COSMIC: the Catalogue Of Somatic Mutations In Cancer.

COSMIC, the Catalogue Of Somatic Mutations In Cancer (https://cancer.sanger.ac.uk) is the most detailed and comprehensive resource for exploring the effect of somatic mutations in human cancer. The latest release, COSMIC v86 (August 2018), includes almost 6 million coding mutations across 1.4 million tumour samples, curated from over 26 000 publications. In addition to coding mutations, COSMIC covers all the genetic mechanisms by which somatic mutations promote cancer, including non-coding mutations, gene fusions, copy-number variants and drug-resistance mutations. COSMIC is primarily hand-curated, ensuring quality, accuracy and descriptive data capture. Building on our manual curation processes, we are introducing new initiatives that allow us to prioritize key genes and diseases, and to react more quickly and comprehensively to new findings in the literature. Alongside improvements to the public website and data-download systems, new functionality in COSMIC-3D allows exploration of mutations within three-dimensional protein structures, their protein structural and functional impacts, and implications for druggability. In parallel with COSMIC's deep and broad variant coverage, the Cancer Gene Census (CGC) describes a curated catalogue of genes driving every form of human cancer. Currently describing 719 genes, the CGC has recently introduced functional descriptions of how each gene drives disease, summarized into the 10 cancer Hallmarks.

COSMIC: somatic cancer genetics at high-resolution.

COSMIC, the Catalogue of Somatic Mutations in Cancer (http://cancer.sanger.ac.uk) is a high-resolution resource for exploring targets and trends in the genetics of human cancer. Currently the broadest database of mutations in cancer, the information in COSMIC is curated by expert scientists, primarily by scrutinizing large numbers of scientific publications. Over 4 million coding mutations are described in v78 (September 2016), combining genome-wide sequencing results from 28 366 tumours with complete manual curation of 23 489 individual publications focused on 186 key genes and 286 key fusion pairs across all cancers. Molecular profiling of large tumour numbers has also allowed the annotation of more than 13 million non-coding mutations, 18 029 gene fusions, 187 429 genome rearrangements, 1 271 436 abnormal copy number segments, 9 175 462 abnormal expression variants and 7 879 142 differentially methylated CpG dinucleotides. COSMIC now details the genetics of drug resistance, novel somatic gene mutations which allow a tumour to evade therapeutic cancer drugs. Focusing initially on highly characterized drugs and genes, COSMIC v78 contains wide resistance mutation profiles across 20 drugs, detailing the recurrence of 301 unique resistance alleles across 1934 drug-resistant tumours. All information from the COSMIC database is available freely on the COSMIC website.

FlyBase at 25: looking to the future.

Since 1992, FlyBase (flybase.org) has been an essential online resource for the Drosophila research community. Concentrating on the most extensively studied species, Drosophila melanogaster, FlyBase includes information on genes (molecular and genetic), transgenic constructs, phenotypes, genetic and physical interactions, and reagents such as stocks and cDNAs. Access to data is provided through a number of tools, reports, and bulk-data downloads. Looking to the future, FlyBase is expanding its focus to serve a broader scientific community. In this update, we describe new features, datasets, reagent collections, and data presentations that address this goal, including enhanced orthology data, Human Disease Model Reports, protein domain search and visualization, concise gene summaries, a portal for external resources, video tutorials and the FlyBase Community Advisory Group.

FlyBase 102--advanced approaches to interrogating FlyBase.

FlyBase (http://flybase.org) is the leading website and database of Drosophila genes and genomes. Whether you are using the fruit fly Drosophila melanogaster as an experimental system or wish to understand Drosophila biological knowledge in relation to human disease or to other model systems, FlyBase can help you successfully find the information you are looking for. Here, we demonstrate some of our more advanced searching systems and highlight some of our new tools for searching the wealth of data on FlyBase. The first section explores gene function in FlyBase, using our TermLink tool to search with Controlled Vocabulary terms and our new RNA-Seq Search tool to search gene expression. The second section of this article describes a few ways to search genomic data in FlyBase, using our BLAST server and the new implementation of GBrowse 2, as well as our new FeatureMapper tool. Finally, we move on to discuss our most powerful search tool, QueryBuilder, before describing pre-computed cuts of the data and how to query the database programmatically.

tagtog: interactive and text-mining-assisted annotation of gene mentions in PLOS full-text articles.

The breadth and depth of biomedical literature are increasing year upon year. To keep abreast of these increases, FlyBase, a database for Drosophila genomic and genetic information, is constantly exploring new ways to mine the published literature to increase the efficiency and accuracy of manual curation and to automate some aspects, such as triaging and entity extraction. Toward this end, we present the 'tagtog' system, a web-based annotation framework that can be used to mark up biological entities (such as genes) and concepts (such as Gene Ontology terms) in full-text articles. tagtog leverages manual user annotation in combination with automatic machine-learned annotation to provide accurate identification of gene symbols and gene names. As part of the BioCreative IV Interactive Annotation Task, FlyBase has used tagtog to identify and extract mentions of Drosophila melanogaster gene symbols and names in full-text biomedical articles from the PLOS stable of journals. We show here the results of three experiments with different sized corpora and assess gene recognition performance and curation speed. We conclude that tagtog-named entity recognition improves with a larger corpus and that tagtog-assisted curation is quicker than manual curation. DATABASE URL: www.tagtog.net, www.flybase.org.

On the reproducibility of science: unique identification of research resources in the biomedical literature.

Scientific reproducibility has been at the forefront of many news stories and there exist numerous initiatives to help address this problem. We posit that a contributor is simply a lack of specificity that is required to enable adequate research reproducibility. In particular, the inability to uniquely identify research resources, such as antibodies and model organisms, makes it difficult or impossible to reproduce experiments even where the science is otherwise sound. In order to better understand the magnitude of this problem, we designed an experiment to ascertain the "identifiability" of research resources in the biomedical literature. We evaluated recent journal articles in the fields of Neuroscience, Developmental Biology, Immunology, Cell and Molecular Biology and General Biology, selected randomly based on a diversity of impact factors for the journals, publishers, and experimental method reporting guidelines. We attempted to uniquely identify model organisms (mouse, rat, zebrafish, worm, fly and yeast), antibodies, knockdown reagents (morpholinos or RNAi), constructs, and cell lines. Specific criteria were developed to determine if a resource was uniquely identifiable, and included examining relevant repositories (such as model organism databases, and the Antibody Registry), as well as vendor sites. The results of this experiment show that 54% of resources are not uniquely identifiable in publications, regardless of domain, journal impact factor, or reporting requirements. For example, in many cases the organism strain in which the experiment was performed or antibody that was used could not be identified. Our results show that identifiability is a serious problem for reproducibility. Based on these results, we provide recommendations to authors, reviewers, journal editors, vendors, and publishers. Scientific efficiency and reproducibility depend upon a research-wide improvement of this substantial problem in science today.

The Drosophila phenotype ontology.

BACKGROUND: Phenotype ontologies are queryable classifications of phenotypes. They provide a widely-used means for annotating phenotypes in a form that is human-readable, programatically accessible and that can be used to group annotations in biologically meaningful ways. Accurate manual annotation requires clear textual definitions for terms. Accurate grouping and fruitful programatic usage require high-quality formal definitions that can be used to automate classification. The Drosophila phenotype ontology (DPO) has been used to annotate over 159,000 phenotypes in FlyBase to date, but until recently lacked textual or formal definitions. RESULTS: We have composed textual definitions for all DPO terms and formal definitions for 77% of them. Formal definitions reference terms from a range of widely-used ontologies including the Phenotype and Trait Ontology (PATO), the Gene Ontology (GO) and the Cell Ontology (CL). We also describe a generally applicable system, devised for the DPO, for recording and reasoning about the timing of death in populations. As a result of the new formalisations, 85% of classifications in the DPO are now inferred rather than asserted, with much of this classification leveraging the structure of the GO. This work has significantly improved the accuracy and completeness of classification and made further development of the DPO more sustainable. CONCLUSIONS: The DPO provides a set of well-defined terms for annotating Drosophila phenotypes and for grouping and querying the resulting annotation sets in biologically meaningful ways. Such queries have already resulted in successful function predictions from phenotype annotation. Moreover, such formalisations make extended queries possible, including cross-species queries via the external ontologies used in formal definitions. The DPO is openly available under an open source license in both OBO and OWL formats. There is good potential for it to be used more broadly by the Drosophila community, which may ultimately result in its extension to cover a broader range of phenotypes.