BRCA Challenge: BRCA Exchange as a global resource for variants in BRCA1 and BRCA2.

The BRCA Challenge is a long-term data-sharing project initiated within the Global Alliance for Genomics and Health (GA4GH) to aggregate BRCA1 and BRCA2 data to support highly collaborative research activities. Its goal is to generate an informed and current understanding of the impact of genetic variation on cancer risk across the iconic cancer predisposition genes, BRCA1 and BRCA2. Initially, reported variants in BRCA1 and BRCA2 available from public databases were integrated into a single, newly created site, www.brcaexchange.org. The purpose of the BRCA Exchange is to provide the community with a reliable and easily accessible record of variants interpreted for a high-penetrance phenotype. More than 20,000 variants have been aggregated, three times the number found in the next-largest public database at the project's outset, of which approximately 7,250 have expert classifications. The data set is based on shared information from existing clinical databases-Breast Cancer Information Core (BIC), ClinVar, and the Leiden Open Variation Database (LOVD)-as well as population databases, all linked to a single point of access. The BRCA Challenge has brought together the existing international Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) consortium expert panel, along with expert clinicians, diagnosticians, researchers, and database providers, all with a common goal of advancing our understanding of BRCA1 and BRCA2 variation. Ongoing work includes direct contact with national centers with access to BRCA1 and BRCA2 diagnostic data to encourage data sharing, development of methods suitable for extraction of genetic variation at the level of individual laboratory reports, and engagement with participant communities to enable a more comprehensive understanding of the clinical significance of genetic variation in BRCA1 and BRCA2.

The UCSC Cancer Genomics Browser: update 2015.

The UCSC Cancer Genomics Browser (https://genome-cancer.ucsc.edu/) is a web-based application that integrates relevant data, analysis and visualization, allowing users to easily discover and share their research observations. Users can explore the relationship between genomic alterations and phenotypes by visualizing various -omic data alongside clinical and phenotypic features, such as age, subtype classifications and genomic biomarkers. The Cancer Genomics Browser currently hosts 575 public datasets from genome-wide analyses of over 227,000 samples, including datasets from TCGA, CCLE, Connectivity Map and TARGET. Users can download and upload clinical data, generate Kaplan-Meier plots dynamically, export data directly to Galaxy for analysis, plus generate URL bookmarks of specific views of the data to share with others.

The UCSC Cancer Genomics Browser: update 2013.

The UCSC Cancer Genomics Browser (https://genome-cancer.ucsc.edu/) is a set of web-based tools to display, investigate and analyse cancer genomics data and its associated clinical information. The browser provides whole-genome to base-pair level views of several different types of genomics data, including some next-generation sequencing platforms. The ability to view multiple datasets together allows users to make comparisons across different data and cancer types. Biological pathways, collections of genes, genomic or clinical information can be used to sort, aggregate and zoom into a group of samples. We currently display an expanding set of data from various sources, including 201 datasets from 22 TCGA (The Cancer Genome Atlas) cancers as well as data from Cancer Cell Line Encyclopedia and Stand Up To Cancer. New features include a completely redesigned user interface with an interactive tutorial and updated documentation. We have also added data downloads, additional clinical heatmap features, and an updated Tumor Image Browser based on Google Maps. New security features allow authenticated users access to private datasets hosted by several different consortia through the public website.

The UCSC Genome Browser database: extensions and updates 2013.

The University of California Santa Cruz (UCSC) Genome Browser (http://genome.ucsc.edu) offers online public access to a growing database of genomic sequence and annotations for a wide variety of organisms. The Browser is an integrated tool set for visualizing, comparing, analysing and sharing both publicly available and user-generated genomic datasets. As of September 2012, genomic sequence and a basic set of annotation 'tracks' are provided for 63 organisms, including 26 mammals, 13 non-mammal vertebrates, 3 invertebrate deuterostomes, 13 insects, 6 worms, yeast and sea hare. In the past year 19 new genome assemblies have been added, and we anticipate releasing another 28 in early 2013. Further, a large number of annotation tracks have been either added, updated by contributors or remapped to the latest human reference genome. Among these are an updated UCSC Genes track for human and mouse assemblies. We have also introduced several features to improve usability, including new navigation menus. This article provides an update to the UCSC Genome Browser database, which has been previously featured in the Database issue of this journal.

