The LIFEdb database in 2006
Alexander Mehrle*, Heiko Rosenfelder, Ingo Schupp, Coral del Val1, Dorit Arlt,
Florian Hahne, Stephanie Bechtel, Jeremy Simpson2, Oliver Hofmann3,
Winston Hide3, Karl-Heinz Glatting1, Wolfgang Huber4, Rainer Pepperkok2,
Annemarie Poustka and Stefan Wiemann
Division Molecular Genome Analysis and1Division Molecular Biophysics, German Cancer Research Center,
Im Neuenheimer Feld 580, D-69120 Heidelberg, Germany,2European Molecular Biology Laboratory, Cell Biology
and Biophysics Programme, Meyerhofstrasse 1, D-69117 Heidelberg, Germany,3South African National
Bioinformatics Institute, Old Chemistry Building, University of the Western Cape, Bellville 7535, South Africa and
4European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK
Received September 14, 2005; Revised October 19, 2005; Accepted October 27, 2005
LIFEdb (http://www.LIFEdb.de) integrates data from
large-scale functional genomics assays and manual
cDNA annotation with bioinformatics gene expres-
sion and protein analysis. New features of LIFEdb
include (i) an updated user interface with enhanced
querycapabilities,(ii) aconfigurable outputtable and
the option to download search results in XML, (iii) the
integration of data from cell-based screening assays
addressing the influence of protein-overexpression
on cell proliferation and (iv) the display of the relative
expression (‘Electronic Northern’) ofthe genes under
investigation using curated gene expression onto-
logy information. LIFEdb enables researchers to sys-
tematically select and
proteins of interest, and presents data and informa-
tion via its user-friendly web-based interface.
LIFEdb (1) has been implemented towards the integration,
mining and visualization of functional genomics data. The
system was designed to cope with large amounts of hetero-
geneous data originating from high-throughput experimental
approaches (2) and to relate these data with information
from an automatic bioinformatics analysis of the proteins
The LIFEdb web-interface provides integrated access to
cDNA-data, experimental results and bioinformatics informa-
tion via several search forms, enabling researchers to system-
atically select and characterize genes and proteins of interest.
By linking results to further external databases, the user is
empowered to view the functional information within a larger
context. Here we describe the newly added content in the
LIFEdb database and highlight recent developments of inter-
faces to query and visualize the data.
NEW LAYOUT AND ADDED FUNCTIONALITY
The user interface has been completely updated and revised
(Figure 1). Search fields are grouped into panels according to
functionality. Users may either use the simple search field with
a built-in analysis logic recognizing the type of input string or
use additional fields to search for biological identifiers or
experimental results. We have added a configurable search
page in which groups of search fields can be selected or
de-selected. The groups comprise experimental results,
predictions, cDNA/protein data and keyword fields. The cri-
teria of the respective groups can be connected by logical
operators (‘AND’, ‘OR’). This allows for a ‘fine tuning’ of
Users can customize the output by selecting the experi-
mental data or additional information to be displayed. The
latter comprises annotations (gene names, chromosomal posi-
tion of the cDNAs), identifiers (gene symbols, cDNA acces-
sion numbers, RefSeq/UniGene IDs) and bioinformatics
analysis data (predictions, protein motifs). By default, results
are shown in a tabular format but they can be downloaded as
XML as well, to allow further processing with spreadsheets,
databases or statistics software.
NEWLY ADDED DATA
LIFEdb was initially developed to publish data on full-length
cDNAs and the subcellular localization of the encoded
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Nucleic Acids Research, 2006, Vol. 34, Database issueD415–D418
proteins (4). During the past two years the content of the
database has constantly grown to currently contain data on
1500 cDNAs and localizations and microscopic images of
some 1000 proteins. We have now integrated a first dataset
from a cell-based screening assay that addresses the influence
of protein-overexpression on cell proliferation (5). This screen
comprised initially 103 proteins and is the first posting of such
high-throughput data in an open-access database (Figure 2).
