RESUMEN

BACKGROUND: Thoroughly annotated data resources are a key requirement in phenotype dependent analysis and diagnosis of diseases in the area of precision medicine. Recent work has shown that curation and systematic annotation of human phenome data can significantly improve the quality and selectivity for the interpretation of inherited diseases. We have therefore developed PhenoDis, a comprehensive, manually annotated database providing symptomatic, genetic and imprinting information about rare cardiac diseases. RESULTS: PhenoDis includes 214 rare cardiac diseases from Orphanet and 94 more from OMIM. For phenotypic characterization of the diseases, we performed manual annotation of diseases with articles from the biomedical literature. Detailed description of disease symptoms required the use of 2247 different terms from the Human Phenotype Ontology (HPO). Diseases listed in PhenoDis frequently cover a broad spectrum of symptoms with 28% from the branch of 'cardiovascular abnormality' and others from areas such as neurological (11.5%) and metabolism (6%). We collected extensive information on the frequency of symptoms in respective diseases as well as on disease-associated genes and imprinting data. The analysis of the abundance of symptoms in patient studies revealed that most of the annotated symptoms (71%) are found in less than half of the patients of a particular disease. Comprehensive and systematic characterization of symptoms including their frequency is a pivotal prerequisite for computer based prediction of diseases and disease causing genetic variants. To this end, PhenoDis provides in-depth annotation for a complete group of rare diseases, including information on pathogenic and likely pathogenic genetic variants for 206 diseases as listed in ClinVar. We integrated all results in an online database ( http://mips.helmholtz-muenchen.de/phenodis/ ) with multiple search options and provide the complete dataset for download. CONCLUSION: PhenoDis provides a comprehensive set of manually annotated rare cardiac diseases that enables computational approaches for disease prediction via decision support systems and phenotype-driven strategies for the identification of disease causing genes.

Asunto(s)

Cardiopatías/genética , Cardiopatías/patología , Enfermedades Raras/genética , Enfermedades Raras/patología , Biología Computacional/métodos , Bases de Datos Genéticas , Variación Genética/genética , Genómica/métodos , Cardiopatías/metabolismo , Humanos , Fenotipo , Medicina de Precisión/métodos , Enfermedades Raras/metabolismo

RESUMEN

Summary: Analysis of Next Generation Sequencing (NGS) data requires the processing of large datasets by chaining various tools with complex input and output formats. In order to automate data analysis, we propose to standardize NGS tasks into modular workflows. This simplifies reliable handling and processing of NGS data, and corresponding solutions become substantially more reproducible and easier to maintain. Here, we present a documented, linux-based, toolbox of 42 processing modules that are combined to construct workflows facilitating a variety of tasks such as DNAseq and RNAseq analysis. We also describe important technical extensions. The high throughput executor (HTE) helps to increase the reliability and to reduce manual interventions when processing complex datasets. We also provide a dedicated binary manager that assists users in obtaining the modules' executables and keeping them up to date. As basis for this actively developed toolbox we use the workflow management software KNIME. Availability and Implementation: See http://ibisngs.github.io/knime4ngs for nodes and user manual (GPLv3 license). Contact: robert.kueffner@helmholtz-muenchen.de. Supplementary information: Supplementary data are available at Bioinformatics online.

Asunto(s)

Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Programas Informáticos , Reproducibilidad de los Resultados , Flujo de Trabajo

RESUMEN

The Munich Information Center for Protein Sequences (MIPS at the Helmholtz Center for Environmental Health, Neuherberg, Germany) has many years of experience in providing annotated collections of biological data. Selected data sets of high relevance, such as model genomes, are subjected to careful manual curation, while the bulk of high-throughput data is annotated by automatic means. High-quality reference resources developed in the past and still actively maintained include Saccharomyces cerevisiae, Neurospora crassa and Arabidopsis thaliana genome databases as well as several protein interaction data sets (MPACT, MPPI and CORUM). More recent projects are PhenomiR, the database on microRNA-related phenotypes, and MIPS PlantsDB for integrative and comparative plant genome research. The interlinked resources SIMAP and PEDANT provide homology relationships as well as up-to-date and consistent annotation for 38,000,000 protein sequences. PPLIPS and CCancer are versatile tools for proteomics and functional genomics interfacing to a database of compilations from gene lists extracted from literature. A novel literature-mining tool, EXCERBT, gives access to structured information on classified relations between genes, proteins, phenotypes and diseases extracted from Medline abstracts by semantic analysis. All databases described here, as well as the detailed descriptions of our projects can be accessed through the MIPS WWW server (http://mips.helmholtz-muenchen.de).