The UCSC Genome Browser database: extensions and updates 2011.

The University of California Santa Cruz Genome Browser (http://genome.ucsc.edu) offers online public access to a growing database of genomic sequence and annotations for a wide variety of organisms. The Browser is an integrated tool set for visualizing, comparing, analyzing and sharing both publicly available and user-generated genomic data sets. In the past year, the local database has been updated with four new species assemblies, and we anticipate another four will be released by the end of 2011. Further, a large number of annotation tracks have been either added, updated by contributors, or remapped to the latest human reference genome. Among these are new phenotype and disease annotations, UCSC genes, and a major dbSNP update, which required new visualization methods. Growing beyond the local database, this year we have introduced 'track data hubs', which allow the Genome Browser to provide access to remotely located sets of annotations. This feature is designed to significantly extend the number and variety of annotation tracks that are publicly available for visualization and analysis from within our site. We have also introduced several usability features including track search and a context-sensitive menu of options available with a right-click anywhere on the Browser's image.

ENCODE whole-genome data in the UCSC Genome Browser: update 2012.

The Encyclopedia of DNA Elements (ENCODE) Consortium is entering its 5th year of production-level effort generating high-quality whole-genome functional annotations of the human genome. The past year has brought the ENCODE compendium of functional elements to critical mass, with a diverse set of 27 biochemical assays now covering 200 distinct human cell types. Within the mouse genome, which has been under study by ENCODE groups for the past 2 years, 37 cell types have been assayed. Over 2000 individual experiments have been completed and submitted to the Data Coordination Center for public use. UCSC makes this data available on the quality-reviewed public Genome Browser (http://genome.ucsc.edu) and on an early-access Preview Browser (http://genome-preview.ucsc.edu). Visual browsing, data mining and download of raw and processed data files are all supported. An ENCODE portal (http://encodeproject.org) provides specialized tools and information about the ENCODE data sets.

The UCSC Cancer Genomics Browser: update 2011.

The UCSC Cancer Genomics Browser (https://genome-cancer.ucsc.edu) comprises a suite of web-based tools to integrate, visualize and analyze cancer genomics and clinical data. The browser displays whole-genome views of genome-wide experimental measurements for multiple samples alongside their associated clinical information. Multiple data sets can be viewed simultaneously as coordinated 'heatmap tracks' to compare across studies or different data modalities. Users can order, filter, aggregate, classify and display data interactively based on any given feature set including clinical features, annotated biological pathways and user-contributed collections of genes. Integrated standard statistical tools provide dynamic quantitative analysis within all available data sets. The browser hosts a growing body of publicly available cancer genomics data from a variety of cancer types, including data generated from the Cancer Genome Atlas project. Multiple consortiums use the browser on confidential prepublication data enabled by private installations. Many new features have been added, including the hgMicroscope tumor image viewer, hgSignature for real-time genomic signature evaluation on any browser track, and 'PARADIGM' pathway tracks to display integrative pathway activities. The browser is integrated with the UCSC Genome Browser; thus inheriting and integrating the Genome Browser's rich set of human biology and genetics data that enhances the interpretability of the cancer genomics data.

The UCSC Genome Browser database: update 2011.

The University of California, Santa Cruz Genome Browser (http://genome.ucsc.edu) offers online access to a database of genomic sequence and annotation data for a wide variety of organisms. The Browser also has many tools for visualizing, comparing and analyzing both publicly available and user-generated genomic data sets, aligning sequences and uploading user data. Among the features released this year are a gene search tool and annotation track drag-reorder functionality as well as support for BAM and BigWig/BigBed file formats. New display enhancements include overlay of multiple wiggle tracks through use of transparent coloring, options for displaying transformed wiggle data, a 'mean+whiskers' windowing function for display of wiggle data at high zoom levels, and more color schemes for microarray data. New data highlights include seven new genome assemblies, a Neandertal genome data portal, phenotype and disease association data, a human RNA editing track, and a zebrafish Conservation track. We also describe updates to existing tracks.

Evaluation of software impact designed for biomedical research: Are we measuring what's meaningful?

