Biomedical subjects

Karl-Heinz Glatting

Publications and source records attributed to Karl-Heinz Glatting.

10 recordsLinked to original sources

PubMed2006

CAFTAN: a tool for fast mapping, and quality assessment of cDNAs.

BACKGROUND: The German cDNA Consortium has been cloning full length cDNAs and continued with their exploitation in protein localization experiments and cellular assays. However, the efficient use of large cDNA resources requires the development of strategies that are capable of a speedy selection of truly useful cDNAs from biological and experimental noise. To this end we have developed a new high-throughput analysis tool, CAFTAN, which simplifies these efforts and thus fills the gap between large-scale cDNA collections and their systematic annotation and application in functional genomics. RESULTS: CAFTAN is built around the mapping of cDNAs to the genome assembly, and the subsequent analysis of their genomic context. It uses sequence features like the presence and type of PolyA signals, inner and flanking repeats, the GC-content, splice site types, etc. All these features are evaluated in individual tests and classify cDNAs according to their sequence quality and likelihood to have been generated from fully processed mRNAs. Additionally, CAFTAN compares the coordinates of mapped cDNAs with the genomic coordinates of reference sets from public available resources (e.g., VEGA, ENSEMBL). This provides detailed information about overlapping exons and the structural classification of cDNAs with respect to the reference set of splice variants. The evaluation of CAFTAN showed that is able to correctly classify more than 85% of 5950 selected "known protein-coding" VEGA cDNAs as high quality multi- or single-exon. It identified as good 80.6 % of the single exon cDNAs and 85 % of the multiple exon cDNAs. The program is written in Perl and in a modular way, allowing the adoption of this strategy to other tasks like EST-annotation, or to extend it by adding new classification rules and new organism databases as they become available. We think that it is a very useful program for the annotation and research of unfinished genomes. CONCLUSION: CAFTAN is a high-throughput sequence analysis tool, which performs a fast and reliable quality prediction of cDNAs. Several thousands of cDNAs can be analyzed in a short time, giving the curator/scientist a first quick overview about the quality and the already existing annotation of a set of cDNAs. It supports the rejection of low quality cDNAs and helps in the selection of likely novel splice variants, and/or completely novel transcripts for new experiments.

Chromosome Mapping↗

PubMed2006

GOPET: a tool for automated predictions of Gene Ontology terms.

BACKGROUND: Vast progress in sequencing projects has called for annotation on a large scale. A Number of methods have been developed to address this challenging task. These methods, however, either apply to specific subsets, or their predictions are not formalised, or they do not provide precise confidence values for their predictions. DESCRIPTION: We recently established a learning system for automated annotation, trained with a broad variety of different organisms to predict the standardised annotation terms from Gene Ontology (GO). Now, this method has been made available to the public via our web-service GOPET (Gene Ontology term Prediction and Evaluation Tool). It supplies annotation for sequences of any organism. For each predicted term an appropriate confidence value is provided. The basic method had been developed for predicting molecular function GO-terms. It is now expanded to predict biological process terms. This web service is available via http://genius.embnet.dkfz-heidelberg.de/menu/biounit/open-husar CONCLUSION: Our web service gives experimental researchers as well as the bioinformatics community a valuable sequence annotation device. Additionally, GOPET also provides less significant annotation data which may serve as an extended discovery platform for the user.

Artificial Intelligence↗

PubMed2006

The LIFEdb database in 2006.

LIFEdb (http://www.LIFEdb.de) integrates data from large-scale functional genomics assays and manual cDNA annotation with bioinformatics gene expression and protein analysis. New features of LIFEdb include (i) an updated user interface with enhanced query capabilities, (ii) a configurable output table 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') of the genes under investigation using curated gene expression ontology information. LIFEdb enables researchers to systematically select and characterize genes and proteins of interest, and presents data and information via its user-friendly web-based interface.

Cell Proliferation↗

PubMed2004

Applying Support Vector Machines for Gene Ontology based gene function prediction.

BACKGROUND: The current progress in sequencing projects calls for rapid, reliable and accurate function assignments of gene products. A variety of methods has been designed to annotate sequences on a large scale. However, these methods can either only be applied for specific subsets, or their results are not formalised, or they do not provide precise confidence estimates for their predictions. RESULTS: We have developed a large-scale annotation system that tackles all of these shortcomings. In our approach, annotation was provided through Gene Ontology terms by applying multiple Support Vector Machines (SVM) for the classification of correct and false predictions. The general performance of the system was benchmarked with a large dataset. An organism-wise cross-validation was performed to define confidence estimates, resulting in an average precision of 80% for 74% of all test sequences. The validation results show that the prediction performance was organism-independent and could reproduce the annotation of other automated systems as well as high-quality manual annotations. We applied our trained classification system to Xenopus laevis sequences, yielding functional annotation for more than half of the known expressed genome. Compared to the currently available annotation, we provided more than twice the number of contigs with good quality annotation, and additionally we assigned a confidence value to each predicted GO term. CONCLUSIONS: We present a complete automated annotation system that overcomes many of the usual problems by applying a controlled vocabulary of Gene Ontology and an established classification method on large and well-described sequence data sets. In a case study, the function for Xenopus laevis contig sequences was predicted and the results are publicly available at ftp://genome.dkfz-heidelberg.de/pub/agd/gene_association.agd_Xenopus.

Animals↗

PubMed2004

High-throughput protein analysis integrating bioinformatics and experimental assays.

