SUMMARY: A main task in computational cancer analysis is the identification of patient subgroups (i.e. cohorts) based on metadata attributes (patient stratification) or genomic markers of response (biomarkers). Coral is a web-based cohort analysis tool that is designed to support this task: Users can interactively create and refine cohorts, which can then be compared, characterized and inspected down to the level of single items. Coral visualizes the evolution of cohorts and also provides intuitive access to prevalence information. Furthermore, findings can be stored, shared and reproduced via the integrated session management. Coral is pre-loaded with data from over 128 000 samples from the AACR Project GENIE, the Cancer Genome Atlas and the Cell Line Encyclopedia. AVAILABILITY AND IMPLEMENTATION: Coral is publicly available at https://coral.caleydoapp.org. The source code is released at https://github.com/Caleydo/coral. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

SUMMARY: Ordino is a web-based analysis tool for cancer genomics that allows users to flexibly rank, filter and explore genes, cell lines and tissue samples based on pre-loaded data, including The Cancer Genome Atlas, the Cancer Cell Line Encyclopedia and manually uploaded information. Interactive tabular data visualization that facilitates the user-driven prioritization process forms a core component of Ordino. Detail views of selected items complement the exploration. Findings can be stored, shared and reproduced via the integrated session management. AVAILABILITY AND IMPLEMENTATION: Ordino is publicly available at https://ordino.caleydoapp.org. The source code is released at https://github.com/Caleydo/ordino under the Mozilla Public License 2.0. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Storing analytical provenance generates a knowledge base with a large potential for recalling previous results and guiding users in future analyses. However, without extensive manual creation of meta information and annotations by the users, search and retrieval of analysis states can become tedious. We present KnowledgePearls, a solution for efficient retrieval of analysis states that are structured as provenance graphs containing automatically recorded user interactions and visualizations. As a core component, we describe a visual interface for querying and exploring analysis states based on their similarity to a partial definition of a requested analysis state. Depending on the use case, this definition may be provided explicitly by the user by formulating a search query or inferred from given reference states. We explain our approach using the example of efficient retrieval of demographic analyses by Hans Rosling and discuss our implementation for a fast look-up of previous states. Our approach is independent of the underlying visualization framework. We discuss the applicability for visualizations which are based on the declarative grammar Vega and we use a Vega-based implementation of Gapminder as guiding example. We additionally present a biomedical case study to illustrate how KnowledgePearls facilitates the exploration process by recalling states from earlier analyses.

MOTIVATION: The discovery of genomic structural variants (SVs) at high sensitivity and specificity is an essential requirement for characterizing naturally occurring variation and for understanding pathological somatic rearrangements in personal genome sequencing data. Of particular interest are integrated methods that accurately identify simple and complex rearrangements in heterogeneous sequencing datasets at single-nucleotide resolution, as an optimal basis for investigating the formation mechanisms and functional consequences of SVs. RESULTS: We have developed an SV discovery method, called DELLY, that integrates short insert paired-ends, long-range mate-pairs and split-read alignments to accurately delineate genomic rearrangements at single-nucleotide resolution. DELLY is suitable for detecting copy-number variable deletion and tandem duplication events as well as balanced rearrangements such as inversions or reciprocal translocations. DELLY, thus, enables to ascertain the full spectrum of genomic rearrangements, including complex events. On simulated data, DELLY compares favorably to other SV prediction methods across a wide range of sequencing parameters. On real data, DELLY reliably uncovers SVs from the 1000 Genomes Project and cancer genomes, and validation experiments of randomly selected deletion loci show a high specificity. AVAILABILITY: DELLY is available at www.korbel.embl.de/software.html CONTACT: [email protected].

Copy-number variations (CNVs) are widespread in the human genome, but comprehensive assignments of integer locus copy-numbers (i.e., copy-number genotypes) that, for example, enable discrimination of homozygous from heterozygous CNVs, have remained challenging. Here we present CopySeq, a novel computational approach with an underlying statistical framework that analyzes the depth-of-coverage of high-throughput DNA sequencing reads, and can incorporate paired-end and breakpoint junction analysis based CNV-analysis approaches, to infer locus copy-number genotypes. We benchmarked CopySeq by genotyping 500 chromosome 1 CNV regions in 150 personal genomes sequenced at low-coverage. The assessed copy-number genotypes were highly concordant with our performed qPCR experiments (Pearson correlation coefficient 0.94), and with the published results of two microarray platforms (95-99% concordance). We further demonstrated the utility of CopySeq for analyzing gene regions enriched for segmental duplications by comprehensively inferring copy-number genotypes in the CNV-enriched >800 olfactory receptor (OR) human gene and pseudogene loci. CopySeq revealed that OR loci display an extensive range of locus copy-numbers across individuals, with zero to two copies in some OR loci, and two to nine copies in others. Among genetic variants affecting OR loci we identified deleterious variants including CNVs and SNPs affecting ~15% and ~20% of the human OR gene repertoire, respectively, implying that genetic variants with a possible impact on smell perception are widespread. Finally, we found that for several OR loci the reference genome appears to represent a minor-frequency variant, implying a necessary revision of the OR repertoire for future functional studies. CopySeq can ascertain genomic structural variation in specific gene families as well as at a genome-wide scale, where it may enable the quantitative evaluation of CNVs in genome-wide association studies involving high-throughput sequencing.

UNLABELLED: Faspad is a user-friendly tool that detects candidates for linear signaling pathways in protein interaction networks based on an approach by Scott et al. (Journal of Computational Biology, 2006). Using recent algorithmic insights, it can solve the underlying NP-hard problem quite fast: for protein networks of typical size (several thousand nodes), pathway candidates of length up to 13 proteins can be found within seconds and with a 99.9% probability of optimality. Faspad graphically displays all candidates that are found; for evaluation and comparison purposes, an overlay of several candidates and the surrounding network context can also be shown. AVAILABILITY: Faspad is available as free software under the GPL license at http://theinf1.informatik.uni-jena.de/faspad/ and runs under Linux and Windows.