Software is vital for the advancement of biology and medicine. Through analysis of usage and impact metrics of software, developers can help determine user and community engagement. These metrics can be used to justify additional funding, encourage additional use, and identify unanticipated use cases. Such analyses can help define improvement areas and assist with managing project resources. However, there are challenges associated with assessing usage and impact, many of which vary widely depending on the type of software being evaluated. These challenges involve issues of distorted, exaggerated, understated, or misleading metrics, as well as ethical and security concerns. More attention to the nuances, challenges, and considerations involved in capturing impact across the diverse spectrum of biological software is needed. Furthermore, some tools may be especially beneficial to a small audience, yet may not have comparatively compelling metrics of high usage. Although some principles are generally applicable, there is not a single perfect metric or approach to effectively evaluate a software tool's impact, as this depends on aspects unique to each tool, how it is used, and how one wishes to evaluate engagement. We propose more broadly applicable guidelines (such as infrastructure that supports the usage of software and the collection of metrics about usage), as well as strategies for various types of software and resources. We also highlight outstanding issues in the field regarding how communities measure or evaluate software impact. To gain a deeper understanding of the issues hindering software evaluations, as well as to determine what appears to be helpful, we performed a survey of participants involved with scientific software projects for the Informatics Technology for Cancer Research (ITCR) program funded by the National Cancer Institute (NCI). We also investigated software among this scientific community and others to assess how often infrastructure that supports such evaluations is implemented and how this impacts rates of papers describing usage of the software. We find that although developers recognize the utility of analyzing data related to the impact or usage of their software, they struggle to find the time or funding to support such analyses. We also find that infrastructure such as social media presence, more in-depth documentation, the presence of software health metrics, and clear information on how to contact developers seem to be associated with increased usage rates. Our findings can help scientific software developers make the most out of the evaluations of their software so that they can more fully benefit from such assessments.

Making Tools that People Will Use: User-Centered Design in Computational Biology Research.

User-Centered Design (UCD) focuses on deeply understanding the needs of users and ensuring these needs are met by tools and software. UCD methodology aims to make tools easier to use, reduce time spent in development and the need for user support, as well as make it easier to create and maintain documentation. The goal of UCD is to ultimately make a tool that meets user needs and is a pleasure to use. This workshop will give an overview of UCD and several examples of how UCD practices are already being used at several institutions. Attendees will leave with ideas of how to incorporate UCD into their tool development as well as general resources to get started.

A user guide for the online exploration and visualization of PCAWG data.

The Pan-Cancer Analysis of Whole Genomes (PCAWG) project generated a vast amount of whole-genome cancer sequencing resource data. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumor types, we provide a user's guide to the five publicly available online data exploration and visualization tools introduced in the PCAWG marker paper. These tools are ICGC Data Portal, UCSC Xena, Chromothripsis Explorer, Expression Atlas, and PCAWG-Scout. We detail use cases and analyses for each tool, show how they incorporate outside resources from the larger genomics ecosystem, and demonstrate how the tools can be used together to understand the biology of cancers more deeply. Together, the tools enable researchers to query the complex genomic PCAWG data dynamically and integrate external information, enabling and enhancing interpretation.

Exploring TCGA Pan-Cancer data at the UCSC Cancer Genomics Browser.

The UCSC Cancer Genomics Browser (https://genome-cancer.ucsc.edu) offers interactive visualization and exploration of TCGA genomic, phenotypic, and clinical data, as produced by the Cancer Genome Atlas Research Network. Researchers can explore the impact of genomic alterations on phenotypes by visualizing gene and protein expression, copy number, DNA methylation, somatic mutation and pathway inference data alongside clinical features, Pan-Cancer subtype classifications and genomic biomarkers. Integrated Kaplan-Meier survival analysis helps investigators to assess survival stratification by any of the information.

Discovery and antibacterial activity of glabramycin A-C from Neosartorya glabra by an antisense strategy.

Treatment of drug-resistant bacteria is a significant unmet medical need. This challenge can be met only by the discovery and development of new antibiotics. Antisense technology is one of the newest discovery tools that provides enhanced sensitivity for detection of antibacterials, and has led to the discovery of a number of interesting new antibacterial natural products. Continued utilization of this technology led to the discovery of three new bicyclic lactones, glabramycins A-C, from a Neosartorya glabra strain. Glabramycin C showed strong antibiotic activity against Streptococcus pneumoniae (MIC 2 microg ml(-1)) and modest antibiotic activity against Staphylococcus aureus (MIC 16 microg ml(-1)). The isolation, structure, relative configuration and antibacterial activity, and plausible biogenesis of these compounds have been discussed.