Searched "Drosophila" at DSHB antibody hybridoma bank? Try again!

Rumor has it DSHB has updated search rules such that a search with the term "Drosophila" that used to bring back about 100 results now retrieves more than 200. Happy antibody hunting!

Fly gene list resource live and published

The DRSC is pleased to say that our GLAD gene list annotation database is live at flyrnai.org/glad and published in the Journal of Genomics!

The tool lets you view curated gene lists, corresponding information, and more. Improvable through community input on genes to add, publications to check out, etc. relevant to specific litst.

Sneak peak for blog readers: Gene List Annotation for Drosophila (GLAD) at DRSC

For years the DRSC has been putting together gene lists, e.g. to build focused cell-based RNAi libraries like our kinases and phosphatases library.

We recently built an online tool, GLAD, to support search and view of the several gene lists put together by Hu et al. over the years. When possible, the lists are annotated with information regarding confidence. Some lists are based on biochemical function (e.g. kinases) and others are based on biological function (e.g. autophagy). Check it out! 

A companion paper has been accepted by Journal of Genomics. I'll post when it's out.

At the online tool, you can suggest additions or changes to the list, or suggest relevant papers, so that we can improve the resource over time.

We have also made it possible for the community to quickly use a gene list to find relevant TRiP and other RNAi fly stocks in public collections.

See also related post on the complementary gene groups resource at FlyBase.

New online resource for TALE design: SIFTED

The Bulyk lab at Brigham and Women's Hospital has launched the software suite SIFTED, which should be useful to folks designing or interpreting results using Tal Effector Nucleases (TALEs).

Corresponding publication: Rogers JM, Barrera LA, Reyon D, Sander JD, Kellis M, Keith Joung J, Bulyk ML. Context influences on TALE-DNA binding revealed by quantitative profiling. Nat Commun. 2015 Jun 11;6:7440. PMID: 26067805.

IMP integrative tool for functional genomics updated to 2.0 version

Wong AK, Krishnan A, Yao V, Tadych A, Troyanskaya OG. IMP 2.0: a multi-species functional genomics portal for integration, visualization and prediction of protein functions and networks. Nucleic Acids Res. 2015 May 12. PMID: 25969450.

From the abstract: "... IMP 2.0 integrates updated prior knowledge and data collections from the last three years in the seven supported organisms (Homo sapiens, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Danio rerio, Caenorhabditis elegans, and Saccharomyces cerevisiae) and extends function prediction coverage to include human disease. ... Additionally, IMP 2.0 implements a new flexible platform for experts to generate custom hypotheses about biological processes or diseases, making sophisticated data-driven methods easily accessible to researchers. IMP does not require any registration or installation and is freely available for use at http://imp.princeton.edu."

Using phylogenetic relationships to predict protein functions--Sadreyev et al. release PhyloGene

In the 'not RNAi (or CRISPR) but might be of interest to blog readers anyway' department:

Sadreyev IR, Ji F, Cohen E, Ruvkun G, Tabach Y. PhyloGene server for identification and visualization of co-evolving proteins using normalized phylogenetic profiles. Nucleic Acids Res. 2015 May 9. pii: gkv452. PMID: 25958392.

From the abstract: "... Analysis of the similarity in patterns of sequence conservation across a large set of eukaryotes can predict functional associations between different proteins, identify new pathway members and reveal the function of previously uncharacterized proteins. We used normalized phylogenetic profiling to predict protein function and identify new pathway members and disease genes. The phylogenetic profiles of tens of thousands conserved proteins in the human, mouse, Caenorhabditis elegans and Drosophila genomes can be queried on our new web server, PhyloGene. ..."

FlyBase announces "Gene Group Reports"

FlyBase's May release includes "Gene Group Reports" (see FlyBase release notes news). I was able to view a list of all gene groups by entering the wild card "*" at the Simple tab on the Quick Search link box on the FlyBase home page.

