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Featured Useful resource: FlyBase

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Doing nice science will depend on teamwork, whether or not that is inside the lab or in collaboration with different labs. Nevertheless, generally the assets that assist our work will be ignored. Our ‘Featured useful resource’ sequence goals to shine a light-weight on these unsung heroes of the science world. In our newest article, we hear from Vitor Trovisco (Curator at FlyBase) and others within the staff, who describe the work of FlyBase.

Overview

FlyBase (flybase.org) is the first knowledgebase and hub for genomic, genetic and useful information on the fruit fly, Drosophila melanogaster. FlyBase was established in 1992, following funding from the Nationwide Heart for Human Genome Analysis of the NIH, USA [Ashburner M, 1994; The FlyBase Consortium, 1994], as a web-based database for data on the fruit fly’s genes and mutations that had beforehand been collated within the Pink E book [Lindsley and Zimm, 1992], and has since accompanied the fixed advances in genomics and genetics. These days, FlyBase hosts a complete and ever-growing assortment of knowledge curated from giant scale tasks to main analysis publications, which embody gene fashions, expression patterns and performance, alleles and transgenic constructs, phenotypes, genetic and bodily interactions, illness fashions, gene teams, giant datasets, fly shares and different reagents. Moreover, FlyBase hosts many linkouts to exterior assets, significantly these from which it attracts information (e.g. UniProt, NCBI, FlyAtlas/2) and a number of other which offer reagents and superior analysis instruments for fly analysis (e.g., fly inventory centres, DNA clones, Drosophila RNAi Screening Heart). Discover a complete record of exterior assets right here.

Folks behind FlyBase

FlyBase is a world consortium of biocurators and IT builders primarily based at Harvard College (USA), Indiana College (USA), the College of New Mexico (USA) and the College of Cambridge (UK). Harvard hosts the IT builders answerable for the database infrastructure, and the staff of curators chargeable for genomic options, gene fashions, expression patterns, illness fashions and bodily interactions. Indiana hosts the IT builders entrusted with the web site and its question instruments. Cambridge hosts the staff of curators answerable for genetic entities, phenotypes and genetic interactions, useful information (GO), neuronal gene expression patterns (with VFB), single cell expression information, and ontologies. The staff at New Mexico contributes to basic curation and bodily interactions curation. For the complete staff, see right here

FlyBase additionally enjoys nice assist from its exterior scientific advisory board, which incorporates Drosophila researchers and representatives of different genomic databases.

Collaborations

Alliance

FlyBase is a part of the Alliance of Genome Sources consortium (the Alliance), along with 5 different mannequin organism genomics databases (Saccharomyces Genome Database, WormBase, Mouse Genome Database, the Zebrafish Info Community, Rat Genome Database) and the Gene Ontology Useful resource [Alliance of Genome Resources Consortium, 2022]. The Alliance goals to supply higher comparative biology information and instruments, by bringing collectively, harmonising and leveraging cross-species genetics and genomics information. As a part of the Alliance, FlyBase contributes to and advantages from this improved integration to the benefit of the broader biomedical subject.

Digital Fly Mind

FlyBase is carefully intertwined with Digital Fly Mind (VFB), an interactive web-based device for neurobiologists. VFB facilitates the research of detailed neuroanatomy, neuron connectivity and expression information of Drosophila melanogaster. VFB goals to make it simpler for researchers to seek out related anatomical data and reagents. VFB is a UK-based collaboration between the College of Edinburgh, the College of Cambridge/FlyBase, the MRC Laboratory of Molecular Biology and the EMBL-EBI. FlyBase collaborates within the curation of anatomical entities and transgene expression patterns and offers the transgene expression curation displayed by VFB. Within the close to future VFB may even present gene expression summaries derived from single cell information.

Single Cell Expression Atlas

The EMBL-EBI’s Single Cell Expression Atlas initiative re-analyses and standardises publicly-available single cell RNA sequencing research to make them extra comparable and simpler to interpret. By its browser, customers can simply visualise clusters of cells, their annotations, and seek for gene expression patterns. Our collaboration has expedited the curation of fly datasets and their integration into FlyBase, by dataset report pages and cell sort scRNAseq expression abstract ribbons on the gene report pages. This work is carefully coordinated with Digital Fly Mind.

