Integrative Genomic Analysis by Interoperation Of

BRIEF COMMUNICATIONS format converters, relieving scientists of the burden of identi- Integrative genomic fying and scripting the conversions. The GenomeSpace Recipe Resource is a growing set of high-utility use cases that demon- analysis by interoperation strate how to leverage multiple tools and serve as quick guides to analysis tasks. The website serves as a knowledge base, newsstand of bioinformatics tools and point of contact and help for the community of users and tool developers. in GenomeSpace Initially seeded by a consortium of biology research labs and development teams of six popular bioinformatics tools Kun Qu1,12, Sara Garamszegi2,12, Felix Wu2,12, (Cytoscape1,2, Galaxy3, GenePattern4, Genomica5, the Integrative Helga Thorvaldsdottir2, Ted Liefeld2,3, Marco Ocana2,3, Genomics Viewer (IGV)6 and the UCSC Table Browser7), Diego Borges-Rivera4, Nathalie Pochet2,5, GenomeSpace now connects 20 tools and data resources. Our James T Robinson2,3, Barry Demchak3, Tim Hull3, consortium labs provided biological projects and analytical needs 6,7 8 9 to drive GenomeSpace design and development. For example, we Gil Ben-Artzi , Daniel Blankenberg , Galt P Barber , 8,9 9 9 8 recapitulated the steps and results of published analyses within Brian T Lee , Robert M Kuhn , Anton Nekrutenko , GenomeSpace (Supplementary Figs. 1 and 2), dissecting and 6 3 2,3 2,4,10 Eran Segal , Trey Ideker , Michael Reich , Aviv Regev , visualizing the gene regulatory networks in human cancer stem Howard Y Chang1,11 & Jill P Mesirov2,3 cells (Supplementary Note 1, Supplementary Figs. 2–5). The study required diverse data types, analytical steps and methods Complex biomedical analyses require the use of multiple and multiple data transfers between tools. While originally software tools in concert and remain challenging for much of requiring substantial scripting, this work can now be performed the biomedical research community. We introduce GenomeSpace by non-programming biologists using only the GenomeSpace (http://www.genomespace.org), a cloud-based, cooperative platform and tools within it. community resource that currently supports the streamlined From a user’s perspective (Fig. 1 and Supplementary Fig. 6), interaction of 20 bioinformatics tools and data resources. GenomeSpace has several features that together facilitate integra- To facilitate integrative analysis by non-programmers, Nature America, Inc. All rights reserved. America, Inc. Nature tive analysis with a low barrier to user entry: (i) the collection of 6 it offers a growing set of ‘recipes’, short workflows to guide resident tools spanning a broad range of applications (Table 1); investigators through high-utility analysis tasks. (ii) easy dataset management in a variety of cloud storage types, © 201 alongside data-sharing capabilities (all account holders receive The integrative analysis of diverse data types with multiple soft- an allocation of cloud storage, and GenomeSpace also supports ware tools remains an enormous challenge for many biologists. connections to other cloud accounts (Dropbox, Google Drive, npg There is an ever-growing gap between the need to use various Amazon S3)); (iii) the ability to launch tools and to move data analysis and visualization tools and the complications of getting and analyses between tools, all facilitated by ‘behind-the-scenes’ tools from different sources to work together. Moreover, it is dif- file format converters (each tool retains its native environment ficult—even for experts, but especially for less computationally and presents the same user interface and functionality as when oriented biologists—to keep up with all of the available tools and launched outside of GenomeSpace); and (iv) a lightweight, simple, to identify the right recipes to follow, particularly in the absence unifying web interface. In summary, from the web interface of an accepted ‘laboratory manual’ for analytic protocols. a researcher can launch a tool and simultaneously feed it input Here, we present GenomeSpace, an open-source interoperability data files, move analysis results into other tools as needed through platform and community resource to enable non-programming simple launching operations, and collect additional processed scientists to work easily across data types and analysis methods data within cloud accounts or local storage. (http://www.genomespace.org). GenomeSpace provides a ‘tool We developed the GenomeSpace Recipe Resource (http://www. launch pad’ into which tools can be seamlessly added, and a genomespace.org/recipes) to aid researchers in identifying the ‘data highway’ that handles transfers between tools through steps required to perform a genomic analysis—a challenging task 1Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California, USA. 2The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. 