The wealth of transcript information that has been made publicly available in recent years requires the development of high-throughput functional genomics and proteomics approaches for its analysis. Such approaches need suitable data integration procedures and a high level of automation in order to gain maximum benefit from the results generated. We have designed an automatic pipeline to analyse annotated open reading frames (ORFs) stemming from full-length cDNAs produced mainly by the German cDNA Consortium. The ORFs are cloned into expression vectors for use in large-scale assays such as the determination of subcellular protein localization or kinase reaction specificity. Additionally, all identified ORFs undergo exhaustive bioinformatic analysis such as similarity searches, protein domain architecture determination and prediction of physicochemical characteristics and secondary structure, using a wide variety of bioinformatic methods in combination with the most up-to-date public databases (e.g. PRINTS, BLOCKS, INTERPRO, PROSITE SWISSPROT). Data from experimental results and from the bioinformatic analysis are integrated and stored in a relational database (MS SQL-Server), which makes it possible for researchers to find answers to biological questions easily, thereby speeding up the selection of targets for further analysis. The designed pipeline constitutes a new automatic approach to obtaining and administrating relevant biological data from high-throughput investigations of cDNAs in order to systematically identify and characterize novel genes, as well as to comprehensively describe the function of the encoded proteins.

Automation↗

PubMed2004

LIFEdb: a database for functional genomics experiments integrating information from external sources, and serving as a sample tracking system.

We have implemented LIFEdb (http://www.dkfz.de/LIFEdb) to link information regarding novel human full-length cDNAs generated and sequenced by the German cDNA Consortium with functional information on the encoded proteins produced in functional genomics and proteomics approaches. The database also serves as a sample-tracking system to manage the process from cDNA to experimental read-out and data interpretation. A web interface enables the scientific community to explore and visualize features of the annotated cDNAs and ORFs combined with experimental results, and thus helps to unravel new features of proteins with as yet unknown functions.

Automation↗

PubMed2003

cDNA2Genome: a tool for mapping and annotating cDNAs.

BACKGROUND: In the last years several high-throughput cDNA sequencing projects have been funded worldwide with the aim of identifying and characterizing the structure of complete novel human transcripts. However some of these cDNAs are error prone due to frameshifts and stop codon errors caused by low sequence quality, or to cloning of truncated inserts, among other reasons. Therefore, accurate CDS prediction from these sequences first require the identification of potentially problematic cDNAs in order to speed up the posterior annotation process. RESULTS: cDNA2Genome is an application for the automatic high-throughput mapping and characterization of cDNAs. It utilizes current annotation data and the most up to date databases, especially in the case of ESTs and mRNAs in conjunction with a vast number of approaches to gene prediction in order to perform a comprehensive assessment of the cDNA exon-intron structure. The final result of cDNA2Genome is an XML file containing all relevant information obtained in the process. This XML output can easily be used for further analysis such us program pipelines, or the integration of results into databases. The web interface to cDNA2Genome also presents this data in HTML, where the annotation is additionally shown in a graphical form. cDNA2Genome has been implemented under the W3H task framework which allows the combination of bioinformatics tools in tailor-made analysis task flows as well as the sequential or parallel computation of many sequences for large-scale analysis. CONCLUSIONS: cDNA2Genome represents a new versatile and easily extensible approach to the automated mapping and annotation of human cDNAs. The underlying approach allows sequential or parallel computation of sequences for high-throughput analysis of cDNAs.

Chromosome Mapping↗

PubMed2003

ESTAnnotator: A tool for high throughput EST annotation.

In high throughput sequence analysis, it is often necessary to combine the results of contemporary bioinformatics tools, because no individual tool alone computes all the requested information. ESTAnnotator is a tool for the high throughput annotation of expressed sequence tags (ESTs) by automatically running a collection of bioinformatics applications. In the first step, a quality check is performed and repeats, vector parts and low quality sequences are masked. Then successive steps of database searching and EST clustering are performed. Already known transcripts present within mRNA and genomic DNA reference databases are identified. Subsequently, tools for the clustering of anonymous ESTs, and for further database searches at the protein level, are applied. Finally, the outputs of each individual tool are gathered and the relevant results presented in a descriptive summary. ESTAnnotator was already successfully applied for the systematic identification and characterisation of novel human genes involved in cartilage/bone formation, growth, differentiation and homeostasis. ESTAnnotator is available at http://genome.dkfz-heidelberg.de, contact: genome@dkfz.de.

Cartilage↗

PubMed2003

A task framework for the web interface W2H.

SUMMARY: The W3H task framework allows the execution of compound jobs utilizing the description of work and data flows in a heterogeneous bioinformatics environment using meta-data information. By means of these descriptions, the task system can schedule the necessary execution of applications available in the environment, depending on rules specified in the meta-data. By integrating this task framework into the publicly available web interface W2H, similarly based on meta-data, web access and data management are immediately available for each task description. Authors of task descriptions can base their work on the underlying classes and objects to be able to describe dependency rules between previously independent applications. The result of a compound task is given as XML data that is translated according to XSLT data into web pages or plain text to report the result of the task to the user. AVAILABILITY: Within the HUSAR environment at DKFZ http://genome.dkfz-heidelberg.de/

Database Management Systems↗

PubMed2002

PATH: a task for the inference of phylogenies.

UNLABELLED: Phylogenetic Analysis Task in Husar (PATH) is a task for the inference of phylogenies. It executes three phylogenetic methods and automatically chooses the evolutionary model for each set of data. The output of the tasks shows the consensus trees together with full results obtained from all executed methods. AVAILABILITY: PATH is available at the German EMBnet node after registration via www at http://genome.dkfz-heidelberg.de

Databases, Nucleic Acid↗