MOTIVATION: The efficient and reproducible analysis of high-throughput sequencing datasets necessitates the development of methodical and robust computational pipelines that integrate established and bespoke bioinformatics analysis tools, often written in high-level programming languages such as Python. Despite the increasing availability of programming libraries for genomics, there is a noticeable lack of tools specifically focused on transcriptomics. Key tasks in this area include the association of gene features (e.g. transcript isoforms, introns or untranslated regions) with relevant subsections of (large) genomics datasets across diverse data formats, as well as efficient querying of these data based on genomic locations and annotation attributes. RESULTS: To address the needs of transcriptomics data analyses, we developed rnalib, a Python library designed for creating custom bioinformatics analysis methods. Built on existing Python libraries like pysam and pyBigWig, rnalib offers random access support, enabling efficient access to relevant subregions of large, genome-wide datasets. Rnalib extends the filtering and access capabilities of these libraries and includes additional checks to prevent common errors when integrating genomics datasets. The library is centred on an object-oriented Transcriptome class that provides methods for stepwise annotation of gene features with both, local and remote data sources. The rnalib Application Programming Interface cleanly separates immutable genomic locations from associated, mutable data, and offers a wide range of methods for iterating, querying, and exporting collated datasets. Rnalib establishes a fast, readable, reproducible, and robust framework for developing novel transcriptomics data analysis tools and methods. AVAILABILITY AND IMPLEMENTATION: Source code, documentation, and tutorials are available at https://github.com/popitsch/rnalib.

MOTIVATION: Clinical decision making is increasingly guided by accurate and recurrent determination of presence and frequency of (somatic) variants and their haplotype through panel sequencing of disease-relevant genomic regions. Haplotype calling (phasing), however, is difficult and error prone unless variants are located on the same read which limits the ability of short-read sequencing to detect, e.g. co-occurrence of drug-resistance variants. Long-read panel sequencing enables direct phasing of amplicon variants besides having multiple other benefits, however, high error rates of current technologies prevented their applicability in the past. RESULTS: We have developed Nanopanel2, a variant caller for Nanopore panel sequencing data. Nanopanel2 works directly on base-called FAST5 files and uses allele probability distributions and several other filters to robustly separate true from false positive (FP) calls. It effectively calls SNVs and INDELs with variant allele frequencies as low as 1% and 5%, respectively, and produces only few low-frequency false-positive calls (∼1 FP call with VAF<5% per kb amplicon). Haplotype compositions are then determined by direct phasing. Nanopanel2 is the first somatic variant caller for Nanopore data, enabling accurate, fast (turnaround <48 h) and cheap (sequencing costs ∼10$/sample) diagnostic workflows. AVAILABILITYAND IMPLEMENTATION: The data for this study have been deposited at zenodo.org under DOIs accession numbers 4110691 and 4110698. Nanopanel2 is open source and available at https://github.com/popitsch/nanopanel2. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

SUMMARY: Genomic interval sets are fundamental elements of genome annotation and are the output of countless bioinformatics applications. Nevertheless, tool support for the manual curation of these data is currently limited. We developed VARAN-GIE, an extension of the popular Integrative Genomics Viewer (IGV) that adds functionality to edit, annotate and merge genomic interval sets. Data can easily be shared with other users and imported/exported from/to multiple common data formats. AVAILABILITY AND IMPLEMENTATION: VARAN-GIE binary releases, source-code, user guides and tutorials are available at https://github.com/popitsch/varan-gie/.

MOTIVATION: The increasing adoption of clinical whole-genome resequencing (WGS) demands for highly accurate and reproducible variant calling (VC) methods. The observed discordance between state-of-the-art VC pipelines, however, indicates that the current practice still suffers from non-negligible numbers of false positive and negative SNV and INDEL calls that were shown to be enriched among discordant calls but also in genomic regions with low sequence complexity. RESULTS: Here, we describe our method ReliableGenome (RG) for partitioning genomes into high and low concordance regions with respect to a set of surveyed VC pipelines. Our method combines call sets derived by multiple pipelines from arbitrary numbers of datasets and interpolates expected concordance for genomic regions without data. By applying RG to 219 deep human WGS datasets, we demonstrate that VC concordance depends predominantly on genomic context rather than the actual sequencing data which manifests in high recurrence of regions that can/cannot be reliably genotyped by a single method. This enables the application of pre-computed regions to other data created with comparable sequencing technology and software. RG outperforms comparable efforts in predicting VC concordance and false positive calls in low-concordance regions which underlines its usefulness for variant filtering, annotation and prioritization. RG allows focusing resource-intensive algorithms (e.g. consensus calling methods) on the smaller, discordant share of the genome (20-30%) which might result in increased overall accuracy at reasonable costs. Our method and analysis of discordant calls may further be useful for development, benchmarking and optimization of VC algorithms and for the relative comparison of call sets between different studies/pipelines. AVAILABILITY AND IMPLEMENTATION: RG was implemented in Java, source code and binaries are freely available for non-commercial use at https://github.com/popitsch/wtchg-rg/ CONTACT: [email protected] information: Supplementary data are available at Bioinformatics online.

UNLABELLED: Current data formats for the representation of depth of coverage data (DOC), a central resource for interpreting, filtering or detecting novel features in high-throughput sequencing datasets, were primarily designed for visualization purposes. This limits their applicability in stand-alone analyses of these data, mainly owing to inaccurate representation or mediocre data compression. CODOC is a novel data format and comprehensive application programming interface for efficient representation, access and analysis of DOC data. CODOC compresses these data ∼ 4-32× better than the best current comparable method by exploiting specific data characteristics while at the same time enabling more-exact signal recovery for lossy compression and very fast query answering times. AVAILABILITY AND IMPLEMENTATION: Java source code and binaries are freely available for non-commercial use at http://purl.org/bgraph/codoc.

The Web of Data has emerged as a way of exposing structured linked data on the Web. It builds on the central building blocks of the Web (URIs, HTTP) and benefits from its simplicity and wide-spread adoption. It does, however, also inherit the unresolved issues such as the broken link problem. Broken links constitute a major challenge for actors consuming Linked Data as they require them to deal with reduced accessibility of data. We believe that the broken link problem is a major threat to the whole Web of Data idea and that both Linked Data consumers and providers will require solutions that deal with this problem. Since no general solutions for fixing such links in the Web of Data have emerged, we make three contributions into this direction: first, we provide a concise definition of the broken link problem and a comprehensive analysis of existing approaches. Second, we present DSNotify, a generic framework able to assist human and machine actors in fixing broken links. It uses heuristic feature comparison and employs a time-interval-based blocking technique for the underlying instance matching problem. Third, we derived benchmark datasets from knowledge bases such as DBpedia and evaluated the effectiveness of our approach with respect to the broken link problem. Our results show the feasibility of a time-interval-based blocking approach for systems that aim at detecting and fixing broken links in the Web of Data.

Current multimedia database systems largely focus on specific media types and/or application domains. This paper gives a sketch of METIS, a database solution for the unified management of any kind of digital media, characterized by profound customizability for domain or application needs. The system core is based on an expressive data model that can be adapted to any scheme for media management, description, and classification desired, and can accommodate arbitrary query operators, similarity measures, and/or feature extraction algorithms. METIS is based on a persistence abstraction layer allowing the exchange of storage back-ends and includes a customizable web front-end for media management. Thereby, METIS establishes a common database foundation for a wide spectrum of multimedia applications.