3Department of Medicine, University of California, San Diego, La Jolla, California, USA. 4Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. 5Program in Translational NeuroPsychiatric Genomics, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA. 6Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel. 7Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. 8Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, Pennsylvania, USA. 9UC Santa Cruz Genomics Institute, University of California, Santa Cruz, Santa Cruz, California, USA. 10Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. 11Howard Hughes Medical Institute, Stanford University, Stanford, California, USA. 12These authors contributed equally to this work. Correspondence should be addressed to J.P.M. ([email protected]). RECEIVED 15 APRIL 2015; ACCEPTED 4 DECEMBER 2015; PUBLISHED ONLINE 18 JANUarY 2016; DOI:10.1038/NMETH.3732 NATURE METHODS | VOL.13 NO.3 | MARCH 2016 | 245 BRIEF COMMUNICATIONS Tool Current recipes cover diverse genomic analyses as well as basic Dropbox Tool and data Data utilities for using GenomeSpace itself (Supplementary Table 1). connection and source transfer manager We are adding social media vehicles to make recipe collection a Tool crowdsourced, collaborative effort, and we encourage suggestions Google Drive Data for new multitool recipes and ideas to improve existing recipes. source An example from the Recipe Resource illustrates how to “Find Tool User interface subnetworks of differentially expressed genes and identify associ- Amazon S3 Data ated biological functions.” Briefly, given a gene expression dataset, source this recipe identifies network interactions between differentially expressed genes and annotates the biological functions within sub- Cloud-based storage GenomeSpace components Bioinformatics tools networks via the Gene Ontology (GO) (Supplementary Fig. 7). platforms for user data and data resources The example dataset provided with this recipe is gene expression Figure 1 | The GenomeSpace environment for interoperation of data from a study in which granulocyte-macrophage progenitor bioinformatics tools. cells were transformed into leukemia stem cells by the introduction of an oncogene, MLL-AF9 (ref. 11). Applying the recipe identifies processes that are correlated with transformation from a normal even for short analyses. Although preconstructed pipelines can to a leukemic phenotype (Supplementary Fig. 8), such as embody the entire workflow of a study, they may be insufficiently SMAD1-dependent signaling, a process associated with the reg- flexible for exploratory research. We took an alternative approach ulation of hematopoietic differentiation by TGF-β and BMP12. by providing a collection or ‘cookbook’ of recipes: i.e., compre- We also describe a second recipe example, “Identify biological hensive descriptions of cross-tool analysis workflows. Recipes are functions for genes in copy number variation (CNV) regions” generally short, involving two or three tools, but commoditize (Supplementary Note 2 and Supplementary Figs. 9 and 10). important research tasks that investigators can employ as part An important design goal was to facilitate rapid addition of more complex analyses. The notion of our Recipe Resource of diverse tools contributed by the developer community. is modeled after the classical lab guide Molecular Cloning: This provides mutual benefit by extending the capabilities of A Laboratory Manual10, which used a similar approach to democ- GenomeSpace while also giving independent developers’ tools ratize molecular biology three decades ago. simultaneous access to all GenomeSpace-connected tools and Each GenomeSpace recipe contains a motivating biological data sources, circumventing the need to connect to each one problem, a relevant example dataset, detailed recipe steps and one individually. Recent cross-tool interoperability efforts have used possible interpretation of the results. Recipes include screenshot one of several approaches: aggregators host a large number of guides and videos that help walk users through the workflow. command line tools (Galaxy, GenePattern); plug-in architectures Nature America, Inc. All rights reserved. America, Inc. Nature 6 Table 1 | GenomeSpace provides access to a diverse set of bioinformatics tools and resources Tool name Organization Project website © 201 Analysis and visualization tools Cistrome Dana-Farber Cancer Institute

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