{"id":352,"date":"2021-06-01T15:53:00","date_gmt":"2021-06-01T15:53:00","guid":{"rendered":"https:\/\/terrabioappdev.wpenginepowered.com\/panoply-framework-for-cancer-proteogenomics\/"},"modified":"2023-12-27T04:54:45","modified_gmt":"2023-12-27T04:54:45","slug":"panoply-framework-for-cancer-proteogenomics","status":"publish","type":"post","link":"https:\/\/terra.bio\/panoply-framework-for-cancer-proteogenomics\/","title":{"rendered":"Spotlight on PANOPLY, a scalable framework for cancer proteogenomics"},"content":{"rendered":"<p><i><span style=\"font-weight: 400;\">PANOPLY is an innovative computational framework for applying state-of-the-art statistical and machine learning algorithms to transform multi-omic data from cancer samples into biologically meaningful and interpretable results. In this guest blog post, D. R. Mani, principal computational scientist in the Broad Institute&#8217;s Proteomics Platform and lead author of the recently published <\/span><\/i><a href=\"https:\/\/www.nature.com\/articles\/s41592-021-01176-6\"><i><span style=\"font-weight: 400;\">PANOPLY paper<\/span><\/i><\/a><i><span style=\"font-weight: 400;\">, explains how his team is leveraging Terra to make PANOPLY accessible to a wide range of researchers.\u00a0\u00a0\u00a0<\/span><\/i><\/p>\n<p>&nbsp;<\/p>\n<hr \/>\n<p>&nbsp;<\/p>\n<p><span style=\"font-weight: 400;\">Proteogenomics involves the integrative analysis of genomic, transcriptomic, proteomic and post-translational modification (PTM) data produced by next-generation sequencing and mass spectrometry-based proteomics. Effectively analyzing proteogenomics data involves deploying complex computational algorithms that integrate multiple omics data types, and unfortunately, such algorithms remain largely inaccessible to non-computational cancer researchers. We decided to address this problem by building a framework called PANOPLY that would streamline analysis of proteogenomics data and would be easy to use, robust, flexible and reproducible. We wanted researchers to be able to use it on any standard computational platform, so we designed PANOPLY to be modular and portable, but we chose to also make it available through Terra to increase access, scalability and ease of use.<\/span><\/p>\n<p>&nbsp;<\/p>\n<h3><span style=\"font-weight: 400;\">A &#8220;greatest hits&#8221; compilation of methods from flagship CPTAC studies<\/span><\/h3>\n<p><span style=\"font-weight: 400;\">PANOPLY was not born in a vacuum. Proteogenomic analysis has been extensively applied to cancer samples in many studies published under the auspices of the <\/span><a href=\"https:\/\/proteomics.cancer.gov\/programs\/cptac\"><span style=\"font-weight: 400;\">Clinical Proteomic Tumor Analysis Consortium<\/span><\/a><span style=\"font-weight: 400;\"> (CPTAC) and the <\/span><a href=\"https:\/\/proteomics.cancer.gov\/programs\/international-cancer-proteogenome-consortium\"><span style=\"font-weight: 400;\">International Cancer Proteogenome Consortium<\/span><\/a><span style=\"font-weight: 400;\"> (ICPC), a global effort to accelerate the understanding of the molecular basis of cancer through the application of proteogenomics. These flagship studies have advanced the field by developing cutting-edge computational methods. PANOPLY combines representative methods from these studies, which originated as disparate algorithms implemented by different research groups, into a unified pipeline within a computational framework built to be modular, scalable and reproducible.\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400;\">PANOPLY takes as input a set of pre-formatted datasets derived from DNA, RNA and protein profiling, along with phenotype and clinical annotations (see Figure 1). Any normalization or filtering for proteomics data is accomplished using Data Preparation Modules. Analysis ready data is then channelled to a series of Data Analysis Modules, many of which perform integrated multi-omic analysis. Almost all analysis modules output an interactive HTML report summarizing results, in addition to detailed tables and plots.