Funding

Since inception, FlyBase has had the extraordinary monetary assist of the Nationwide Human Genome Analysis Institute on the U.S. Nationwide Institutes of Well being (NHGRI/NIH, at the moment U41HG000739), within the type of pluri-annual grants that guarantee FlyBase’s core operations: continuous curation of printed literature, upkeep and enchancment of each the database infrastructure and web site. FlyBase has additionally benefited from grants from different sources to combine particular new information sorts. At present these come from the US’s Nationwide Science Basis (DBI-2035515, 2039324), the UK’s Wellcome Belief (PLM13398) and the UK’s Biotechnology and Organic Sciences Analysis Council (BBSRC, BB/T014008). Moreover, the UK’s Medical Analysis Council has offered ongoing funding for gene operate annotation since 1996 (at the moment MR/N030117/1). Regardless of its continuous assist, NHGRI/NIH has needed to impose vital funding cuts in recent times, placing FlyBase and different mannequin organism genomic databases below some monetary pressure [Bellen, 2021]. Within the face of this and so as to proceed offering a excessive customary of service, FlyBase has needed to resort to crowd-funding from the Drosophila analysis group within the type of annual consumer charges. Researchers world wide have been extraordinarily beneficiant and their contributions have lessened the affect of the cuts. 

Useful resource overview and highlights

Most information in FlyBase is organised right into a sequence of report pages, equivalent to completely different information courses (e.g. gene, allele, aberration, dataset), every internet hosting various kinds of data. For instance, the report web page for a given gene shows its related phenotypes, expression patterns, illness fashions, and useful information (GO) amongst different information. Every sort of knowledge is organised as annotation entries, continuously in desk format. 

Knowledge can be found at completely different scales to cater to every kind of customers, from the occasional consumer to the ability consumer – see [Larkin, 2021; Gramates, 2022]. For probably the most frequent piecemeal use case, the ‘Fast search’ and ‘Bounce-to-gene'(J2G) instruments permit discovering and navigating to particular person report pages (see determine). For greater stage data-mining there’s an array of question instruments to discover, corresponding to Batch Obtain, QueryBuilder, CytoSearch and Characteristic Mapper (hyperlinks below ‘Instruments’ within the navigation bar). Energy customers can discover an array of APIs, obtain precomputed information with the complete dataset of a number of courses of knowledge, and even pay money for the entire database (hyperlinks below ‘Downloads’ within the navigation bar). Beneath are a couple of latest additions.

Interactive HitLists

Most FlyBase instruments retrieve their outcomes as Interactive HitLists, or can convert them into HitLists through an “Export to HitList” possibility, which permit customers to view, analyse and export outcomes (see determine). For instance, outcomes will be filtered by species or information sort. Choosing a single information class permits conversion between related information sorts (e.g. genes to alleles) and analysing outcomes by sort (e.g. aberrations by mutagen sort). Processed outcomes can then be exported as a downloaded file, as a brand new HitList, or to different instruments.

‘Gene teams and pathways’ report pages

These latest additions to FlyBase current units of associated genes, related by their membership to the identical signalling pathway (Pathway stories) or macromolecular complicated, or by sharing a standard molecular operate or organic position (Gene Teams)(see determine). The meeting of those gene units relies on their underlying GO annotations, which had been systematically reviewed from a variety of sources to make sure accuracy and findability. Gene teams are hierarchical. For instance, the “ENZYMES” gene group hosts the “OXIDOREDUCTASES”, “TRANSFERASES”, “HYDROLASES”, “LYASES”, “ISOMERASES”, “LIGASES” and “TRANSLOCASES” youngster teams, and every of those have their very own youngster teams. Pathway members are organised into “core” members, “optimistic regulators”, “adverse regulators” and “ligand manufacturing” members. Gene group and pathway report pages additionally show GO ribbon stacks, which permit for a fast visible comparability of the group members’ operate (see determine).

Experimental instruments

‘Experimental device’ information was launched to assist customers discover alleles and transgenes with explicit traits. We outline experimental instruments as generally used sequences with helpful properties which might be exploited to review the organic operate of one other gene product or a organic course of. Examples of various kinds of experimental device embody those who allow a gene product to be detected (e.g. the FLAG tag, EGFP, mCherry), goal a gene product someplace particular inside a cell (e.g. mitochondrial concentrating on sequence), drive expression in a binary system (e.g. UAS, GAL4) or are used to change mobile exercise (e.g. to inhibit/activate neurons). As new alleles and transgenes are added to the database, they’re additionally linked to any related experimental instruments, build up an image of what they’re manufactured from. This enables customers to simply browse and seek for fly shares with explicit properties (e.g. all EGFP-tagged transgenes of their gene of curiosity).

