PDXNet portal: patient-derived Xenograft model, data, workflow and tool discovery

Abstract

We created the PDX Network (PDXNet) portal (https://portal.pdxnetwork.org/) to centralize access to the National Cancer Institute-funded PDXNet consortium resources, to facilitate collaboration among researchers and to make these data easily available for research. The portal includes sections for resources, analysis results, metrics for PDXNet activities, data processing protocols and training materials for processing PDX data. Currently, the portal contains PDXNet model information and data resources from 334 new models across 33 cancer types. Tissue samples of these models were deposited in the NCI's Patient-Derived Model Repository (PDMR) for public access. These models have 2134 associated sequencing files from 873 samples across 308 patients, which are hosted on the Cancer Genomics Cloud powered by Seven Bridges and the NCI Cancer Data Service for long-term storage and access with dbGaP permissions. The portal includes results from freely available, robust, validated and standardized analysis workflows on PDXNet sequencing files and PDMR data (3857 samples from 629 patients across 85 disease types). The PDXNet portal is continuously updated with new data and is of significant utility to the cancer research community as it provides a centralized location for PDXNet resources, which support multi-agent treatment studies, determination of sensitivity and resistance mechanisms, and preclinical trials.

Graphical Abstract

The PDXNet portal provides a way for researchers to learn about the PDX models, sequencing data and PDX Minimum Information metadata tools generated by the network for public use.

Figure 1.

PDXNet Portal Landing Page Views from the PDXNet Portal Landing Page. (A) The initial PDXNet Portal Landing Page. (B) Experimental strategies (whole-exome and RNA-Seq) for the PDXNet (magenta) and PDMR (gray) sequencing datasets. (C) Computed ancestry in a pie chart. Ancestry is classified in the following categories: European (EUR-Red), African (AFR-Blue), American (AMR-Purple), Mixed (MIX-Orange), East Asian (EAS-Light Purple), South Asian (SAS-Yellow).

Figure 2.

PDXNet sequencing data page on the PDXNet Portal Components of the PDXNet sequencing data page. (A) Panel shows summary statistics including number of sequencing files (green), contributors (yellow), total samples (orange) and total patients (blue). Also, shown are donut plots for contributors, sample types, disease type, experimental strategy, WES contributors and RNA-Seq contributors. (B) Panel shows metadata for the PDXNet sequencing data in a spreadsheet format. The interface supports searching and sorting metadata. Users can copy, print, and download metadata into accessible formats.

Figure 3.

Examples figures generated from the HRD-TMB-MSI page on the PDXNet Portal Plots generated on the PDXNet Portal HRD-TMB-MSI page. (A) Plot of Homologous Recombination Deficiency (HRD) computed from sequencing data provided by PDXNet researchers. The plot shows HRD by disease type. (B) Plot of Tumor Mutational Burden (TMB) computed from sequencing data provided by PDXNet researchers. The plot shows TMB by disease type. (C) Plot of TMB computed from sequencing data provided by PDXNet researchers, by disease type.

Figure 4.

Tumor volume data page on the PDXNet Portal Components of the PDXNet tumor volume page. The figure shows a filtered dataset. (A) Panel shows summary statistics including number tumor volume datasets (green), number of models in the selected dataset (yellow), total number of patients (blue), and total number of diseases represented (red). (B) Panel shows the tumor volume data organized by study and automatically computed resist category for each treatment arm. (C) Panel shows the tumor volume response and metadata in a spreadsheet format. The interface supports searching and sorting metadata. Users can copy, print, and download metadata into accessible formats