ALBERT

Description: Many coral reef fish form transient spawning aggregations at sites located a few to hundreds of kilometres from their normal residence areas. Reef fish spawning aggregations ("FSAs") are often heavily exploited, which make them targets for management with marine reserves. We used a per-recruit model to compare the long-term conservation (impacts on female spawning-stock biomass-per-recruit (SSBR) and female : male sex ratio, SR) and fisheries effects (impacts on yield-per-recruit, YPR) of spawning reserves vs. normal residence reserves for two data-poor populations from Seychelles with contrasting life history traits and sexual modes: the Siganus sutor population of the main granitic islands, which has a fast life history and is gonochoristic and the Epinephelus fuscoguttatus population of Farquhar Atoll, which has a slow life history and is protogynous. Overall, our results suggest that normal residence reserves are more effective at improving both the SSBR and YPR of S. sutor . In contrast, the protection of a substantial fraction of spawning sites is preferable for E. fuscoguttatus to ensure the reproductive output of this protogynous population through normalization of SR and maintenance of high SSBR. Neither spawning reserves nor normal residence reserves improved the YPR of E. fuscoguttatus . However, yields of E. fuscoguttatus may increase on the long term via recruitment subsidy if a substantial fraction of spawning sites is protected. This may occur only if the population was recruitment limited in the absence of reserves and increases in SSBR compensate for lost opportunities caused by the area closures. Sensitivity analyses revealed that the relative effects of spawning reserves and normal residence reserves relate more to the change in catchability occurring with FSA formation than to life history traits. Thus, normal residence reserves should be preferred over spawning reserves for S. sutor essentially because its catchability at spawning sites is low relative to many other aggregation-forming populations. S. sutor therefore suffers higher fishing mortality in normal residence areas than at FSA sites. Our study demonstrates that spawning reserves are not always the most effective tool for balancing conservation and exploitation objectives for FSA-forming populations, and that this measure should ideally be weighed against other management options.

Description: The Immuno Polymorphism Database (IPD) was developed to provide a centralized system for the study of polymorphism in genes of the immune system. Through the IPD project we have established a central platform for the curation and publication of locus-specific databases involved either directly or related to the function of the Major Histocompatibility Complex in a number of different species. We have collaborated with specialist groups or nomenclature committees that curate the individual sections before they are submitted to IPD for online publication. IPD consists of five core databases, with the IMGT/HLA Database as the primary database. Through the work of the various nomenclature committees, the HLA Informatics Group and in collaboration with the European Bioinformatics Institute we are able to provide public access to this data through the website http://www.ebi.ac.uk/ipd/ . The IPD project continues to develop with new tools being added to address scientific developments, such as Next Generation Sequencing, and to address user feedback and requests. Regular updates to the website ensure that new and confirmatory sequences are dispersed to the immunogenetics community, and the wider research and clinical communities.

Description: Motivation: Analysis of RNA sequencing (RNA-Seq) data revealed that the vast majority of human genes express multiple mRNA isoforms, produced by alternative pre-mRNA splicing and other mechanisms, and that most alternative isoforms vary in expression between human tissues. As RNA-Seq datasets grow in size, it remains challenging to visualize isoform expression across multiple samples. Results: To help address this problem, we present Sashimi plots, a quantitative visualization of aligned RNA-Seq reads that enables quantitative comparison of exon usage across samples or experimental conditions. Sashimi plots can be made using the Broad Integrated Genome Viewer or with a stand-alone command line program. Availability and implementation: Software code and documentation freely available here: http://miso.readthedocs.org/en/fastmiso/sashimi.html Contact: mesirov@broadinstitute.org , airoldi@fas.harvard.edu or cburge@mit.edu Supplementary information: Supplementary data are available at Bioinformatics online.

