Abstract 3017: Advancing PDX research through model, data, and bioinformatics with the PDXNet Portal

Abstract

Abstract We created the PDX Network (PDXNet) Portal to provide an intuitive way for researchers to explore and understand the models, sequencing data, and bioinformatics workflows generated by NCI's PDXNet consortium for research access (https://portal.pdxnetwork.org/). The portal also provides metrics for PDXNet's activities, data processing protocols, and training materials for processing PDX data. The PDXNet Portal highlights model and data resources that include 216 new models across 29 cancer types. The most prevalent cancers represented in the PDX model dataset include invasive breast carcinoma (30.6%), melanoma (18.1%), and adenocarcinoma (14.4%). PDXNet teams have provided 2263 sequencing files from 356 samples across 204 patients, comprising whole exome (82.9%) and RNA seq files (17.1%). The most prevalent cancers represented in the PDXNet sequencing data set include Breast Pleural Effusion (27.2%), Breast Poorly Differentiated (12.5%), and Lung Adenocarcinoma (9.6%). The portal also provides access to 9492 sequencing files across 78 disease types that include 2594 samples across 463 patients uploaded from the NCI Patient-Derived Model Repository. The dataset includes both whole exomes (52.8%) and RNA seq (47.2%) data. The PDMR samples include PDX (82.7%), primary tumor (5.7%), normal germline (5.5), organoid culture (3.2), and Mixed Tumor Culture (2.9). The PDMR dataset also has multiple passages: P0 (21.8%), P1(39.5%), P2 (25.6%), and P3 (8.5%). These models and data resources support ten PDXNet Pilot activities, multiple publications, and international collaborations. PDXNet has also developed a set of 13 robust, validated, and standardized workflows for processing PDXNet whole-exome and RNA seq data. Collectively, these workflows allow for the standardized processing of PDX and complementary human tissues (normal and tumor). Our plan is to continuously update the model and data lists on the PDX portal as resources are generated. We expect that the PDXNet generated models, scheduled to grow to 1000 new models by 2022, will support multi-agent treatment studies, determination of mechanisms of sensitivity and resistance, and pre-clinical trials for example through the COMBO-MATCH program. The robust standard workflows currently processing all PDX sequencing data may also facilitate harmonizing data across studies. Lastly, we expect that the generated sequencing data will support computational approaches for studying cancer evolution and the mechanisms underlying cancer treatments. Citation Format: Soner Koc, Mike Lloyd, Steven Neuhauser, Javad Noodbakhsh, Anuj Srivastava, Xing Yi Woo, Ryan Jeon, Jeffrey Grover, Sara Seepo, Christian Frech, Jack DiGiovanna, PDXNet Consortium, Yvonne A. Evard, Tiffany Wallace, Jeffrey Moscow, James H. Doroshow, Nicholas Mitsuade, Salma Kaochar, Chong-xian Pan, Moon S. Chen, Luis Carvarjal-Carmona, Alana Welm, Bryan Welm, Michael T. Lewis, Govindan Ramaswamy, Li Ding, Shunquang Li, Meenherd Herlyn, Mike Davies, Jack Roth, Funda Meric-Bernstam, Peter Robinson, Carol J. Bult, Brandi Davis-Dusenbery, Dennis A. Dean, Jeffrey H. Chuang. Advancing PDX research through model, data, and bioinformatics with the PDXNet Portal [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3017.