PRIMAVO: Interactive exploration of cancer patient precision immune monitoring data in clinical trials

PRIMAVO：临床试验中癌症患者精准免疫监测数据的互动探索

基本信息

批准号：
10294555
负责人：
Zeynep Hulya Gumus
金额：
$ 154.25万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-23 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10294555
关键词：
16S ribosomal RNA sequencing Address Antigens Award Biological Assay Biological Markers Cancer Patient Cancer Therapy Evaluation Program Clinical Clinical Trials Clinical Trials Design Colitis Communication Communities Computer Analysis Custom Cytometry Data Data Analyses Data Commons Data Set Development Dimensions Disease Enzyme-Linked Immunosorbent Assay Event Feedback Flow Cytometry Future Grant Growth Immune Immune response Immune system Immunologic Markers Immunologic Monitoring Immunologics Immunology Immunooncology Immunotherapy Infrastructure Interview Malignant Neoplasms Metagenomics Minority Mission Monitor Mutation Online Systems Output Participant Patients Principal Component Analysis Proteomics Public Health Research Research Personnel Serology Shotguns Standardization Surveys Technology Time Toxic effect Translating Visual Visualization Visualization software analysis pipeline anticancer research base biomarker discovery cancer care cancer immunotherapy clinical practice clinical trial participant clinically actionable cohort data exploration data visualization demographics design diverse data exome experience flexibility high dimensionality immune checkpoint blockade immune-related adverse events immunotherapy clinical trials immunotherapy trials improved interactive tool interest medical schools microbiome analysis novel marker novel therapeutics response response biomarker side effect skills tool tool development transcriptome sequencing treatment response tumor user-friendly web-based tool

项目摘要

PROJECT SUMMARY Cancer immunotherapies have dramatically changed clinical practice following the approval of more than a dozen new drugs and/or indications in the past few years1–4. However, only a minority of patients derives clinical benefit, while some develop off-target effects. To identify novel biomarkers of disease course and response, as well as potential off-target responses to immunotherapy in cancer patients, the NCI’s Cancer Moonshot Initiative (CMI) is supporting a growing number of cancer immunotherapy trials. Our team is at the forefront of the CMI efforts with two grants: 1) a U24 on high-dimensional immune monitoring of NCI-supported immunotherapy trials as part of the Cancer Therapy Evaluation Program (CTEP); and 2) a U01 on characterizing and predicting a toxic side-effect of immunotherapy, colitis, in immune checkpoint blockade- treated cancer patients, as part of the Immuno-Oncology Translational Network (IOTN). However, with the rapid development of new and improved technologies, these studies produce diverse data types of ever- expanding size and complexity. Visualizing, exploring, and communicating results from the computational analysis of these disparate high-dimensional immune monitoring assays is imperative but challenging, especially because many visualization tools are either built only for in-house utilization or typically specialize in only one or perhaps a few data types. At the same time, cross-assay or cross-participant data interpretation is the only way to identify relevant immune biomarkers that impact clinical trial design and clinical cancer care. There is thus an unmet need for easy-to-use interactive tools for integrative exploration of cancer patient immune monitoring data by biologists and clinicians. This proposal aims to address this need through the development of a user-friendly, integrative web-based visualization tool, Precision Immunology Monitoring Analysis and Visualization Online (PRIMAVO), that will enable researchers of all computational skill levels to visually analyze and interactively explore immune monitoring assay results that belong to a cancer immunotherapy trial, at multiple levels of granularity. The PRIMAVO tool will scale with current and future data growth and complexity to enable fast and effective research towards identifying associations between different data types, participants, and clinical variables. We hypothesize that developing (i) cohort-level; and (ii) participant-level visualizations that integrate views across multiple immune data types, participants, cohorts and time points will provide a deep, comprehensive view of events; and that (iii) the content and features of PRIMAVO will be greatly enhanced by engaging with the user community during its development. The results from this highly integrated effort will have important clinical and public health implications by accelerating our understanding of the immune responses of cancer patients to immunotherapies and significantly impact the rate at which immune biomarkers from clinical trials will be identified, interpreted, verified and translated into clinically actionable findings. Overall, PRIMAVO will be a highly valuable tool for the research community.

项目摘要在批准超过多次之后，癌症免疫疗法已大大改变了临床实践在过去的几年中，十二种新药和/或适应症1-4。但是，只有少数患者得出临床益处，而某些开发脱离靶向。确定新型疾病课程的生物标志物和 NCI癌症的反应以及对癌症患者免疫疗法的潜在反应反应 Moonshot Initiative（CMI）正在支持越来越多的癌症免疫疗法试验。我们的团队在 CMI努力的最前沿，并提供两项赠款：1）在NCI支持的高维免疫监测上的U24 免疫疗法试验是癌症治疗评估计划（CTEP）的一部分； 2）u01 特征和预测免疫疗法的有毒副作用，结肠炎治疗癌症患者，作为免疫肿瘤转化网络（IOTN）的一部分。但是，与这些研究快速开发了新的和改进的技术，生产了潜水员数据类型的不断发展扩大大小和复杂性。可视化，探索和传达计算的结果对这些不同高维的免疫免疫监测测定法的分析是必须的，但要挑战，但尤其是因为许多可视化工具要么仅用于内部利用，要么通常专门从事只有一种或可能的数据类型。同时，跨标准或跨参与者数据解释为识别影响临床试验设计和临床癌症护理的相关免疫生物标志物的唯一方法。因此，需要易于使用的易于使用的交互式工具来整合癌症患者的综合探索生物学家和临床医生的免疫监测数据。该建议旨在通过开发用户友好，集成的基于Web的可视化工具，精确免疫学监测在线分析和可视化（Primavo），这将使所有计算技能水平的研究人员都能达到视觉分析并交互探索属于癌症的免疫监测测定结果免疫疗法试验，在多个粒度上。 Primavo工具将通过当前和将来的数据扩展增长和复杂性，使能够快速有效的研究以确定不同的关联数据类型，参与者和临床变量。我们假设发展（i）队列级别；（ii）参与者级的可视化效应，这些可视化涉及多种免疫数据类型，参与者，人群的视图时间点将提供对事件的深刻，全面的看法；（iii）的内容和特征 Primavo在开发过程中与用户社区互动会大大增强。结果通过这项高度综合的努力将通过加速我们的重要临床和公共卫生影响了解癌症患者免疫调查的免疫疗法，并显着影响将确定，解释，验证和翻译成临床试验的免疫生物标志物的速率临床可行的发现。总体而言，Primavo将成为研究界的高度有价值工具。