Consumer assist

FlyBase is rooted within the collaborative spirit of the Drosophila analysis group and good communication is essential to proceed offering a excessive customary of service. For that, FlyBase sends a few surveys a yr to the FlyBase Neighborhood Advisory Group, which is made up of volunteer customers at any profession stage, from any biology subject, and at any stage of experience on the database assets. Anybody can be a part of by following the hyperlink below ‘Neighborhood’ within the navigation bar. The surveys attempt to gauge the extent of utilization and satisfaction of sure instruments and what options might be added or eradicated, and are used to tell the main target of FlyBase useful resource improvement.

The question instruments and information show are designed to be intuitive, supported by clear assist pages. Video tutorials and ‘Tweetorials’ can be found for a lot of instruments and assets, significantly if new, revamped or closely used (see full record right here).

For extra direct interactions with the group, FlyBase tries to be current at main worldwide conferences, such because the US Annual Drosophila Analysis Convention and the European Drosophila Analysis Convention. And FlyBase all the time welcomes ideas, enquiries and corrections through our 

Helpmail (hyperlink on the backside of each web page). These messages are learn by everybody within the staff, in order that they are often addressed by probably the most appropriate individuals.

Assist from customers

The fly analysis group has all the time been extraordinarily supportive and might proceed to take action at many ranges. Along with the monetary assist talked about above, it’s extremely essential and appreciated if customers cite FlyBase at any time when doable in articles, displays and funding purposes (quotation hyperlink on the backside of each webpage). These acknowledgements make FlyBase’s affect on analysis extra tangible and particularly the article citations present metrics that can be utilized for funding purposes.

‘Gene snapshot’ summaries

FlyBase welcomes skilled researchers to contribute ’Gene Snapshot’ summaries for his or her favorite genes. These present a fast overview of the operate of a gene’s product, primarily based on key factors solicited by FlyBase, and are reviewed by curators.

Assist from authors 

Authors can even contribute in a number of methods to simplify the curation of their articles, finally permitting their information to be extra rapidly out there on the web site. 

If you write your paper…

Clear, detailed and correct descriptions of the experiments and assets minimises the curation effort and reduces the necessity to contact the authors. Articles ought to point out official FlyBase identifiers and nomenclature for entities corresponding to genes, alleles, shares and anatomical constructions and may specify the molecular particulars of newly created alleles. 

As soon as your paper is printed…

When a analysis or assessment paper is printed, authors ought to get an e-mail from FlyBase asking for his or her assist by filling within the Quick-Monitor Your Paper (FTYP) kind. It requests authors so as to add the genes their articles give attention to, which is able to develop into able to show the following launch, and minimal data on the sorts of experiments carried out, which triages and helps prioritise the article for additional curation.

Often FlyBase has to ship emails with clarification requests. Replying to those queries is significantly appreciated, because it permits for a extra full and correct seize of the printed information and makes it extra available for show. 

Bibliography

Alliance of Genome Sources Consortium. Harmonizing mannequin organism information within the Alliance of Genome Sources. Genetics. 2022 Apr 4;220(4):iyac022.

Ashburner M, Drysdale R. FlyBase–the Drosophila genetic database. Growth. 1994 Jul;120(7):2077-9.

Bellen HJ, Hubbard EJA, Lehmann R, Madhani HD, Solnica-Krezel L, Southard-Smith EM. Mannequin organism databases are in jeopardy. Growth. 2021 Oct 1;148(19):dev200193.

Gramates LS, Agapite J, Attrill H, Calvi BR, Crosby MA, Dos Santos G, Goodman JL, Goutte-Gattat D, Jenkins VK, Kaufman T, Larkin A, Matthews BB, Millburn G, Strelets VB. FlyBase: a guided tour of highlighted options. Genetics. 2022 Apr 4;220(4):iyac035.

Larkin A, Marygold SJ, Antonazzo G, Attrill H, Dos Santos G, Garapati PV, Goodman JL, Gramates LS, Millburn G, Strelets VB, Tabone CJ, Thurmond J; FlyBase Consortium. FlyBase: updates to the Drosophila melanogaster information base. Nucleic Acids Res. 2021 Jan 8;49(D1):D899-D907.

Lindsley, Zimm. The Genome of Drosophila melanogaster. Educational Press, 1992.

The FlyBase Consortium. FlyBase–the Drosophila database. Nucleic Acids Res. 1994 Sep;22(17):3456-8.

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