Assessment of Patient-Derived Xenograft Growth and Antitumor Activity: The NCI PDXNet Consensus Recommendations.

Although patient-derived xenografts (PDXs) are commonly used for preclinical modeling in cancer research, a standard approach to in vivo tumor growth analysis and assessment of antitumor activity is lacking, complicating comparison of different studies and determination of whether a PDX experiment has produced evidence needed to consider a new therapy promising. We present consensus recommendations for assessment of PDX growth and antitumor activity, providing public access to a suite of tools for in vivo growth analyses. We expect that harmonizing PDX study design and analysis and access to a suite of analytical tools will enhance information exchange and facilitate identification of promising novel therapies and biomarkers for guiding cancer therapy.

Artificial intelligence assisted patient blood and urine droplet pattern analysis for non-invasive and accurate diagnosis of bladder cancer.

Bladder cancer is one of the most common cancer types in the urinary system. Yet, current bladder cancer diagnosis and follow-up techniques are time-consuming, expensive, and invasive. In the clinical practice, the gold standard for diagnosis remains invasive biopsy followed by histopathological analysis. In recent years, costly diagnostic tests involving the use of bladder cancer biomarkers have been developed, however these tests have high false-positive and false-negative rates limiting their reliability. Hence, there is an urgent need for the development of cost-effective, and non-invasive novel diagnosis methods. To address this gap, here we propose a quick, cheap, and reliable diagnostic method. Our approach relies on an artificial intelligence (AI) model to analyze droplet patterns of blood and urine samples obtained from patients and comparing them to cancer-free control subjects. The AI-assisted model in this study uses a deep neural network, a ResNet network, pre-trained on ImageNet datasets. Recognition and classification of complex patterns formed by dried urine or blood droplets under different conditions resulted in cancer diagnosis with a high specificity and sensitivity. Our approach can be systematically applied across droplets, enabling comparisons to reveal shared spatial behaviors and underlying morphological patterns. Our results support the fact that AI-based models have a great potential for non-invasive and accurate diagnosis of malignancies, including bladder cancer.

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

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.

Bioinformatics tools developed to support BioCompute Objects.

Developments in high-throughput sequencing (HTS) result in an exponential increase in the amount of data generated by sequencing experiments, an increase in the complexity of bioinformatics analysis reporting and an increase in the types of data generated. These increases in volume, diversity and complexity of the data generated and their analysis expose the necessity of a structured and standardized reporting template. BioCompute Objects (BCOs) provide the requisite support for communication of HTS data analysis that includes support for workflow, as well as data, curation, accessibility and reproducibility of communication. BCOs standardize how researchers report provenance and the established verification and validation protocols used in workflows while also being robust enough to convey content integration or curation in knowledge bases. BCOs that encapsulate tools, platforms, datasets and workflows are FAIR (findable, accessible, interoperable and reusable) compliant. Providing operational workflow and data information facilitates interoperability between platforms and incorporation of future dataset within an HTS analysis for use within industrial, academic and regulatory settings. Cloud-based platforms, including High-performance Integrated Virtual Environment (HIVE), Cancer Genomics Cloud (CGC) and Galaxy, support BCO generation for users. Given the 100K+ userbase between these platforms, BioCompute can be leveraged for workflow documentation. In this paper, we report the availability of platform-dependent and platform-independent BCO tools: HIVE BCO App, CGC BCO App, Galaxy BCO API Extension and BCO Portal. Community engagement was utilized to evaluate tool efficacy. We demonstrate that these tools further advance BCO creation from text editing approaches used in earlier releases of the standard. Moreover, we demonstrate that integrating BCO generation within existing analysis platforms greatly streamlines BCO creation while capturing granular workflow details. We also demonstrate that the BCO tools described in the paper provide an approach to solve the long-standing challenge of standardizing workflow descriptions that are both human and machine readable while accommodating manual and automated curation with evidence tagging. Database URL:  https://www.biocomputeobject.org/resources.

BCO App: tools for generating BioCompute Objects from next-generation sequencing workflows and computations.

The BioCompute Object (BCO) standard is an IEEE standard (IEEE 2791-2020) designed to facilitate the communication of next-generation sequencing data analysis with applications across academia, government agencies, and industry. For example, the Food and Drug Administration (FDA) supports the standard for regulatory submissions and includes the standard in their Data Standards Catalog for the submission of HTS data. We created the BCO App to facilitate BCO generation in a range of computational environments and, in part, to participate in the Advanced Track of the precisionFDA BioCompute Object App-a-thon. The application facilitates the generation of BCOs from both workflow metadata provided as plaintext and from workflow contents written in the Common Workflow Language. The application can also access and ingest task execution results from the Cancer Genomics Cloud (CGC), an NCI funded computational platform. Creating a BCO from a CGC task significantly reduces the time required to generate a BCO on the CGC by auto-populating workflow information fields from CGC workflow and task execution results. The BCO App supports exporting BCOs as JSON or PDF files and publishing BCOs to both the CGC platform and to GitHub repositories.