GenomeRNAi announces data release v.14

The DKFZ's GenomeRNAi recently announced that "The database now contains phenotype data from 217 human RNAi screens and 201 screens in D. melanogaster. The total number of gene-phenotype associations has increased to over 1,2 million." That's a lot of associations!

GenomeRNAi beta-testing a 'screen comparison tool'

I recently stumbled across this beta-test at GenomeRNAi of a screen comparison tool. Enter one or a list of genes and view, heat-map style, in what screens those genes were hits. They indicate they're interested to receive feedback. The default option is human genes but Drosophila also supported.

SignedPPI included in list of "Signaling Breakthroughs of the Year"

How cool is this? SignedPPI, which was developed by the Perrimon lab and DRSC, made it onto the Signaling Breakthroughs of the Year list at Science Signaling!

Here's the paper that describes SignedPPI (free in PubMed Central): Vinayagam A, Zirin J, Roesel C, Hu Y, Yilmazel B, Samsonova AA, Neumüller RA, Mohr SE, Perrimon N. Integrating protein-protein interaction networks with phenotypes reveals signs of interactions. Nat Methods. 2014 Jan;11(1):94-9. PMID: 24240319; PMCID: PMC3877743.

Thinking ahead--What could custom CRISPR engineered cell lines do for your research?

Open call to the Drosophila research community from the DRSC:

Since it was founded in 2003 by Prof. N. Perrimon, the Drosophila RNAi Screening Center (DRSC) has served as a technology transfer center, helping the Drosophila community-at-large gain access to leading-edge technologies such as genome-wide RNAi.

As readers of this blog are likely aware, we have been working to support technology transfer in many areas additional to RNAi, including in the area of CRISPR-Cas9 engineering. For example, we developed and made freely available a database of short guide RNAs, accompanying genome browser-based online user interface, and sgRNA efficiency prediction tool to help support sgRNA selection for CRISPR-Cas9 engineering in flies (see www.flyrnai.org/crispr2).

The DRSC will apply early next year (end of February 2015) for renewal of our NIH R01 grant funding, which makes it possible for us to provide all we do to the community.

One of the things we are beginning to do with community members, and would like to propose to expand and continue in the next funding cycle, is to build custom CRISPR-Cas9-modified cell lines. These can be of value for a wide range of studies, including but not limited to RNAi screens using custom engineered cells (e.g. knockout mutant cells for sensitized screens, endogenously tagged loci for reporter assays or to screen for disruption of sub-cellular localization).

In short, we need your help!

If custom engineered cells would help your research--i.e. if you can imagine turning to the DRSC to help support making and/or screening of specific custom lines for your research within the next, say, 1-3 years, and particularly if you're a US-based lab, we would appreciate if you'd please get in touch and be willing to write a letter of support for our renewal application. We are of course also interested to hear from folks who are planning to use our library resources for other types of screens in the next few years, and from others who are depending on continuity of online resources and/or research services at the DRSC. Ideas for additional tools or resources are also welcome.

Please contact, or have your PI contact, DRSC Director (and blog author) Dr. Stephanie Mohr.

Genome editing--design tools

On my desk to read today--another paper related to CRISPRs.

Montague TG, Cruz JM, Gagnon JA, Church GM, Valen E. CHOPCHOP: a CRISPR/Cas9 and TALEN web tool for genome editing. Nucleic Acids Res. 2014 Jul;42(Web Server issue):W401-7. PMID: 24861617.

This report describes the ChopChop suite of tools, which includes support for Drosophila sgRNA design.

The DRSC offers our CRISPR2 sgRNA design tool, which provides a genome-browse view and includes efficiency scores (or you can run any designs through a 'calculator').

Additional tools are listed at AddGene.

The DRSC offers support for sgRNA and donor construct building through the Genome Engineering Production Group.

Integer linear optimization approach to signaling network construction based on protein-protein interaction and RNAi data sets

Ozsoy OE, Can T. A divide and conquer approach for construction of large-scale signaling networks from PPI and RNAi data using linear programming. IEEE/ACM Trans Comput Biol Bioinform. 2013 Jul-Aug;10(4):869-83. PMID: 24334382.

