UniProt: A worldwide hub of protein knowledge

Networks have become a key approach to understanding systems of interacting objects, unifying the study of diverse phenomena including biological organisms and human society. One crucial step when studying the structure and dynamics of networks is to identify communities: groups of related nodes that correspond to functional subunits such as protein complexes or social spheres. Communities in networks often overlap such that nodes simultaneously belong to several groups. Meanwhile, many networks are known to possess hierarchical organization, where communities are recursively grouped into a hierarchical structure. However, the fact that many real networks have communities with pervasive overlap, where each and every node belongs to more than one group, has the consequence that a global hierarchy of nodes cannot capture the relationships between overlapping groups. Here we reinvent communities as groups of links rather than nodes and show that this unorthodox approach successfully reconciles the antagonistic organizing principles of overlapping communities and hierarchy. In contrast to the existing literature, which has entirely focused on grouping nodes, link communities naturally incorporate overlap while revealing hierarchical organization. We find relevant link communities in many networks, including major biological networks such as protein-protein interaction and metabolic networks, and show that a large social network contains hierarchically organized community structures spanning inner-city to regional scales while maintaining pervasive overlap. Our results imply that link communities are fundamental building blocks that reveal overlap and hierarchical organization in networks to be two aspects of the same phenomenon.

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Link communities reveal multiscale complexity in networks

Current yeast interactome network maps contain several hundred molecular complexes with limited and somewhat controversial representation of direct binary interactions. We carried out a comparative quality assessment of current yeast interactome data sets, demonstrating that high-throughput yeast two-hybrid (Y2H) screening provides high-quality binary interaction information. Because a large fraction of the yeast binary interactome remains to be mapped, we developed an empirically controlled mapping framework to produce a "second-generation" high-quality, high-throughput Y2H data set covering approximately 20% of all yeast binary interactions. Both Y2H and affinity purification followed by mass spectrometry (AP/MS) data are of equally high quality but of a fundamentally different and complementary nature, resulting in networks with different topological and biological properties. Compared to co-complex interactome models, this binary map is enriched for transient signaling interactions and intercomplex connections with a highly significant clustering between essential proteins. Rather than correlating with essentiality, protein connectivity correlates with genetic pleiotropy.

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High-Quality Binary Protein Interaction Map of the Yeast Interactome Network

The Integrated Microbial Genomes (IMG) system serves as a community resource for comparative analysis of publicly available genomes in a comprehensive integrated context. IMG integrates publicly available draft and complete genomes from all three domains of life with a large number of plasmids and viruses. IMG provides tools and viewers for analyzing and reviewing the annotations of genes and genomes in a comparative context. IMG's data content and analytical capabilities have been continuously extended through regular updates since its first release in March 2005. IMG is available at http://img.jgi.doe.gov. Companion IMG systems provide support for expert review of genome annotations (IMG/ER: http://img.jgi.doe.gov/er), teaching courses and training in microbial genome analysis (IMG/EDU: http://img.jgi.doe.gov/edu) and analysis of genomes related to the Human Microbiome Project (IMG/HMP: http://www.hmpdacc-resources.org/img_hmp).

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IMG: the integrated microbial genomes database and comparative analysis system

Molecular Maps of the Reorganization of Genome-Nuclear Lamina Interactions during Differentiation

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.

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Trudy Torto Alalibo

Papers

The Gene Ontology project in 2008