The CATH domain structure database: new protocols and classification levels give a more comprehensive resource for exploring evolution

We report the latest release (version 3.0) of the CATH protein domain database (). There has been a 20% increase in the number of structural domains classified in CATH, up to 86 151 domains. Release 3.0 comprises 1110 fold groups and 2147 homologous superfamilies. To cope with the increases in diverse structural homologues being determined by the structural genomics initiatives, more sensitive methods have been developed for identifying boundaries in multi-domain proteins and for recognising homologues. The CATH classification update is now being driven by an integrated pipeline that links these automated procedures with validation steps, that have been made easier by the provision of information rich web pages summarising comparison scores and relevant links to external sites for each domain being classified. An analysis of the population of domains in the CATH hierarchy and several domain characteristics are presented for version 3.0. We also report an update of the CATH Dictionary of homologous structures (CATH-DHS) which now contains multiple structural alignments, consensus information and functional annotations for 1459 well populated superfamilies in CATH. CATH is directly linked to the Gene3D database which is a projection of CATH structural data onto ∼2 million sequences in completed genomes and UniProt

A high-resolution map of human evolutionary constraint using 29 mammals.

The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ∼4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ∼60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease

The Joint IOC (of UNESCO) and WMO collaborative effort for met-ocean services

The Joint Committee for Oceanography and Marine Meteorology (JCOMM), a joint technical commission of IOC of UNESCO and WMO, has devised a coordination mechanism for the fit-for-purpose delivery of an end-to-end system, from ocean observations to met-ocean operational services. This paper offers a complete overview of the activities carried out by JCOMM and the status of the achievements up to 2017. The JCOMM stakeholders are the WMO Members and the IOC Member States, their research and operational Institutions, which mandated JCOMM to devise an international strategy to advance toward the achievement of the United Nations Sustainable Development Goals. The three activity areas, namely the Observation Program Area-OPA, the Data Management Program Area-DMPA and the Services and Forecasting Services Program Area-SFSPA have established several expert teams to contribute to the international coordination. OPA is organized in observing networks connected with different observing technologies, DMPA organizes the overall near-real time and delayed mode data assembly and delivery methodology and architecture and the SFSPA coordinates the met-ocean services stemming out of observations and data management. The future developments should strengthen the coordination in the three program areas considering the inclusion of new and emergent observing technologies, the interoperability of met-ocean data assembly centers and the establishment of efficient research to operations protocols, as well as better fit-for-purpose customized services for the public and private sectors

A High-Resolution Map of Human Evolutionary Constraint Using 29 Mammals

The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ~4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ~60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease.National Human Genome Research Institute (U.S.)National Institute of General Medical Sciences (U.S.) (Grant number GM82901)National Science Foundation (U.S.). Postdoctural Fellowship (Award 0905968)National Science Foundation (U.S.). Career (0644282)National Institutes of Health (U.S.) (R01-HG004037)Alfred P. Sloan Foundation.Austrian Science Fund. Erwin Schrodinger Fellowshi

The Joint IOC (of UNESCO) and WMO collaborative effort for Met-Ocean services

The WMO-IOC Joint Technical Commission for Oceanography and Marine Meteorology (JCOMM) has devised a coordination mechanism for the fit-for-purpose delivery of an end-to-end system, from ocean observations to met-ocean operational services. This paper offers a complete overview of the activities carried out by JCOMM and the status of the achievements up to 2018. The JCOMM stakeholders consist of the research and operational institutions of WMO members and the IOC member states, which mandated JCOMM to devise an international strategy to move toward the achievement of the United Nations Sustainable Development Goals. The three areas of activity are the Observation Program Area (OPA), the Data Management Program Area (DMPA) and the Services and Forecasting Services Program Area (SFSPA), and several expert teams have been established to contribute to the international coordination efforts. OPA is organized into observing networks connected by different observing technologies, DMPA organizes the overall near-real time and delayed mode data assembly, and the delivery methodology and architecture, and the SFSPA coordinates the met-ocean services resulting from the observations and data management. Future developments should enhance coordination in these three program areas by considering the inclusion of new and emergent observing technologies, the interoperability of met-ocean data assembly centers and the establishment of efficient research to operations protocols, in addition to better fit-for-purpose customized services in both the public and private sectors

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The CATH hierarchy revisited - structural divergence in domain superfamilies and the continuity of fold space

This paper explores the structural continuum in CATH and the extent to which superfamilies adopt distinct folds. Although most superfamilies are structurally conserved, in some of the most highly populated superfamilies (4% of all superfamilies) there is considerable structural divergence. While relatives share a similar fold in the evolutionary conserved core, diverse elaborations to this core can result in significant differences in the global structures. Applying similar protocols to examine the extent to which structural overlaps occur between different fold groups, it appears this effect is confined to just a few architectures and is largely due to small, recurring super-secondary motifs (e.g., αβ-motifs, α-hairpins). Although 24% of superfamilies overlap with superfamilies having different folds, only 14% of nonredundant structures in CATH are involved in overlaps. Nevertheless, the existence of these overlaps suggests that, in some regions of structure space, the fold universe should be seen as more continuous

An Overview of Ensembl

Ensembl (http://www.ensembl.org/) is a bioinformatics project to organize biological information around the sequences of large genomes. It is a comprehensive source of stable automatic annotation of individual genomes, and of the synteny and orthology relationships between them. It is also a framework for integration of any biological data that can be mapped onto features derived from the genomic sequence. Ensembl is available as an interactive Web site, a set of flat files, and as a complete, portable open source software system for handling genomes. All data are provided without restriction, and code is freely available. Ensembl's aims are to continue to “widen” this biological integration to include other model organisms relevant to understanding human biology as they become available; to “deepen” this integration to provide an ever more seamless linkage between equivalent components in different species; and to provide further classification of functional elements in the genome that have been previously elusive