Rachael P. Huntley

IntAct—open source resource for molecular interaction data

IntAct is an open source database and software suite for modeling, storing and analyzing molecular interaction data. The data available in the database originates entirely from published literature and is manually annotated by expert biologists to a high level of detail, including experimental methods, conditions and interacting domains. The database features over 126 000 binary interactions extracted from over 2100 scientific publications and makes extensive use of controlled vocabularies. The web site provides tools allowing users to search, visualize and download data from the repository. IntAct supports and encourages local installations as well as direct data submission and curation collaborations. IntAct source code and data are freely available from .

The Gene Ontology project in 2008

The Gene Ontology (GO) project (http://www.geneontology.org/) provides a set of structured, controlled vocabularies for community use in annotating genes, gene products and sequences (also see http://www.sequenceontology.org/). The ontologies have been extended and refined for several biological areas, and improvements to the structure of the ontologies have been implemented. To improve the quantity and quality of gene product annotations available from its public repository, the GO Consortium has launched a focused effort to provide comprehensive and detailed annotation of orthologous genes across a number of ‘reference’ genomes, including human and several key model organisms. Software developments include two releases of the ontology-editing tool OBO-Edit, and improvements to the AmiGO browser interface.

The Plant Cell Cycle

Molecular controls of the plant cell cycle must integrate environmental signals within developmental contexts. Recent advances highlight the fundamental conservation of underlying cell cycle mechanisms between animals and plants, overlaid by a rich molecular and regulatory diversity that is specific to plant systems. Here we review plant cell cycle regulators and their control.

The GOA database in 2009—an integrated Gene Ontology Annotation resource

The Gene Ontology Annotation (GOA) project at the EBI (http://www.ebi.ac.uk/goa) provides high-quality electronic and manual associations (annotations) of Gene Ontology (GO) terms to UniProt Knowledgebase (UniProtKB) entries. Annotations created by the project are collated with annotations from external databases to provide an extensive, publicly available GO annotation resource. Currently covering over 160 000 taxa, with greater than 32 million annotations, GOA remains the largest and most comprehensive open-source contributor to the GO Consortium (GOC) project. Over the last five years, the group has augmented the number and coverage of their electronic pipelines and a number of new manual annotation projects and collaborations now further enhance this resource. A range of files facilitate the download of annotations for particular species, and GO term information and associated annotations can also be viewed and downloaded from the newly developed GOA QuickGO tool (http://www.ebi.ac.uk/QuickGO), which allows users to precisely tailor their annotation set.

QuickGO: a web-based tool for Gene Ontology searching

Summary: QuickGO is a web-based tool that allows easy browsing of the Gene Ontology (GO) and all associated electronic and manual GO annotations provided by the GO Consortium annotation groups QuickGO has been a popular GO browser for many years, but after a recent redevelopment it is now able to offer a greater range of facilities including bulk downloads of GO annotation data which can be extensively filtered by a range of different parameters and GO slim set generation. Availability and Implementation: QuickGO has implemented in JavaScript, Ajax and HTML, with all major browsers supported. It can be queried online at http://www.ebi.ac.uk/QuickGO. The software for QuickGO is freely available under the Apache 2 licence and can be downloaded from http://www.ebi.ac.uk/QuickGO/installation.html Contact: goa@ebi.ac.uk; dbinns@ebi.ac.uk

The UniProt-GO Annotation database in 2011

The GO annotation dataset provided by the UniProt Consortium (GOA: http://www.ebi.ac.uk/GOA) is a comprehensive set of evidenced-based associations between terms from the Gene Ontology resource and UniProtKB proteins. Currently supplying over 100 million annotations to 11 million proteins in more than 360 000 taxa, this resource has increased 2-fold over the last 2 years and has benefited from a wealth of checks to improve annotation correctness and consistency as well as now supplying a greater information content enabled by GO Consortium annotation format developments. Detailed, manual GO annotations obtained from the curation of peer-reviewed papers are directly contributed by all UniProt curators and supplemented with manual and electronic annotations from 36 model organism and domain-focused scientific resources. The inclusion of high-quality, automatic annotation predictions ensures the UniProt GO annotation dataset supplies functional information to a wide range of proteins, including those from poorly characterized, non-model organism species. UniProt GO annotations are freely available in a range of formats accessible by both file downloads and web-based views. In addition, the introduction of a new, normalized file format in 2010 has made for easier handling of the complete UniProt-GOA data set.

