Unique Identifcation of research resources in studies in Reproducibility Project: Cancer Biology

<p>Reproducibility Project: Cancer Biology (https://osf.io/e81xl/wiki/home/) aims to reproduce the key experiments from 50 landmark papers in cancer research. As a follow up to the previously published study, which showed a lack of indentifiability of research resources in the published biomedical literature (Vasilevsky, et al. 2014, PeerJ 1:e148), we analyzed 6 resource types reported in these papers to determine the identifiability of these resources. The resource types included antibodies, cell lines, constructs, knockdown reagents, model organisms and software. The results showed an average 85% of the resources were identifiable, and the ability to identify the resources varied amongst the resource types.</p

Unique Identification of research resources in studies in Reproducibility Project: Cancer Biology

<p>Reproducibility Project: Cancer Biology (https://osf.io/e81xl/wiki/home/) aims to reproduce the key experiments from 50 landmark papers in cancer research. As a follow up to the previously published study, which showed a lack of indentifiability of research resources in the published biomedical literature (Vasilevsky, et al. 2014, PeerJ 1:e148), we analyzed 6 resource types reported in these papers to determine the identifiability of these resources. The resource types included antibodies, cell lines, constructs, knockdown reagents, model organisms and software. The results showed an average 85% of the resources were identifiable, and the ability to identify the resources varied amongst the resource types.</p> <p> </p

Analyzed Results with statistics and figures

<p>Analyzed results from the Unique ID project. </p

Curation spreadsheets for all resource types.

<p>The original curation spreadsheets and data collected for the Unique ID project.</p

The BioSharing Registry: mapping the landscape of standards and databases resources in the life sciences

<p>BioSharing (http://www.biosharing.org) is a curated, web-based, searchable portal of three linked registries of content standards, databases and data policies in the life sciences, broadly encompassing the biological, natural and biomedical sciences. Our records are informative and discoverable, maximizing standards adoption and (re)use (e.g. in data policies), and allowing the monitoring of their maturity and evolution (Tenenbaum, Sansone, Haendel; Am Med Inform Assoc, 2014).</p> <p>With over 1,300 records, BioSharing content can be searched using simple or advanced searches, filtered via a filtering matrix, or grouped via the ‘Collection’ feature, according to field of interest or focus. Examples are the NPG Scientific Data and BioMedCentral Collections, collating and linking the recommended standards and repositories from their Data Policy for author. Similarly other publishers, projects and organizations are creating Collections by selecting and filtering standards and databases relevant to their work, such as the BD2K bioCADDIE project. As a community effort, BioSharing offers users the ability to ‘claim’ records, allowing their update. Each claimant also has a user profile that can be linked to their resources, publications and ORCID ID, thus providing visibility for them as an individual.<br>Launched in 2011 as an extension and evolution of the MIBBI portal (founded by the same Operational Team, led by Sansone), BioSharing is working with a growing number of journals and other registries; it is also part of ELIXIR-UK Node and contributing to the NIH BD2K CEDAR. Driven by an international Advisory Board (co-chaired by Tenenbaum, Haendel) the BioSharing userbase has grown by 40% over the last year, thanks to successful engagement with researchers, publishers, librarians, developers and other stakeholders via several routes, including a joint RDA/Force11 working group (co-chaired by Lawrence and Hodson) and a collaboration with the International Biocuration Society.</p> <p> </p

How to discover branching phenotypes?

<p>(Bottom panel) Phenotype data exhibiting various forms of branchiness are not easily discerned from diverse natural language descriptions. (A) Bee hairs are different from most other insect hairs in that they are plumose, which facilitates pollen collection. (B) A mutant of <i>Drosophila melanogaster</i> exhibits forked bristles, due to a variation in <i>mical</i>. (C) In zebrafish larvae (<i>Danio rerio</i>), angiogenesis begins with vessels branching. (D) Plant trichomes take on many forms, including trifurcation. (Top) Phenotypes involving some type of “branched” are easily recovered when they are represented with ontologies. In a semantic graph, free text descriptions are converted into phenotype statements involving an anatomy term from animal or plant ontologies <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002033#pbio.1002033-Haendel1" target="_blank">[56]</a>,<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002033#pbio.1002033-Cooper1" target="_blank">[118]</a> and a quality term from a quality ontology <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002033#pbio.1002033-Gkoutos1" target="_blank">[106]</a>, connected by a logical expression (“inheres_in some”). Anatomy (purple) and quality (green) terms (ontology IDs beneath) relate phenotype statements from different species by virtue of the logic inherent in the ontologies, e.g., plumose, bifurcated, branched, and tripartite are all subtypes of “branched.” Image credits: bumble bee with pollen by Thomas Bresson, seta with pollen by István Mikó, <i>Arabidopsis</i> plants with hair-like structures (trichomes) by Annkatrin Rose, <i>Drosophila</i> photo by John Tann, <i>Drosophila</i> bristles redrawn from <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002033#pbio.1002033-Hung1" target="_blank">[119]</a>, scanning electron micrograph of <i>Arabidopsis</i> trichome by István Mikó, zebrafish embryos by MichianaSTEM, zebrafish blood vessels from <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002033#pbio.1002033-Alvarez1" target="_blank">[120]</a>. Figure assembled by Anya Broverman-Wray.</p

Phenotypes shared across biology.