<\/span><\/p>\n<p>&nbsp;<\/p>\n<p><img fetchpriority=\"high\" decoding=\"async\" class=\"alignnone size-full wp-image-952\" src=\"https:\/\/terra.bio\/wp-content\/uploads\/2023\/12\/panoply-fig1.jpg\" alt=\"Diagram of Panoply modular architecture\" width=\"921\" height=\"512\" \/><\/p>\n<p><span style=\"font-weight: 400;\">Figure 1. PANOPLY architecture overview, showing various data types used along with modules for data pre-processing and analysis.<\/span><\/p>\n<p>&nbsp;<\/p>\n<p><span style=\"font-weight: 400;\">We implemented each module as a standalone workflow, and we created one unified workflow that imports all the module workflows into a full end-to-end pipeline. This enables researchers to easily apply the full complement of proteogenomics analyses to their data out of the box, which we expect to be the majority use case.\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400;\">We also anticipated that some researchers might want to apply individual methods to a variety of use cases, so to provide that flexibility, we designed the individual modules to be runnable by themselves.\u00a0 We also made it possible to compose custom pipelines that include these modules in combination with other modules that researchers might write or publish themselves. This way, researchers can take advantage of the groundbreaking work done by various CPTAC groups, and they can build on that work to further advance the field, with less effort spent on figuring out tooling.<\/span><\/p>\n<p><span style=\"font-weight: 400;\">All workflows are written in <\/span><a href=\"https:\/\/support.terra.bio\/hc\/en-us\/articles\/360037117492-Getting-Started-with-WDL\"><span style=\"font-weight: 400;\">WDL<\/span><\/a><span style=\"font-weight: 400;\"> and use containerized tools, so they can be run on any standard computational platform. All code \u2014 including algorithm implementations and WDLs \u2014 is open source and available in <\/span><a href=\"https:\/\/github.com\/broadinstitute\/PANOPLY\"><span style=\"font-weight: 400;\">GitHub<\/span><\/a><span style=\"font-weight: 400;\">.<\/span><\/p>\n<p>&nbsp;<\/p>\n<h3><span style=\"font-weight: 400;\">Leveraging Terra workspaces to increase access and usability\u00a0<\/span><\/h3>\n<p><span style=\"font-weight: 400;\">We recognized that enabling a wide range of people to use PANOPLY, especially those with less computational experience, would require more than just releasing code. We wanted a way to make PANOPLY usable out of the box, with tutorials that bundle example data, and we wanted to be able to update all of it easily whenever we make improvements to the software.<\/span><\/p>\n<p><span style=\"font-weight: 400;\">To that end, we put together 3 main resource workspaces that are all publicly available in Terra (see Figure 2): (i) a &#8220;Modules&#8221; workspace containing separate workflows for each analysis module; (ii) a &#8220;Pipelines&#8221; workspace with preconfigured unified pipelines for fast and easy execution and (iii) a &#8220;Tutorial&#8221; workspace showing inputs and outputs for the tutorial dataset. In order to further simplify the process of setting up a new analysis workspace, we used the \u201cNotebooks\u201d feature of Terra to provide a startup notebook that includes a step-by-step guide for users.\u00a0<\/span><\/p>\n<p>&nbsp;<\/p>\n<p><img decoding=\"async\" class=\"alignnone size-large wp-image-953\" src=\"https:\/\/terra.bio\/wp-content\/uploads\/2023\/12\/panoply-fig2-1024x325.png\" alt=\"Summary representation of the 3 types of workspaces provided with Panoply\" width=\"800\" height=\"254\" \/><\/p>\n<p><span style=\"font-weight: 400;\">Figure 2. Organization and contents of the PANOPLY workspaces on Terra.