From the abstract: "... In this paper, we propose an integer linear optimization (ILP) model for reconstruction of signaling networks from RNAi data and a reference network. ..."

Related approaches available as online tools at the DRSC include COMPLEAT and SignedPPI

GenomeRNAi at DKFZ announces version 13

Our colleagues at the DKFZ recently announced that they have launched version 13 of GenomeRNAi. Their news item on the release indicates that the database "now contains phenotype data from 194 human RNAi screens and 183 screens in D. melanogaster" and that the "number of gene-phenotype associations has increased to over 950,000." Check it out!

Review--Functional Genomics Resources

My co-authors and I are pleased to present this Genetics journal "toolbox" series review article.

Mohr SE, Hu Y, Kim K, Housden BE, Perrimon N. Resources for Functional Genomics Studies in Drosophila melanogaster. Genetics. PubMed PMID: 24653003.

Please note that the final published version is now available--complete with live links to the many websites and online software tools we refer to.

New CRISPR tools at DRSC--Find CRISPR2 and Efficiency Tool

Interested in CRISPRs in flies? Check out the new version of our Find CRISPRs tool, Find CRISPRs Version 2, and new Efficiency Predictor that assigns a score to a given short guide RNA sequence.

The DRSC offers CRISPR design help, CRISPR sgRNA construct production and donor construct production. You can view services and our low prices, as well as place requests, at the website of the new Genome Engineering Production Group at the DRSC at HMS. We can send custom-made constructs to you or directly to a commercial Drosophila injection company.

Large-scale in vivo RNAi screen for factors related to germline stem cells

Yan D, Neumüller RA, Buckner M, Ayers K, Li H, Hu Y, Yang-Zhou D, Pan L, Wang X, Kelley C, Vinayagam A, Binari R, Randklev S, Perkins LA, Xie T, Cooley L, Perrimon N. A regulatory network of Drosophila germline stem cell self-renewal. Dev Cell. 2014 Feb 24;28(4):459-73. PMID: 24576427.

From the abstract: "... To comprehensively identify components of these networks, we performed a large-scale RNAi screen in Drosophila female germline stem cells (GSCs) covering ∼25% of the genome. The screen identified 366 genes that affect GSC maintenance, differentiation, or other processes involved in oogenesis. Comparison of GSC regulators with neural stem cell self-renewal factors identifies common and cell-type-specific self-renewal genes. ..."

These authors deposited screen data into RSVP, the TRiP's RNAi Stock Validation and Phenotypes data repository. Additional data submissions welcome!  Check it out online here.

Methods paper on fly RNAi in cells and in vivo

Humbly offered by your blog author ...


Mohr SE. RNAi screening in Drosophila cells and in vivo. Methods. 2014 Feb 24. pii: S1046-2023(14)00062-0. PMID: 24576618.

DKFZ's GenomeRNAi releases v.12

The DKFZ's GenomeRNAi team recently announced release of a version 12 with new data sets and features. Check it out!

Drosophila CRISPR approaches--Cas9 in the germline

These two papers, one of which is co-authored by folks here at the DRSC, describe using germline expression of Cas9 for CRISPR genome engineering approaches.

Sebo ZL, Lee HB, Peng Y, Guo Y. A simplified and efficient germline-specific CRISPR/Cas9 system for Drosophila genomic engineering. Fly (Austin). 2013 Oct 18;8(1). PMID: 24141137.

Ren X, Sun J, Housden BE, Hu Y, Roesel C, Lin S, Liu LP, Yang Z, Mao D, Sun L, Wu Q, Ji JY, Xi J, Mohr SE, Xu J, Perrimon N, Ni JQ. Optimized gene editing technology for Drosophila melanogaster using germ line-specific Cas9. Proc Natl Acad Sci U S A. 2013 Nov 4. PMID: 24191015. Note: This paper includes a description of our searchable online resource of pre-computed CRISPR sgRNA designs.