Description: : Although the 1000 Genomes haplotypes are the most commonly used reference panel for imputation, medical sequencing projects are generating large alternate sets of sequenced samples. Imputation in African Americans using 3384 haplotypes from the Exome Sequencing Project, compared with 2184 haplotypes from 1000 Genomes Project, increased effective sample size by 8.3–11.4% for coding variants with minor allele frequency 〈1%. No loss of imputation quality was observed using a panel built from phenotypic extremes. We recommend using haplotypes from Exome Sequencing Project alone or concatenation of the two panels over quality score-based post-imputation selection or IMPUTE2’s two-panel combination. Contact: yunli@med.unc.edu Supplementary information: Supplementary data are available at Bioinformatics online.

Description: The study of genetic influences on drug response and efficacy (‘pharmacogenetics’) has existed for over 50 years. Yet, we still lack a complete picture of how genetic variation, both common and rare, affects each individual's responses to medications. Exome sequencing is a promising alternative method for pharmacogenetic discovery as it provides information on both common and rare variation in large numbers of individuals. Using exome data from 2203 AA and 4300 Caucasian individuals through the NHLBI Exome Sequencing Project, we conducted a survey of coding variation within 12 Cytochrome P450 ( CYP ) genes that are collectively responsible for catalyzing nearly 75% of all known Phase I drug oxidation reactions. In addition to identifying many polymorphisms with known pharmacogenetic effects, we discovered over 730 novel nonsynonymous alleles across the 12 CYP genes of interest. These alleles include many with diverse functional effects such as premature stop codons, aberrant splicesites and mutations at conserved active site residues. Our analysis considering both novel, predicted functional alleles as well as known, actionable CYP alleles reveals that rare, deleterious variation contributes markedly to the overall burden of pharmacogenetic alleles within the populations considered, and that the contribution of rare variation to this burden is over three times greater in AA individuals as compared with Caucasians. While most of these impactful alleles are individually rare, 7.6–11.7% of individuals interrogated in the study carry at least one newly described potentially deleterious alleles in a major drug-metabolizing CYP .

Description: Many coral reef fish species form predictable, transient spawning aggregations. Many aggregations are overfished, making them a target for spatial management. Here, we develop a per-recruit model to evaluate the performance of no-take marine reserves protecting transient spawning aggregations. The model consists of only 14 demographic and exploitation-related parameters. We applied the model to a protogynous grouper and a gonochoristic rabbitfish from Seychelles and tested six scenarios regarding the extent of protected areas, the level of fish spawning-site fidelity, and fishing effort redistribution post reserve implementation. Spawning aggregation reserves improve spawning-stock biomass-per-recruit and reduce the sex ratio bias in protogynous populations for all scenarios examined. However, these benefits are often small and vary among the different scenarios and as a function of sexual ontogeny. In all scenarios, increases in yield-per-recruit do not occur or are negligible. The long-term yield increases due to spawning aggregation reserves may still occur, but only if spawning-stock biomass recovery results in a recruitment subsidy. Given these limited benefits, the value of no-take reserves must be weighed against those of other management options, such as fishing effort reduction and seasonal fishery closures. The latter is particularly appropriate when spawning and non-spawning areas overlap in space.