\u00a0<\/span><\/p>\n<p>&nbsp;<\/p>\n<p><span style=\"font-weight: 400;\">The tutorial dataset is centered on TCGA samples that were also subjected to proteomics profiling, adapted from our first proteogenomics publication on breast cancer (BRCA) (Mertins et al., 2016), and comes with everything needed to run the unified PANOPLY pipeline. The tutorial itself is organized as an easy to follow step-by-step procedure starting from cloning the workspace to uploading the data and running the pipeline. There is also documentation on expected results and how to interpret the many interactive reports generated by PANOPLY.<\/span><\/p>\n<p><span style=\"font-weight: 400;\">In addition to these core resources, we also provide additional &#8220;case study&#8221; workspaces showcasing the analysis of BRCA samples (Krug et al., 2020) that were freshly collected exclusively for proteogenomic analysis, along with analysis of a lung adenocarcinoma (LUAD) cohort (Gillette et al., 2020).\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400;\">We encourage you to check out the workspaces and try out the tutorial for yourself. If you&#8217;d like to share some feedback, please email us <\/span><a href=\"mailto:proteogenomics@broadinstitute.org\"><span style=\"font-weight: 400;\">proteogenomics@broadinstitute.org<\/span><\/a><span style=\"font-weight: 400;\">; we look forward to hearing from you.<\/span><\/p>\n<p>&nbsp;<\/p>\n<hr \/>\n<p>&nbsp;<\/p>\n<h4><span style=\"color: #008000;\">Resources<\/span><\/h4>\n<p>&nbsp;<\/p>\n<h5><span style=\"font-weight: 400;\">PANOPLY paper<\/span><\/h5>\n<p><span style=\"font-weight: 400;\">Mani, D.R., Maynard, M., Kothadia, R. <\/span><i><span style=\"font-weight: 400;\">et al.<\/span><\/i><span style=\"font-weight: 400;\"> PANOPLY: a cloud-based platform for automated and reproducible proteogenomic data analysis. <\/span><i><span style=\"font-weight: 400;\">Nat Methods<\/span><\/i><span style=\"font-weight: 400;\"> (2021). <\/span><a href=\"https:\/\/doi.org\/10.1038\/s41592-021-01176-6\"><span style=\"font-weight: 400;\">https:\/\/doi.org\/10.1038\/s41592-021-01176-6<\/span><\/a><span style=\"font-weight: 400;\">\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400;\">See also the<\/span> <a href=\"https:\/\/www.biorxiv.org\/content\/10.1101\/2020.12.04.410977v1\"><span style=\"font-weight: 400;\">preprint in biorxiv<\/span><\/a><span style=\"font-weight: 400;\">.<\/span><\/p>\n<p>&nbsp;<\/p>\n<h5><span style=\"font-weight: 400;\">Blog references<\/span><\/h5>\n<p><span style=\"font-weight: 400;\">Mertins, P. et al. Proteogenomics connects somatic mutations to signalling in breast cancer. <\/span><i><span style=\"font-weight: 400;\">Nature<\/span><\/i><span style=\"font-weight: 400;\"> 534, 55\u201362 (2016).<\/span><\/p>\n<p><span style=\"font-weight: 400;\">Krug, K. et al. Proteogenomic Landscape of Breast Cancer Tumorigenesis and Targeted Therapy. <\/span><i><span style=\"font-weight: 400;\">Cell<\/span><\/i><span style=\"font-weight: 400;\"> 183, 1\u201321 (2020).<\/span><\/p>\n<p><span style=\"font-weight: 400;\">Gillette, M. A. et al. Proteogenomic Characterization Reveals Therapeutic Vulnerabilities in Lung Adenocarcinoma. <\/span><i><span style=\"font-weight: 400;\">Cell<\/span><\/i><span style=\"font-weight: 400;\"> 182, 200\u2013225.e35 (2020).<\/span><\/p>\n<p>&nbsp;<\/p>\n<h5><span style=\"font-weight: 400;\">Full list of PANOPLY workspaces<\/span><\/h5>\n<table>\n<tbody>\n<tr>\n<td rowspan=\"2\"><b>PANOPLY Release v1.0<\/b><\/td>\n<td><span style=\"font-weight: 400;\">PANOPLY pipelines<\/span><\/td>\n<td><a href=\"https:\/\/app.terra.bio\/#workspaces\/broad-firecloud-cptac\/PANOPLY_Production_Pipelines_v1_0\"><span style=\"font-weight: 400;\">PANOPLY_Production_Pipelines_v1_0<\/span><\/a><\/td>\n<td><span style=\"font-weight: 400;\">Terra workspace with pre-configured pipelines, including startup notebook for easy data input and workspace configuration<\/span><\/td>\n<\/tr>\n<tr>\n<td><span style=\"font-weight: 400;\">PANOPLY modules<\/span><\/td>\n<td><a href=\"https:\/\/app.terra.bio\/#workspaces\/broad-firecloud-cptac\/PANOPLY_Production_Modules_v1_0\"><span style=\"font-weight: 400;\">PANOPLY_Production_Modules_v1_0<\/span><\/a><\/td>\n<td><span style=\"font-weight: 400;\">Terra workspace with all individual modules. This enables users to pick and choose modules and customize execution, but requires more knowledge of setting up inputs.