle
(see also MIAME). Following steps identify this
life cycle production management (description of
the microarray), sample description, the
experiment itself with hybridization, image
acquisition, image analysis and data mining. The
tasks for which CLONDIAG is developing new
microarray technologies require a management
system which is open for new technologies (e.g.
new detection systems, protein/antibody arrays)
and ready to streamline the processes in a
microarray facility.
1. Scientific question (suitable for gene
expression studies) 2. Then the following
experimental steps Design of
experiment Array and experimental
plan Production of Arrays (or suitable of the
shelf arrays) Experiment Visualization of the
results (conversion in numerical
values) Analysis of the results Repeat and
compare (experimental work cycle) 3.
Comparison with other (gene expression)
experiments
Gene expression experiments can be clearly
divided in discrete steps
Partisan arrayLIMS solution

Analysis and comparison with other experiments
require a clear documentation of all experimental
steps Open structure of the LIMS databank
ensures Import and Export of experimental
data, accessory information and
results Adjustment to new specifications
The partisan arrayLIMS is build around the
requirements needed for the precise documentation
of array experiments. It allows the proper
development of any type of array experiment from
the initial scientific or diagnostic question to
the complete management of the whole laboratory
process. Starting at the design of the
scientific experiment all information to build
the array and to carry out the experiments can be
collected in substance feature tables. These are
combined with all sample features, the protocol
information, the raw experimental results (images
or others) and the results after analysis.
Import and setup of key information for
experiments Management of the data and
experiments (Lab Journal) Export of results for
presentation and use with other tools
All this can be summarized in four essential
tasks
Import
Management
Description of array
Import from heterogeneous platforms
Template and real objects One important feature
of the system is the differentiation between
templates and real objects. This concerns the
objects "bioarray", "protocol" and "substance".
Templates can be used as blue prints for real
objects or as objects "ready to use" (like
protocols). Real objects contain
inherited information from the template, but also
their own characteristics. Substance libraries
The annotation of substances allows the use of
predefined classes ( genes, oligonucleotides, PCR
fragments, tissues etc. ) with specific
attributes (sequences, accession numbers,
modifications etc). Comprehensive hierarchies and
networks can be built. The local administrator is
able to define new local classes and
attributes. Search and sort functions The
program contains a powerful database query
builder (hierarchical, class dependent). A
special focus of the search is to keep track with
the lifecycle of a work object. Example
question When was a specific design of a
microarray realized in real microarrays and for
which experiments were these microarrays
used. Multiuser environment PARTISAN is
designed as a multi-user-application. Multiple
users are able to login and work in the database
in parallel. Data can be easily shared and
exchanged within teams. Thus, all partners can
access all relevant information which is crucial
for optimized data analysis and supervision of
experimental quality. Also consistency of the
data of each user is guaranteed.
The combination of user defined substance import
and user defined array layout import allows the
management of various commercial arrays
(Clontech, Affymetrics etc.) or lab spotted
arrays. For arrays without geometry information
(e.g. Clontech), the system generates the
appropriate layout GAL definition. For a 3x2
block array a 6 line plus 5 line header text file
is defined. With the appropriate layout and probe
definitions imaging can be done with 5 mouse
clicks using the imaging tool IconoClust. In
addition, the system supports open ontologies,
which allows to manage all new classes of
substances, i.e. PCR fragements, image clones,
tissues or proteins.
Description of features
Gene expression results
Lab Journal
Export and Analysis
Production tracking system and electronic lab
journal for microarrays
For analysis experiments can be summarized in
result tables and graphically displayed
From array production, documentation of all lab
information on the experiments all important data
can be maintained and documented in the
system. This features are combined with data
analysis, which ensures that all data can be
traced back to their origin and to specific
experimental conditions. The project navigator
works like a file explorer or file manager. The
project navigator displays a specific project
which contains all relevant objects documenting
the experiments, the samples and all other
information. The single object sheet provides
information and functionality for a specific work
object or other single data sets. One can switch
between edit mode (edit properties of the object)
and view mode (compact view). The primary global
functions for a single object are search
where the object is used, access the
information, browse linked objects, delete
objects and copy objects to clipboard.
Visualization of experimental results using in a
scatter plot
Exchange of data (e.g. result tables) with other
database systems and specialized analytical
tools.
Open interface to connect from the database to
data mining tools required for the detailed
statistical analysis of array results.
Calibration standard
Standardized experimental conditions
Facilitate handling to ensure comparable
experimental conditions
Quantitative comparison between experiments
CLONDIAG's AP system is a single reactor assay
system combining DNA array analysis with
microfluidics and molecular reactions. The AP
system was developed to conduct sample
preparation, target amplification and labeling,
analysis of the target on the array and
interpretation of raw data within a single
system.
An other critical point to obtain high quality
experimental data for large scale array
experiments is the uniformity of experimental
conditions. Two approaches can be taken to
obtain this. One is to use a complex fully
integrated system that includes careful
monitoring of each experimental step.
Alternative, the experimental set up should be
compatible with the established work flow in the
laboratory. Experimental tools for both
strategies were developed at Clondiag.
Variation in imaging and measuring conditions is
a critical point in generating comparable
datasets for gene expression analysis. The
imaging process thus should be controlled using
an external calibration standard to ensure
comparable measurements.
CLONDIAGs FluorIS (made of fluorescent
polymers) provides an extrenal standard for
instrument and process optimization and
standardization for array experiments.
CLONDIAG's Array Tube AT is a revolutionary new
platform for performing easy and inexpensive
experiments with microarrays. The direct
implementation of high quality DNA arrays into a
standard micro-reaction tube allows to carry out
all hybridization and analysis procedures without
highly specialized equipment .
Clondiag CT Jena and Friedrich-Schiller-University
Jena are partners of the Jene Center for
BioInformatics supported by the Geman Minsitry of
Science and Technology (BMBF)