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Published on: April 11, 2016
TQuest, A Web-Based Platform to Enable Precision Medicine by Linking a Tumor's Genetic Defects to Therapeutic Options
Peter Gershkovich1, James Platt1, Joshua Knopf1
1Peter Gershkovich, Joshua Knopf, Lajos Pusztai, Christos Hatzis, Yale School of Medicine, New Haven; James Platt, Biomantica, West Haven, CT; Marios K. Tasoulis, The Royal Marsden National Health Services Foundation Trust, London, United Kingdom; and Weiwei Shi, Origimed, Shanghai, China.
Purpose:
Currently, there are only a few software tools designed to assist physicians to translate molecular abnormalities in the cancer genome into potential treatment options. There is a pressing need to develop software to reliably identify known targeted therapies and experimental treatments for patients on the basis of the results of tumor DNA sequencing.
Methods:
The TQuest platform includes a data layer, data acquisition layer, search engine, and user interface. It identifies associations between one or more molecular targets and therapeutic options. The data layer consists of indexed interventional clinical trials and an expert-curated database of clinically or experimentally validated associations between mutations and drug response. The data acquisition layer includes an information-harvesting module that keeps an up-to-date full-text index of clinical trials by crawling clinicaltrials.gov and combining it with US Food and Drug Administration label data. The user interface is a Web-based module that allows users to upload genomic variants, tumor morphology, and diagnosis. The search results are qualified and ranked by a relevance score.
Results:
We have manually curated information for 368 distinct genomic variants of 162 gene targets corresponding to 863 drug and target interactions. The platform currently contains a full-text index of approximately 80,000 interventional clinical trials. We applied TQuest to molecular data from 73 metastatic breast cancers. TQuest identified a total of 276 drugs as potential therapeutic options, ranging from one to 103 per patient.
Conclusion:
TQuest correctly identified all US Food and Drug Administration-approved drugs and routine indications for all cases and also identified many additional drugs that were used in the context of a given molecular abnormality in various clinical trials. The prototype Web application is available at www.tquest.us , and the source code is open and available on GitHub.
Insights
TQuest software translates cancer genomic variants into targeted therapy options. It identifies FDA-approved and experimental treatments from clinical trials, aiding precision medicine.
Area of Science:
- Bioinformatics
- Computational Biology
- Genomics
Background:
- Limited software exists to link cancer genomic alterations to treatment strategies.
- A need for tools to identify targeted therapies based on tumor DNA sequencing is critical for precision oncology.
Purpose of the Study:
- To develop and evaluate the TQuest platform for translating molecular abnormalities into potential cancer treatment options.
- To create a reliable software solution for identifying targeted and experimental therapies using tumor DNA sequencing data.
Main Methods:
- The TQuest platform integrates a data layer (clinical trials, curated mutation-drug associations), a data acquisition layer (crawling clinicaltrials.gov, FDA labels), and a web-based user interface.
- Users upload genomic variants, tumor morphology, and diagnosis; the system searches and ranks therapeutic options based on relevance.
Main Results:
- Manual curation yielded 368 genomic variants, 162 gene targets, and 863 drug-target interactions.
- The platform indexed ~80,000 clinical trials and identified 276 potential drugs for 73 metastatic breast cancer cases (1-103 drugs per patient).
Conclusions:
- TQuest successfully identified all FDA-approved drugs and routine indications, plus numerous experimental treatments from clinical trials.
- The TQuest prototype is available online, with open-source code, facilitating its adoption in clinical practice.
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