Description: There is a global trend in the depletion of transient reef fish spawning aggregations ("FSAs"), making them a primary target for management with marine protected areas (MPAs). Here, we review the observed and likely effectiveness of FSA MPAs, discuss how future studies could fill knowledge gaps, and provide recommendations for MPA design based on species' life history and behaviour, enforcement potential, and management goals. Modelling studies indicate that FSA MPAs can increase spawning-stock biomass and normalize sex ratio in protogynous fish populations, unless fishing mortality remains high outside protected FSA sites and spawning times. In the field, observations of no change or continued decline in spawning biomass are more common than population recovery. When empirical studies suggest that FSA MPAs may not benefit fish productivity or recovery, extenuating factors such as insufficient time since MPA creation, poor or lack of enforcement, inadequate design, and poorly defined management objectives are generally blamed rather than failure of the MPA concept. Results from both the empirical and modelling literature indicate that FSA MPAs may not improve exploitable biomass and fisheries yields; however, investigations are currently too limited to draw conclusions on this point. To implement effective FSA MPAs, additional modelling work, long-term monitoring programmes at FSA sites, and collections of fisheries-dependent data are required, with greater attention paid to the design and enforcement of area closures. We recommend a harmonized, adaptive approach that combines FSA MPA design with additional management measures to achieve explicitly stated objectives. Conservation objectives and, therefore, an overall reduction in mortality rates should be targeted first. Fisheries objectives build on conservation objectives, in that they require an overall reduction in mortality rates while maintaining sufficient access to exploitable biomass. Communication among researchers, regulatory agencies, park authorities, and fishers will be paramount for effective action, along with significant funds for implementation and enforcement.

Description: Data visualization is an essential component of genomic data analysis. However, the size and diversity of the data sets produced by today’s sequencing and array-based profiling methods present major challenges to visualization tools. The Integrative Genomics Viewer (IGV) is a high-performance viewer that efficiently handles large heterogeneous data sets, while providing a smooth and intuitive user experience at all levels of genome resolution. A key characteristic of IGV is its focus on the integrative nature of genomic studies, with support for both array-based and next-generation sequencing data, and the integration of clinical and phenotypic data. Although IGV is often used to view genomic data from public sources, its primary emphasis is to support researchers who wish to visualize and explore their own data sets or those from colleagues. To that end, IGV supports flexible loading of local and remote data sets, and is optimized to provide high-performance data visualization and exploration on standard desktop systems. IGV is freely available for download from http://www.broadinstitute.org/igv , under a GNU LGPL open-source license.

Description: Mammal species have made the transition to the marine environment several times, and their lineages represent one of the classical examples of convergent evolution in morphological and physiological traits. Nevertheless, the genetic mechanisms of their phenotypic transition are poorly understood, and investigations into convergence at the molecular level have been inconclusive. While past studies have searched for convergent changes at specific amino acid sites, we propose an alternative strategy to identify those genes that experienced convergent changes in their selective pressures, visible as changes in evolutionary rate specifically in the marine lineages. We present evidence of widespread convergence at the gene level by identifying parallel shifts in evolutionary rate during three independent episodes of mammalian adaptation to the marine environment. Hundreds of genes accelerated their evolutionary rates in all three marine mammal lineages during their transition to aquatic life. These marine-accelerated genes are highly enriched for pathways that control recognized functional adaptations in marine mammals, including muscle physiology, lipid-metabolism, sensory systems, and skin and connective tissue. The accelerations resulted from both adaptive evolution as seen in skin and lung genes, and loss of function as in gustatory and olfactory genes. In regard to sensory systems, this finding provides further evidence that reduced senses of taste and smell are ubiquitous in marine mammals. Our analysis demonstrates the feasibility of identifying genes underlying convergent organism-level characteristics on a genome-wide scale and without prior knowledge of adaptations, and provides a powerful approach for investigating the physiological functions of mammalian genes.

Description: The Immuno Polymorphism Database (IPD), http://www.ebi.ac.uk/ipd/ is a set of specialist databases related to the study of polymorphic genes in the immune system. The IPD project works with specialist groups or nomenclature committees who provide and curate individual sections before they are submitted to IPD for online publication. The IPD project stores all the data in a set of related databases. IPD currently consists of four databases: IPD-KIR, contains the allelic sequences of killer-cell immunoglobulin-like receptors, IPD-MHC, a database of sequences of the major histocompatibility complex of different species; IPD-HPA, alloantigens expressed only on platelets; and IPD-ESTDAB, which provides access to the European Searchable Tumour Cell-Line Database, a cell bank of immunologically characterized melanoma cell lines. The data is currently available online from the website and FTP directory. This article describes the latest updates and additional tools added to the IPD project.