Asunto(s)

Bases de Datos Genéticas , Minería de Datos , Bases de Datos de Proteínas , Genes Relacionados con las Neoplasias , Genoma de Planta , Genómica , Metabolómica , MicroARNs/metabolismo , Fenotipo , Proteómica , Análisis de Secuencia de Proteína , Integración de Sistemas

RESUMEN

CORUM is a database that provides a manually curated repository of experimentally characterized protein complexes from mammalian organisms, mainly human (64%), mouse (16%) and rat (12%). Protein complexes are key molecular entities that integrate multiple gene products to perform cellular functions. The new CORUM 2.0 release encompasses 2837 protein complexes offering the largest and most comprehensive publicly available dataset of mammalian protein complexes. The CORUM dataset is built from 3198 different genes, representing approximately 16% of the protein coding genes in humans. Each protein complex is described by a protein complex name, subunit composition, function as well as the literature reference that characterizes the respective protein complex. Recent developments include mapping of functional annotation to Gene Ontology terms as well as cross-references to Entrez Gene identifiers. In addition, a 'Phylogenetic Conservation' analysis tool was implemented that analyses the potential occurrence of orthologous protein complex subunits in mammals and other selected groups of organisms. This allows one to predict the occurrence of protein complexes in different phylogenetic groups. CORUM is freely accessible at (http://mips.helmholtz-muenchen.de/genre/proj/corum/index.html).

Asunto(s)

Biología Computacional/métodos , Bases de Datos Genéticas , Bases de Datos de Proteínas , Complejos Multiproteicos , Animales , Biología Computacional/tendencias , Humanos , Almacenamiento y Recuperación de la Información/métodos , Internet , Ratones , Filogenia , Estructura Terciaria de Proteína , Ratas , Saccharomyces cerevisiae/genética , Programas Informáticos

RESUMEN

UNLABELLED: Cross-mapping of gene and protein identifiers between different databases is a tedious and time-consuming task. To overcome this, we developed CRONOS, a cross-reference server that contains entries from five mammalian organisms presented by major gene and protein information resources. Sequence similarity analysis of the mapped entries shows that the cross-references are highly accurate. In total, up to 18 different identifier types can be used for identification of cross-references. The quality of the mapping could be improved substantially by exclusion of ambiguous gene and protein names which were manually validated. Organism-specific lists of ambiguous terms, which are valuable for a variety of bioinformatics applications like text mining are available for download. AVAILABILITY: CRONOS is freely available to non-commercial users at http://mips.gsf.de/genre/proj/cronos/index.html, web services are available at http://mips.gsf.de/CronosWSService/CronosWS?wsdl.

Asunto(s)

Biología Computacional/instrumentación , Biología Computacional/métodos , Internet , Programas Informáticos , Animales , Genes , Humanos , Proteínas

RESUMEN

The generation of expressed sequence tag (EST) libraries offers an affordable approach to investigate organisms, if no genome sequence is available. OREST (http://mips.gsf.de/genre/proj/orest/index.html) is a server-based EST analysis pipeline, which allows the rapid analysis of large amounts of ESTs or cDNAs from mammalia and fungi. In order to assign the ESTs to genes or proteins OREST maps DNA sequences to reference datasets of gene products and in a second step to complete genome sequences. Mapping against genome sequences recovers additional 13% of EST data, which otherwise would escape further analysis. To enable functional analysis of the datasets, ESTs are functionally annotated using the hierarchical FunCat annotation scheme as well as GO annotation terms. OREST also allows to predict the association of gene products and diseases by Morbid Map (OMIM) classification. A statistical analysis of the results of the dataset is possible with the included PROMPT software, which provides information about enrichment and depletion of functional and disease annotation terms. OREST was successfully applied for the identification and functional characterization of more than 3000 EST sequences of the common marmoset monkey (Callithrix jacchus) as part of an international collaboration.

