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      FlyBase at 25: looking to the future

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          Abstract

          Since 1992, FlyBase ( flybase.org) has been an essential online resource for the Drosophila research community. Concentrating on the most extensively studied species, Drosophila melanogaster, FlyBase includes information on genes (molecular and genetic), transgenic constructs, phenotypes, genetic and physical interactions, and reagents such as stocks and cDNAs. Access to data is provided through a number of tools, reports, and bulk-data downloads. Looking to the future, FlyBase is expanding its focus to serve a broader scientific community. In this update, we describe new features, datasets, reagent collections, and data presentations that address this goal, including enhanced orthology data, Human Disease Model Reports, protein domain search and visualization, concise gene summaries, a portal for external resources, video tutorials and the FlyBase Community Advisory Group.

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          Most cited references24

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          Identification of functional elements and regulatory circuits by Drosophila modENCODE.

          To gain insight into how genomic information is translated into cellular and developmental programs, the Drosophila model organism Encyclopedia of DNA Elements (modENCODE) project is comprehensively mapping transcripts, histone modifications, chromosomal proteins, transcription factors, replication proteins and intermediates, and nucleosome properties across a developmental time course and in multiple cell lines. We have generated more than 700 data sets and discovered protein-coding, noncoding, RNA regulatory, replication, and chromatin elements, more than tripling the annotated portion of the Drosophila genome. Correlated activity patterns of these elements reveal a functional regulatory network, which predicts putative new functions for genes, reveals stage- and tissue-specific regulators, and enables gene-expression prediction. Our results provide a foundation for directed experimental and computational studies in Drosophila and related species and also a model for systematic data integration toward comprehensive genomic and functional annotation.
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            Versatile P(acman) BAC Libraries for Transgenesis Studies in Drosophila melanogaster

            We constructed Drosophila melanogaster BAC libraries with 21-kb and 83-kb inserts in the P(acman) system. Clones representing 12-fold coverage and encompassing more than 95% of annotated genes were mapped onto the reference genome. These clones can be integrated into predetermined attP sites in the genome using ΦC31 integrase to rescue mutations. They can be modified through recombineering, for example to incorporate protein tags and assess expression patterns.
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              Genome-wide analysis of promoter architecture in Drosophila melanogaster.

              Core promoters are critical regions for gene regulation in higher eukaryotes. However, the boundaries of promoter regions, the relative rates of initiation at the transcription start sites (TSSs) distributed within them, and the functional significance of promoter architecture remain poorly understood. We produced a high-resolution map of promoters active in the Drosophila melanogaster embryo by integrating data from three independent and complementary methods: 21 million cap analysis of gene expression (CAGE) tags, 1.2 million RNA ligase mediated rapid amplification of cDNA ends (RLM-RACE) reads, and 50,000 cap-trapped expressed sequence tags (ESTs). We defined 12,454 promoters of 8037 genes. Our analysis indicates that, due to non-promoter-associated RNA background signal, previous studies have likely overestimated the number of promoter-associated CAGE clusters by fivefold. We show that TSS distributions form a complex continuum of shapes, and that promoters active in the embryo and adult have highly similar shapes in 95% of cases. This suggests that these distributions are generally determined by static elements such as local DNA sequence and are not modulated by dynamic signals such as histone modifications. Transcription factor binding motifs are differentially enriched as a function of promoter shape, and peaked promoter shape is correlated with both temporal and spatial regulation of gene expression. Our results contribute to the emerging view that core promoters are functionally diverse and control patterning of gene expression in Drosophila and mammals.
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                Author and article information

                Journal
                Nucleic Acids Res
                Nucleic Acids Res
                nar
                nar
                Nucleic Acids Research
                Oxford University Press
                0305-1048
                1362-4962
                04 January 2017
                30 October 2016
                30 October 2016
                : 45
                : Database issue , Database issue
                : D663-D671
                Affiliations
                [1 ]The Biological Laboratories, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA
                [2 ]Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK
                [3 ]Department of Biology, Indiana University, Bloomington, IN 47405, USA
                [4 ]Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
                Author notes
                [* ]To whom correspondence should be addressed. Tel: +1 617 495 9925; Fax: +1 617 495 1354; Email: sian@ 123456morgan.harvard.edu
                []The members of the FlyBase Consortium are listed in the Acknowledgments.
                Author information
                http://orcid.org/0000-0002-6700-3797
                Article
                10.1093/nar/gkw1016
                5210523
                27799470
                23705520-1a70-4b88-9142-6c3192820ea7
                © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@ 123456oup.com

                History
                : 18 October 2016
                : 14 October 2016
                : 30 September 2016
                Page count
                Pages: 9
                Categories
                Database Issue
                Custom metadata
                04 January 2017

                Genetics
                Genetics

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