SUMMARY: Bioinformatics research frequently involves handling gene-centric data such as exons, transcripts, proteins and their positions relative to a reference coordinate system. The ensembldb Bioconductor package retrieves and stores Ensembl-based genetic annotations and positional information, and furthermore offers identifier conversion and coordinates mappings for gene-associated data. In support of reproducible research, data are tied to Ensembl releases and are kept separately from the software. Premade data packages are available for a variety of genomes and Ensembl releases. Three examples demonstrate typical use cases of this software. AVAILABILITY AND IMPLEMENTATION: ensembldb is part of Bioconductor (https://bioconductor.org/packages/ensembldb). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Motivation: Familial aggregation analysis is an important early step for characterizing the genetic determinants of phenotypes in epidemiological studies. To facilitate this analysis, a collection of methods to detect familial aggregation in large pedigrees has been made available recently. However, efficacy of these methods in real world scenarios remains largely unknown. Here, we assess the performance of five aggregation methods to identify individuals or groups of related individuals affected by a Mendelian trait within a large set of decoys. We investigate method performance under a representative set of combinations of causal variant penetrance, trait prevalence and number of affected generations in the pedigree. These methods are then applied to assess familial aggregation of familial hypercholesterolemia and stroke, in the context of the Cooperative Health Research in South Tyrol (CHRIS) study. Results: We find that in some situations statistical hypothesis testing with a binomial null distribution achieves performance similar to methods that are based on kinship information, while kinship based methods perform better when information is available on fewer generations. Potential case families from the CHRIS study are reported and the results are discussed taking into account insights from the performance assessment. Availability and implementation: The familial aggregation analysis package is freely available at the Bioconductor repository, http://www.bioconductor.org/packages/FamAgg. Supplementary information: Supplementary data are available at Bioinformatics online.

UNLABELLED: Familial aggregation analysis is the first fundamental step to perform when assessing the extent of genetic background of a disease. However, there is a lack of software to analyze the familial clustering of complex phenotypes in very large pedigrees. Such pedigrees can be utilized to calculate measures that express trait aggregation on both the family and individual level, providing valuable directions in choosing families for detailed follow-up studies. We developed FamAgg, an open source R package that contains both established and novel methods to investigate familial aggregation of traits in large pedigrees. We demonstrate its use and interpretation by analyzing a publicly available cancer dataset with more than 20 000 participants distributed across approximately 400 families. AVAILABILITY AND IMPLEMENTATION: The FamAgg package is freely available at the Bioconductor repository, http://www.bioconductor.org/packages/FamAgg CONTACT: [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

UNLABELLED: Three dimensional structures of proteins contain errors which often originate from limitations of the experimental techniques employed. Such errors frequently result in unfavorable atomic interactions. Here we present a new web service, called Interaction Viewer, for the visualization and correction of such errors. We show how the Interaction Viewer is used in combination with the NQ-Flipper service to spot strained asparagine and glutamine rotamers and we emphasize the convenience of this service in correcting such errors. AVAILABILITY: The web service is integrated with the NQ-Flipper service and accessible at http://flipper.services.came.sbg.ac.at

Abstract Summary: The error rate of asparagine (Asn) and glutamine (Gln) amide rotamers in protein crystal structures is in the order of 20% and as a consequence the current Protein Database (PDB) contains approximately half a million incorrect Asn and Gln side-chain rotamers. Here we present NQ-Flipper, a web service based on knowledge-based potentials of mean force to automatically detect and correct erroneous rotamers. We achieve excellent agreement with expert curated data. Availability: The program is accessible freely as a web service at Contact: [email protected]