\u00a0<\/span><\/td>\n<\/tr>\n<tr>\n<td rowspan=\"2\"><b>Tutorial<\/b><\/td>\n<td><span style=\"font-weight: 400;\">Tutorial description<\/span><\/td>\n<td><a href=\"https:\/\/github.com\/broadinstitute\/PANOPLY\/wiki\/PANOPLY-Tutorial\"><span style=\"font-weight: 400;\">PANOPLY-Tutorial (Github wiki)<\/span><\/a><\/td>\n<td><span style=\"font-weight: 400;\">Step-by-step instructions for running the PANOPLY tutorial<\/span><\/td>\n<\/tr>\n<tr>\n<td><span style=\"font-weight: 400;\">Tutorial workspace<\/span><\/td>\n<td><a href=\"https:\/\/app.terra.bio\/#workspaces\/broad-firecloud-cptac\/PANOPLY_Tutorial\"><span style=\"font-weight: 400;\">PANOPLY_Tutorial<\/span><\/a><\/td>\n<td><span style=\"font-weight: 400;\">Terra workspace with tutorial instructions, data, analysis and results<\/span><\/td>\n<\/tr>\n<tr>\n<td rowspan=\"2\"><b>Case Studies<\/b><\/td>\n<td><span style=\"font-weight: 400;\">BRCA<\/span><\/td>\n<td><a href=\"https:\/\/app.terra.bio\/#workspaces\/broad-firecloud-cptac\/PANOPLY_CPTAC_BRCA\"><span style=\"font-weight: 400;\">PANOPLY_CPTAC_BRCA<\/span><\/a><\/td>\n<td><span style=\"font-weight: 400;\">Terra workspace with data, analysis and results from the (Krug, et al,., 2020, <\/span><i><span style=\"font-weight: 400;\">Cell<\/span><\/i><span style=\"font-weight: 400;\">) breast cancer study<\/span><\/td>\n<\/tr>\n<tr>\n<td><span style=\"font-weight: 400;\">LUAD<\/span><\/td>\n<td><a href=\"https:\/\/app.terra.bio\/#workspaces\/broad-firecloud-cptac\/PANOPLY_CPTAC_LUAD\"><span style=\"font-weight: 400;\">PANOPLY_CPTAC_LUAD<\/span><\/a><\/td>\n<td><span style=\"font-weight: 400;\">Terra workspace with data, analysis and results from the (Gillette, et al,., 2020, <\/span><i><span style=\"font-weight: 400;\">Cell<\/span><\/i><span style=\"font-weight: 400;\">) lung adenocarcinoma\u00a0 study<\/span><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>PANOPLY is a computational framework for applying statistical and machine learning algorithms to transform multi-omic data from cancer samples into biologically meaningful and interpretable results. In this post, D. R. Mani explains how his team is leveraging Terra to make PANOPLY accessible to a wide range of researchers.<\/p>\n","protected":false},"author":25,"featured_media":355,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[68,106,13,19,45,123,58,38,32,14],"tags":[124,125,126,127,128],"class_list":["post-352","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-cancer","category-genomics","category-guest-author","category-most-popular","category-notebooks","category-proteomics","category-publications","category-tutorials","category-workflows","category-workspaces","tag-brca","tag-computational-framework","tag-cptac","tag-luad","tag-tcga"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.0 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Spotlight on PANOPLY, a scalable framework for cancer proteogenomics - Terra<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/terra.bio\/panoply-framework-for-cancer-proteogenomics\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Spotlight on PANOPLY, a scalable framework for cancer proteogenomics - Terra\" \/>\n<meta property=\"og:description\" content=\"PANOPLY is a computational framework for applying statistical and machine learning algorithms to transform multi-omic data from cancer samples into biologically meaningful and interpretable results. 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