<p>Phenotype data are relevant to many different domains, but they are currently isolated in data “silos.” Research from a broad array of seemingly disconnected domains, as outlined here, can be dramatically accelerated with a computable data store. (<b>A</b>) <b>Domains</b>: Diverse fields such as evolutionary biology, human disease and medicine, and climate change relate to phenotypes. (<b>B</b>) <b>Phenotypes</b>: insects, vertebrates, plants, and even forests all have features that are branched in some way, but they are described using different terms. For a computer to discover this, the phenotypes must be annotated with unique identifiers from ontologies that are logically linked. Under “shape” in the PATO quality ontology <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002033#pbio.1002033-Gkoutos1" target="_blank">[106]</a>, “branchiness” is an encompassing parent term with subtypes “branched” and “increased branchiness.” From left to right, top layer, insects, vertebrates and plants have species that demonstrate phenotypes for which the genetic basis is not known. Often their companion model species, however, have experimental genetic work that is relevant to proposing candidate genes and gene networks. Insects (1): An evolutionary novelty in bees (top layer) is the presence of branched setae used for pollen collection. Nothing is known about the genetic basis of this feature. One clue to the origin of this evolutionary feature comes from studies of <i>Drosophila</i> (bottom layer), where <i>Mical</i> overexpression in unbranched wild-type bristles generates a branched morphology <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002033#pbio.1002033-Hung1" target="_blank">[119]</a>. Mical directly links semaphorins and their plexin receptors to the precise control of actin filament dynamics <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002033#pbio.1002033-Hung1" target="_blank">[119]</a>. Vertebrates (2): In humans, aberrant angiogenesis, including excessive blood vessel branching (top layer), is one of the six central hallmarks of cancer <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002033#pbio.1002033-Hanahan1" target="_blank">[121]</a>. Candidate genes have been identified using data from model organisms. In zebrafish (middle layer), studies of the control of sprouting in blood vessel development show that signaling via semaphorins <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002033#pbio.1002033-Yazdani1" target="_blank">[122]</a> and their plexin receptors is required for proper abundance and distribution <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002033#pbio.1002033-Gu1" target="_blank">[123]</a>; disruption of <i>plxnd1</i> results in increased branching <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002033#pbio.1002033-Alvarez1" target="_blank">[120]</a>,<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002033#pbio.1002033-Zygmunt1" target="_blank">[124]</a>,<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002033#pbio.1002033-TorresVazquez1" target="_blank">[125]</a>. In mouse (bottom layer), branching of salivary glands is dependent on semaphorin signaling <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002033#pbio.1002033-Chung1" target="_blank">[126]</a>, as is the branching of various other epithelial organs <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002033#pbio.1002033-Korostylev1" target="_blank">[127]</a>. Plants (3): The uppermost canopy of trees of the rainforest (top layer) undergo a marked increase in branching associated with climate change <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002033#pbio.1002033-Niinemets1" target="_blank">[128]</a>. Nothing is known about the genetic basis of this feature. The branching of plant trichomes (bottom layer), tiny outgrowths with a variety of functions including seed dispersal, has been studied in the model <i>Arabidopsis thaliana.</i> Branching occurs in association with many MYB-domain genes <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002033#pbio.1002033-Serna1" target="_blank">[129]</a>, transcription factors that are found in both plants and animals <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002033#pbio.1002033-Rosinski1" target="_blank">[130]</a>. (<b>C</b>) <b>Environment</b>: Diverse input from the environment influences organismal phenotype. (<b>D</b>) <b>Genes</b>: At the genetic level, previously unknown associations with various types of “branchiness” between insects and vertebrates are here made to possibly a common core or network of genes (the semaphorin-plexin signaling network). No association between genes associated with plant branching (Myb transcription factors) and animal branching is obvious from the literature. Image credit: Anya Broverman-Wray.</p

Finding phenotypes.

<p>The rich legacy of research in the life sciences includes a wealth of phenotype data contained in many sources, for millions of extinct and extant species. Some important sources of phenotypes date from more than 250 years ago <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002033#pbio.1002033-AristotleBalme1" target="_blank">[74]</a>–<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002033#pbio.1002033-Darwin1" target="_blank">[77]</a>. With very few exceptions, phenotype data are not computationally accessible <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002033#pbio.1002033-Ramrez2" target="_blank">[78]</a>.</p><p>Finding phenotypes.</p