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PANOPLY: Omics-Guided Drug Prioritization Method Tailored to an Individual Patient
Krishna R Kalari1, Jason P Sinnwell1, Kevin J Thompson1
1All authors: Mayo Clinic, Rochester, MN.
Purpose:
The majority of patients with cancer receive treatments that are minimally informed by omics data. We propose a precision medicine computational framework, PANOPLY (Precision Cancer Genomic Report: Single Sample Inventory), to identify and prioritize drug targets and cancer therapy regimens.
Materials And Methods:
The PANOPLY approach integrates clinical data with germline and somatic features obtained from multiomics platforms and applies machine learning and network analysis approaches in the context of the individual patient and matched controls. The PANOPLY workflow uses the following four steps: selection of matched controls to the patient of interest; identification of patient-specific genomic events; identification of suitable drugs using the driver-gene network and random forest analyses; and provision of an integrated multiomics case report of the patient with prioritization of anticancer drugs.
Results:
The PANOPLY workflow can be executed on a stand-alone virtual machine and is also available for download as an R package. We applied the method to an institutional breast cancer neoadjuvant chemotherapy study that collected clinical and genomic data as well as patient-derived xenografts to investigate the prioritization offered by PANOPLY. In a chemotherapy-resistant patient-derived xenograft model, we found that that the prioritized drug, olaparib, was more effective than placebo in treating the tumor ( P < .05). We also applied PANOPLY to in-house and publicly accessible multiomics tumor data sets with therapeutic response or survival data available.
Conclusion:
PANOPLY shows promise as a means to prioritize drugs on the basis of clinical and multiomics data for an individual patient with cancer. Additional studies are needed to confirm this approach.
Insights
PANOPLY is a computational framework that uses omics data to guide cancer treatment. It prioritizes drugs for individual patients, showing promise in preclinical models.
Area of Science:
- Oncology
- Computational Biology
- Genomics
Background:
- Current cancer treatments often lack personalization, with limited integration of omics data.
- Precision medicine aims to tailor treatments based on individual patient molecular profiles.
Purpose of the Study:
- To introduce PANOPLY (Precision Cancer Genomic Report: Single Sample Inventory), a computational framework for precision cancer medicine.
- To identify and prioritize drug targets and cancer therapy regimens informed by multiomics data.
Main Methods:
- PANOPLY integrates clinical, germline, and somatic multiomics data.
- It employs machine learning and network analysis, comparing patients to matched controls.
- The workflow involves control selection, identification of patient-specific genomic events, drug suitability analysis, and report generation.
Main Results:
- PANOPLY was applied to a breast cancer study and a chemotherapy-resistant xenograft model.
- The framework successfully prioritized olaparib, which showed significant efficacy over placebo in a preclinical model.
- The workflow is available as a virtual machine or R package.
Conclusions:
- PANOPLY demonstrates potential for prioritizing anticancer drugs based on individual patient multiomics data.
- Further clinical studies are necessary to validate the approach's efficacy in patient care.
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