Expression constructs encoding proteins of interest and fused
to green fluorescent protein derivates at either their N- or C-
terminus were transfected into mammalian cells, and effects of
protein-overexpression on G1/S-phase transition were meas-
ured. This was done using a high-content screening micro-
scope by monitoring the incorporation of BrdU through
immunofluorescent staining. The data were statistically ana-
lysed using a linear model correcting for systematic and ran-
dom errors. This resulted in a Z-score, based on a smoothed
local regression function for each single experiment. Proteins
with positive values of Z are considered to be an activator and
those having a negative value to be a repressor of cell prolif-
eration. The results for each investigated protein were calcu-
lated as the median value of the Z-scores of all replicate
experiments carried out with the respective ORF. To obtain
a measure of the significance (P-value), the set of Z-scores of
one protein was compared with the overall distribution of
Z-scores for all proteins via the two-sided Wilcoxon test. Res-
ults from the cellular screen can be searched for with a suitable
search field, where users can specify ifactivators, repressors or
off for the minimal accepted P-value. Results are displayed as
an extra column showing the median Z-score and the accom-
panying P-value. The distribution of the Z-scores for each
ORF can be viewed as a histogram in an extra window (see
Figure 2) that is accessible via a hyperlink. There, the data on
N-terminal fusion constructs (CFP–ORF) are displayedin dark
blue and values from C-terminal fusion constructs (ORF–
YFP) are displayed in green. The numbers of proteins with
attached information from functional profiling will continu-
ously increase as more proteins are screened.
In addition to these experimental results, we included data
on the relative tissue expression of the genes under investiga-
tion (‘Electronic Northern’, Figure 2). The calculation is based
on the number of ESTs for every gene that were sequenced
mostly in large scale projects (6–10). We used the UniGene
(11) EST-dataset and eVOC ontologies (12) which curate this
dataset in a detailed manner, to obtain a controlled tissue
vocabulary. dbEST library mappings to the ontologies were
obtained from the eVOC website (http://www.evocontology.
were used for the tissue-definitions (for a list, see http://www.
EST-libraries assigned to the respective term (or sub-term)
were pooled. cDNAs were mapped to UniGene cluster IDs
via the GenBank accession number in the UniGene dataset.
The relative gene expression of one transcript was calcu-
lated using the number of ESTs in the respective UniGene
cluster belonging to each ontology term which was then nor-
malized for each term (for details on the calculation see http://
The datasets, mappings and calculations are updated
when new versions of the respective datasets become
The expression for each gene is shown for the terms of the
anatomical system as colored boxes in the table output. Boxes
are labeled with an abbreviation of the underlying definition.
Relative gene expression values are indicated by different
search results can be downloaded in XML (right).
D416 Nucleic Acids Research, 2006, Vol. 34, Database issue
colors. Values <1 (relative ‘under-expression’) are displayed
in blue and values >1 are in red (relative ‘overexpression’).
Darker colors represent a higher degree of under- or overex-
pression. Boxes in white indicate that no UniGene expression
of the respective gene was identified in that particular group of
tissues. Information on the underlying numbers (ESTs in the
respective cluster and tissues) is displayed upon moving the
mouse over the boxes. This information is included in the
In the future, we will integrate results from further ongoing
cellular screens and extend the cDNA-annotation by integrat-
ing other external databases that cover for instance IPI iden-
tifiers and ontology terms.
This work was supported by National Genome Research
Network grants 01GR0101
Bundesministerium fu ¨r Bildung und Forschung (BMBF),
and in part by EU grant 503438 (TRANSFOG). Funding to
pay the Open Access publication charges for this article was
provided by the German Cancer Research Center (DKFZ).
and 01GR0420 bythe
Conflict of interest statement. None declared.
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Figure 2. Presentation of new data in LIFEdb. ‘Electronic Northern’ data are shown color-coded indicating the relative over-representation (red) or under-
shown in a separate column with an extra window ploting the Z-scores of the single experiments for each protein (right) and the statistical significance of the result
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