Plant Reactome: a resource for plant pathways and comparative analysis

Plant Reactome (http://plantreactome.gramene.org/) is a free, open-source, curated plant pathway database portal, provided as part of the Gramene project. The database provides intuitive bioinformatics tools for the visualization, analysis and interpretation of pathway knowledge to support genome annotation, genome analysis, modeling, systems biology, basic research and education. Plant Reactome employs the structural framework of a plant cell to show metabolic, transport, genetic, developmental and signaling pathways. We manually curate molecular details of pathways in these domains for reference species Oryza sativa (rice) supported by published literature and annotation of well-characterized genes. Two hundred twenty-two rice pathways, 1025 reactions associated with 1173 proteins, 907 small molecules and 256 literature references have been curated to date. These reference annotations were used to project pathways for 62 model, crop and evolutionarily significant plant species based on gene homology. Database users can search and browse various components of the database, visualize curated baseline expression of pathway-associated genes provided by the Expression Atlas and upload and analyze their Omics datasets. The database also offers data access via Application Programming Interfaces (APIs) and in various standardized pathway formats, such as SBML and BioPAX

Demonstrating public value to funders and other stakeholders—the journey of ELIXIR, a virtual and distributed research infrastructure for life science data

Open Science is a founding principle of ELIXIR, a pan-European research infrastructure for life science data, with 21 Member countries plus the European Molecular Biology Laboratory. The mission of ELIXIR is to coordinate bioinformatics resources so that they form a single, integrated and pan-European infrastructure, which can be used freely by academic and private-sector researchers across the globe. As a recipient of public and charitable funding, ELIXIR must demonstrate its value, and the need to produce evidence in support of this is intensifying. Our practice-led journey towards demonstrating public value is articulated around five main challenges and, for each, we present our pragmatic approach for tackling it. We begin by showing how we are working towards demystifying what research infrastructures do. We then shed light on the sort of evidence our funders and other stakeholders are asking us for, how this evidence varies in nature and scope, and our tactics to satisfy them. We follow-on by providing our thoughts on possible barriers and solutions to embedding impact evaluation in our activities. Finally, we provide lessons learned, which we believe are sufficiently transferable and will be inspirational to other research infrastructures as they embark on their own journeys to demonstrate public value.publishedVersio

Gramene 2016: comparative plant genomics and pathway resources

Gramene (http://www.gramene.org) is an online resource for comparative functional genomics in crops and model plant species. Its two main frameworks are genomes (collaboration with Ensembl Plants) and pathways (The Plant Reactome and archival BioCyc databases). Since our last NAR update, the database website adopted a new Drupal management platform. The genomes section features 39 fully assembled reference genomes that are integrated using ontology-based annotation and comparative analyses, and accessed through both visual and programmatic interfaces. Additional community data, such as genetic variation, expression and methylation, are also mapped for a subset of genomes. The Plant Reactome pathway portal (http://plantreactome.gramene.org) provides a reference resource for analyzing plant metabolic and regulatory pathways. In addition to approximately 200 curated rice reference pathways, the portal hosts gene homology-based pathway projections for 33 plant species. Both the genome and pathway browsers interface with the EMBL-EBI's Expression Atlas to enable the projection of baseline and differential expression data from curated expression studies in plants. Gramene's archive website (http://archive.gramene.org) continues to provide previously reported resources on comparative maps, markers and QTL. To further aid our users, we have also introduced a live monthly educational webinar series and a Gramene YouTube channel carrying video tutorials

Gramene 2018: unifying comparative genomics and pathway resources for plant research

Gramene (http://www.gramene.org) is a knowledgebase for comparative functional analysis in major crops and model plant species. The current release, #54, includes over 1.7 million genes from 44 reference genomes, most of which were organized into 62,367 gene families through orthologous and paralogous gene classification, whole-genome alignments, and synteny. Additional gene annotations include ontology-based protein structure and function; genetic, epigenetic, and phenotypic diversity; and pathway associations. Gramene's Plant Reactome provides a knowledgebase of cellular-level plant pathway networks. Specifically, it uses curated rice reference pathways to derive pathway projections for an additional 66 species based on gene orthology, and facilitates display of gene expression, gene-gene interactions, and user-defined omics data in the context of these pathways. As a community portal, Gramene integrates best-of-class software and infrastructure components including the Ensembl genome browser, Reactome pathway browser, and Expression Atlas widgets, and undergoes periodic data and software upgrades. Via powerful, intuitive search interfaces, users can easily query across various portals and interactively analyze search results by clicking on diverse features such as genomic context, highly augmented gene trees, gene expression anatomograms, associated pathways, and external informatics resources. All data in Gramene are accessible through both visual and programmatic interfaces

Gene Expression Atlas update—a value-added database of microarray and sequencing-based functional genomics experiments

Gene Expression Atlas (http://www.ebi.ac.uk/gxa) is an added-value database providing information about gene expression in different cell types, organism parts, developmental stages, disease states, sample treatments and other biological/experimental conditions. The content of this database derives from curation, re-annotation and statistical analysis of selected data from the ArrayExpress Archive and the European Nucleotide Archive. A simple interface allows the user to query for differential gene expression either by gene names or attributes or by biological conditions, e.g. diseases, organism parts or cell types. Since our previous report we made 20 monthly releases and, as of Release 11.08 (August 2011), the database supports 19 species, which contains expression data measured for 19 014 biological conditions in 136 551 assays from 5598 independent studies

Differential requirements for Tousled-like kinases 1 and 2 in mammalian development

The regulation of chromatin structure is critical for a wide range of essential cellular processes. The Tousled-like kinases, TLK1 and TLK2, regulate ASF1, a histone H3/H4 chaperone, and likely other substrates, and their activity has been implicated in transcription, DNA replication, DNA repair, RNA interference, cell cycle progression, viral latency, chromosome segregation and mitosis. However, little is known about the functions of TLK activity in vivo or the relative functions of the highly similar TLK1 and TLK2 in any cell type. To begin to address this, we have generated Tlk1- and Tlk2-deficient mice. We found that while TLK1 was dispensable for murine viability, TLK2 loss led to late embryonic lethality because of placental failure. TLK2 was required for normal trophoblast differentiation and the phosphorylation of ASF1 was reduced in placentas lacking TLK2. Conditional bypass of the placental phenotype allowed the generation of apparently healthy Tlk2-deficient mice, while only the depletion of both TLK1 and TLK2 led to extensive genomic instability, indicating that both activities contribute to genome maintenance. Our data identifies a specific role for TLK2 in placental function during mammalian development and suggests that TLK1 and TLK2 have largely redundant roles in genome maintenance

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe