Disease and phenotype data at Ensembl.

Biological databases are an important resource for the life sciences community. Accessing the hundreds of databases supporting molecular biology and related fields is a daunting and time-consuming task. Integrating this information into one access point is a necessity for the life sciences community, which includes researchers focusing on human disease. Here we discuss the Ensembl genome browser, which acts as a single entry point with Graphical User Interface to data from multiple projects, including OMIM, dbSNP, and the NHGRI GWAS catalog. Ensembl provides a comprehensive source of annotation for the human genome, along with other species of biomedical interest. In this unit, we explore how to use the Ensembl genome browser in example queries related to human genetic diseases. Support protocols demonstrate quick sequence export using the BioMart tool.

Ensembl variation resources.

BACKGROUND: The maturing field of genomics is rapidly increasing the number of sequenced genomes and producing more information from those previously sequenced. Much of this additional information is variation data derived from sampling multiple individuals of a given species with the goal of discovering new variants and characterising the population frequencies of the variants that are already known. These data have immense value for many studies, including those designed to understand evolution and connect genotype to phenotype. Maximising the utility of the data requires that it be stored in an accessible manner that facilitates the integration of variation data with other genome resources such as gene annotation and comparative genomics. DESCRIPTION: The Ensembl project provides comprehensive and integrated variation resources for a wide variety of chordate genomes. This paper provides a detailed description of the sources of data and the methods for creating the Ensembl variation databases. It also explores the utility of the information by explaining the range of query options available, from using interactive web displays, to online data mining tools and connecting directly to the data servers programmatically. It gives a good overview of the variation resources and future plans for expanding the variation data within Ensembl. CONCLUSIONS: Variation data is an important key to understanding the functional and phenotypic differences between individuals. The development of new sequencing and genotyping technologies is greatly increasing the amount of variation data known for almost all genomes. The Ensembl variation resources are integrated into the Ensembl genome browser and provide a comprehensive way to access this data in the context of a widely used genome bioinformatics system. All Ensembl data is freely available at http://www.ensembl.org and from the public MySQL database server at ensembldb.ensembl.org.

Touring Ensembl: a practical guide to genome browsing.

The number of databases in molecular biological fields has rapidly increased to provide a large-scale resource. Though valuable information is available, data can be difficult to access, compare and integrate due to different formats and presentations of web interfaces. This paper offers a practical guide to the integration of gene, comparative genomic, and functional genomics data using the Ensembl website at http://www.ensembl.org.The Ensembl genome browser and underlying databases focus on chordate organisms. More species such as plants and microorganisms can be investigated using our sister browser at http://www.ensemblgenomes.org.In this study, four examples are used that sample many pages and features of the Ensembl browser. We focus on comparative studies across over 50 mostly chordate organisms, variations linked to disease, functional genomics, and access of external information housed in databases outside the Ensembl project. Researchers will learn how to go beyond simply exporting one gene sequence, and explore how a genome browser can integrate data from various sources and databases to build a full and comprehensive biological picture.

Destabilization of the Escherichia coli RNase H kinetic intermediate: switching between a two-state and three-state folding mechanism.

Escherichia coli RNase H folds through a partially folded kinetic intermediate that mirrors a rarely populated, partially unfolded form detectable by native-state hydrogen exchange under equilibrium conditions. Residue 53 is at the interface of two helices known to be structured in this intermediate. Kinetic refolding studies on mutant proteins varying in size and hydrophobicity at residue 53 support a contribution of hydrophobicity to the stabilities of the kinetic intermediate and the transition state. Packing interactions also play a significant role in the stability of these two states, though they play a much larger role in the native-state stability. One dramatic mutation, I53D, results in the conversion from a three-state to a two-state folding mechanism, which is explained most easily through a simple destabilization of the kinetic intermediate such that it is no longer stable with respect to the unfolded state. These results demonstrate that interactions that stabilize an intermediate can accelerate folding if these same interactions are present in the transition state. Our results are consistent with a hierarchical model of folding, where the intermediate consists of native-like interactions, is on-pathway, and is productive for folding.