Asunto(s)

Etiquetas de Secuencia Expresada/química , Programas Informáticos , Animales , Mapeo Cromosómico , Genes Fúngicos , Humanos , Internet , Mamíferos/genética , Ratones , Proteínas/genética , Ratas , Saccharomyces cerevisiae/genética , Análisis de Secuencia de ADN

RESUMEN

Protein complexes are key molecular entities that integrate multiple gene products to perform cellular functions. The CORUM (http://mips.gsf.de/genre/proj/corum/index.html) database is a collection of experimentally verified mammalian protein complexes. Information is manually derived by critical reading of the scientific literature from expert annotators. Information about protein complexes includes protein complex names, subunits, literature references as well as the function of the complexes. For functional annotation, we use the FunCat catalogue that enables to organize the protein complex space into biologically meaningful subsets. The database contains more than 1750 protein complexes that are built from 2400 different genes, thus representing 12% of the protein-coding genes in human. A web-based system is available to query, view and download the data. CORUM provides a comprehensive dataset of protein complexes for discoveries in systems biology, analyses of protein networks and protein complex-associated diseases. Comparable to the MIPS reference dataset of protein complexes from yeast, CORUM intends to serve as a reference for mammalian protein complexes.

Asunto(s)

Bases de Datos de Proteínas , Complejos Multiproteicos/fisiología , Animales , Humanos , Internet , Ratones , Complejos Multiproteicos/análisis , Complejos Multiproteicos/química , Ratas , Interfaz Usuario-Computador

RESUMEN

Similarity Matrix of Proteins (SIMAP) (http://mips.gsf.de/simap) provides a database based on a pre-computed similarity matrix covering the similarity space formed by >4 million amino acid sequences from public databases and completely sequenced genomes. The database is capable of handling very large datasets and is updated incrementally. For sequence similarity searches and pairwise alignments, we implemented a grid-enabled software system, which is based on FASTA heuristics and the Smith-Waterman algorithm. Our ProtInfo system allows querying by protein sequences covered by the SIMAP dataset as well as by fragments of these sequences, highly similar sequences and title words. Each sequence in the database is supplemented with pre-calculated features generated by detailed sequence analyses. By providing WWW interfaces as well as web-services, we offer the SIMAP resource as an efficient and comprehensive tool for sequence similarity searches.

Asunto(s)

Bases de Datos de Proteínas , Homología de Secuencia de Aminoácido , Internet , Alineación de Secuencia , Programas Informáticos , Interfaz Usuario-Computador

RESUMEN

MfunGD (http://mips.gsf.de/genre/proj/mfungd/) provides a resource for annotated mouse proteins and their occurrence in protein networks. Manual annotation concentrates on proteins which are found to interact physically with other proteins. Accordingly, manually curated information from a protein-protein interaction database (MPPI) and a database of mammalian protein complexes is interconnected with MfunGD. Protein function annotation is performed using the Functional Catalogue (FunCat) annotation scheme which is widely used for the analysis of protein networks. The dataset is also supplemented with information about the literature that was used in the annotation process as well as links to the SIMAP Fasta database, the Pedant protein analysis system and cross-references to external resources. Proteins that so far were not manually inspected are annotated automatically by a graphical probabilistic model and/or superparamagnetic clustering. The database is continuously expanding to include the rapidly growing amount of functional information about gene products from mouse. MfunGD is implemented in GenRE, a J2EE-based component-oriented multi-tier architecture following the separation of concern principle.