The GOA database: gene ontology annotation updates for 2015

The Gene Ontology Annotation (GOA) resource (http://www.ebi.ac.uk/GOA) provides evidence-based Gene Ontology (GO) annotations to proteins in the UniProt Knowledgebase (UniProtKB). Manual annotations provided by UniProt curators are supplemented by manual and automatic annotations from model organism databases and specialist annotation groups. GOA currently supplies 368 million GO annotations to almost 54 million proteins in more than 480 000 taxonomic groups. The resource now provides annotations to five times the number of proteins it did 4 years ago. As a member of the GO Consortium, we adhere to the most up-to-date Consortium-agreed annotation guidelines via the use of quality control checks that ensures that the GOA resource supplies high-quality functional information to proteins from a wide range of species. Annotations from GOA are freely available and are accessible through a powerful web browser as well as a variety of annotation file formats.

The maize retinoblastoma protein homologue ZmRb-1 is regulated during leaf development and displays conserved interactions with G1/S regulators and plant cyclin D (CycD) proteins

Recent discoveries of plant retinoblastoma (Rb) protein homologues and D-type cyclins suggest that control of the onset of cell division in plants may have stronger parallels with mammalian G1/S controls than with yeasts. In mammals, the Rb protein interacts specifically with D-type cyclins and regulates cell proliferation by binding and inhibiting E2F transcription factors. However, the developmental role of Rb in plants and its potential interaction with cell cycle regulators is unknown. We show that the maize Rb homologue ZmRb-1 is temporally and spatially regulated during maize leaf development. ZmRb-1 is highly expressed in differentiating cells, but almost undetectable in proliferating cells. In vitro, both ZmRb-1 and human Rb bind all classes of plant D-type cyclins with the involvement of a conserved N-terminal Leu-x-Cys-x-Glu (LxCxE) Rb-interaction motif. This binding is strongly reduced by mutation of the conserved Cys-470 of ZmRb-1. ZmRb-1 binds human and Drosophila E2F, and inhibits transcriptional activation of human E2F. We also show that ZmRb-1 is a good in vitro substrate for all human G1/S protein kinases. The functional conservation of proteins that control the G1/S transition in mammals and plants points to the existence of plant E2F homologues. We conclude that evolution of Rb and cyclin D proteins occurred after separation of the fungi from the higher eukaryotic lineage, but preceded the divergence of plant and animal kingdoms.

The Gene Ontology's Reference Genome Project: A Unified Framework for Functional Annotation across Species

The Gene Ontology (GO) is a collaborative effort that provides structured vocabularies for annotating the molecular function, biological role, and cellular location of gene products in a highly systematic way and in a species-neutral manner with the aim of unifying the representation of gene function across different organisms. Each contributing member of the GO Consortium independently associates GO terms to gene products from the organism(s) they are annotating. Here we introduce the Reference Genome project, which brings together those independent efforts into a unified framework based on the evolutionary relationships between genes in these different organisms. The Reference Genome project has two primary goals: to increase the depth and breadth of annotations for genes in each of the organisms in the project, and to create data sets and tools that enable other genome annotation efforts to infer GO annotations for homologous genes in their organisms. In addition, the project has several important incidental benefits, such as increasing annotation consistency across genome databases, and providing important improvements to the GOs logical structure and biological content.

D-type cyclins activate division in the root apex to promote seed germination in Arabidopsis

Seeds provide survival and dispersal capabilities by protecting the dormant mature plant embryo. Germination and resumption of development under favourable conditions requires the reinitiation of cell growth and division through poorly understood processes. Here we show that four phases of cell division activation during germination in Arabidopsis are related to external morphological changes. Cell division initiates in the root apical meristem (RAM) before root protrusion, followed by sequential activation of cell division in the cotyledons, shoot apical meristem (SAM), and secondary meristems. Major changes in transcript levels of >2,000 genes precede root emergence, including expression peaks of six D-type (CYCD) and two A-type cyclins. Two further CYCDs are activated later with the SAM. Early activated CYCDs play key roles in regulating the extent of cell division, because loss-of-function alleles of early CYCDs display reduced division activation and consequential delayed root emergence. Conversely, elevation of early CYCDs increases cell cycle activation in the RAM and promotes embryonic root (radicle) protrusion, whereas a later-acting CYCD does not. These phenotypes, together with their overlapping expression domains, support a cumulative action of a subset of CYCDs in cell cycle reactivation, rather than a complete functional redundancy. This analysis reveals a phenotype associated with loss-of-function of a plant cyclin and demonstrates that D-type cyclins regulate cell cycle reentry during meristem activation to promote successful germination and early seedling growth.