Asunto(s)

Bases de Datos Genéticas , Genómica , Ratones/genética , Complejos Multiproteicos/genética , Complejos Multiproteicos/fisiología , Animales , Internet , Complejos Multiproteicos/química , Proteómica , Programas Informáticos , Interfaz Usuario-Computador

RESUMEN

Data from large-scale genome projects, transcriptomics and proteomics experiments have provided scientists with a wealth of information establishing the basis for the investigation of cellular processes. To understand biological function beyond the single gene by the discovery and characterization of functional protein networks, bioinformatics analysis requires information about two additional attributes associated with the gene products: (i) high-level protein function prediction of experimentally uncharacterized proteins and (ii) systematic classification of protein function. This article describes the basic properties of protein classification systems and discusses examples of their implementation.:

RESUMEN

In this paper, we present the Functional Catalogue (FunCat), a hierarchically structured, organism-independent, flexible and scalable controlled classification system enabling the functional description of proteins from any organism. FunCat has been applied for the manual annotation of prokaryotes, fungi, plants and animals. We describe how FunCat is implemented as a highly efficient and robust tool for the manual and automatic annotation of genomic sequences. Owing to its hierarchical architecture, FunCat has also proved to be useful for many subsequent downstream bioinformatic applications. This is illustrated by the analysis of large-scale experiments from various investigations in transcriptomics and proteomics, where FunCat was used to project experimental data into functional units, as 'gold standard' for functional classification methods, and also served to compare the significance of different experimental methods. Over the last decade, the FunCat has been established as a robust and stable annotation scheme that offers both, meaningful and manageable functional classification as well as ease of perception.

Asunto(s)

Biología Computacional/métodos , Genoma , Proteínas/clasificación , Proteínas/metabolismo , Proteómica/métodos , Programas Informáticos , Indización y Redacción de Resúmenes , Animales , Automatización/instrumentación , Automatización/métodos , Biología Computacional/instrumentación , Genómica/instrumentación , Genómica/métodos , Internet , Unión Proteica , Proteínas/genética , Proteoma/clasificación , Proteoma/genética , Proteoma/metabolismo , Proteómica/instrumentación , Reproducibilidad de los Resultados , Saccharomyces cerevisiae/química , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/clasificación , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Terminología como Asunto , Transcripción Genética/genética

RESUMEN

The German Neurospora Genome Project has assembled sequences from ordered cosmid and BAC clones of linkage groups II and V of the genome of Neurospora crassa in 13 and 12 contigs, respectively. Including additional sequences located on other linkage groups a total of 12 Mb were subjected to a manual gene extraction and annotation process. The genome comprises a small number of repetitive elements, a low degree of segmental duplications and very few paralogous genes. The analysis of the 3218 identified open reading frames provides a first overview of the protein equipment of a filamentous fungus. Significantly, N.crassa possesses a large variety of metabolic enzymes including a substantial number of enzymes involved in the degradation of complex substrates as well as secondary metabolism. While several of these enzymes are specific for filamentous fungi many are shared exclusively with prokaryotes.

Asunto(s)

Genoma Fúngico , Neurospora crassa/genética , Mapeo Cromosómico , Cromosomas Fúngicos/genética , ADN de Hongos/química , ADN de Hongos/genética , Bases de Datos de Ácidos Nucleicos , Internet , Sistemas de Lectura Abierta/genética , Filogenia , Análisis de Secuencia de ADN

RESUMEN

After 50 years of analysing Neurospora crassa genes one by one large scale sequence analysis has increased the number of accessible genes tremendously in the last few years. Being the only filamentous fungus for which a comprehensive genomic sequence database is publicly accessible N. crassa serves as the model for this important group of microorganisms. The MIPS N. crassa database currently holds more than 16 Mb of non-redundant data of the chromosomes II and V analysed by the German Neurospora Genome Project. This represents more than one-third of the genome. Open reading frames (ORFs) have been extracted from the sequence and the deduced proteins have been annotated extensively. They are classified according to matches in sequence databases and attributed to functional categories according to their relatives. While 41% of analysed proteins are related to known proteins, 30% are hypothetical proteins with no match to a database entry. The entire genome is expected to comprise some 13000 protein coding genes, more than twice as many as found in yeasts, and reflects the high potential of filamentous fungi to cope with various environmental conditions.

Asunto(s)

Genoma Fúngico , Neurospora crassa/genética , Biotecnología , ADN Complementario/genética , ADN de Hongos/genética , Bases de Datos Genéticas , Proteínas Fúngicas/genética , Modelos Genéticos , Sistemas de Lectura Abierta , Análisis de Secuencia de ADN