Rapid Acute Leukemia Genomic Profiling with CRISPR enrichment and Real-time long-read sequencing

利用 CRISPR 富集和实时长读长测序进行快速急性白血病基因组分析

基本信息

批准号：
10839678
负责人：
CECILIA C YEUNG
金额：
$ 24.46万
依托单位：
FRED HUTCHINSON CANCER CENTER
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10839678
关键词：
Acceleration Acute Myelocytic Leukemia Acute leukemia Adoption Award Benchmarking Big Data Bioinformatics Biological Assay Cell Line Chromosome abnormality Clinic Clinical Cloud Computing Cloud Service Clustered Regularly Interspaced Short Palindromic Repeats Communities Complex Computer software Computers Custom DNA Data Data Analyses Dedications Devices Diagnostic Documentation Environment Event Fogs Genes Genomics Hybrids Image Instruction Methods Molecular Abnormality Molecular Profiling Mutate Mutation Oncologist Parents Patient Transfer Patient-Focused Outcomes Patients Performance Phase Pilot Projects Process Prognosis Prognostic Marker Protocols documentation Provider Reporting Reproducibility Research Resources Running Sampling Secure Security Services Software Engineering Software Tools Specific qualifier value Specimen Technology Testing Time Variant Writing clinically relevant computerized data processing computing resources cost cost effective data exchange data reduction database of Genotypes and Phenotypes deep learning deep learning model detection method improved laptop mortality multiple omics nanopore open data open source parent grant performance tests portability predictive marker quality assurance single molecule software development treatment response

项目摘要

PROJECT SUMMARY The parent award (1R21CA280520-01) aims to develop fast and cost-effective methods of detecting Acute Myeloid Leukemia (AML) fusions and mutations to improve clinical outcomes for patients. The parent award builds on a CRISPR-based single molecule long-read sequencing assay (CSRL) to detect clinically relevant mutated genes in AML by including additional prognostic and predictive markers. The improved assay will be validated using known cell line mixes and patient samples. Aim 1 of the parent R21 will also create bioinformatics workflows to enable same day data analysis using the open-source Biodepot-workflow-builder (Bwb) platform. The Bwb platform will be extended to detect fusion and DNA variants. Aim 2 of the parent R21 will compare our assay performance to established clinical grade tests on archival specimens, and evaluate clinical impact of phasing data and fusion breakpoints on prognosis and treatment response. Aim 3 of the parent R21 will demonstrate the clinical impact of our molecular profiling assay and bioinformatics platform through a pilot study on samples from the clinic, ease of same day testing and reporting, and study of the impacts that same day results can potentially have on patient treatment. Our CSRL assay, combined with new bioinformatics approaches, will establish potential use in the clinic for an ultrarapid same-day informative molecular profiling assay for AML to guide oncologists for immediate therapy implementations. In this supplement, we will employ software engineering best practices to extend the Bwb platform to enable execution of modules on different platforms that are specified at runtime. Bioinformatics workflows will be able to simultaneously utilize different resources and leverage the enhanced security and reduced data transfer of local devices while benefiting from the scalability of the cloud. This hybrid cloud computing approach would be beneficial for the parent R21 as steps involving large files (basecalling and alignment) could be done locally on a GPU enabled laptop, server, or dedicated device resulting in the transfer of smaller files to the cloud for computationally intensive deep-learning based variant calling. Bwb currently has specialized workflows with modules that run simultaneously on the cloud and locally. The supplement will allow users to specify the execution platform for modules at runtime without the need to re-write the workflow. We will support a full-time research software engineer and add a new collaborator with expertise in software engineering and cloud computing. This hybrid cloud implementation will be applied and benchmarked using data generated in the parent award and the test suite will be saved and distributed as part of the workflow. We will also provide a single sign-on service to simplify the additional authentication needed for execution on multiple platforms. All software developed will be public and open-source. These improvements will provide a robust open-source platform for other multi-omics and imaging data workflows to leverage emerging hybrid cloud and edge computing technologies.

项目概要家长奖 (1R21CA280520-01) 旨在开发快速且经济高效的急性急性发作检测方法髓系白血病 (AML) 融合和突变可改善患者的临床结果。家长奖基于 CRISPR 的单分子长读长测序分析 (CSRL) 构建，以检测临床相关通过添加额外的预后和预测标记来抑制 AML 中的突变基因。改进的测定将是使用已知的细胞系混合物和患者样本进行验证。母公司 R21 的目标 1 还将创建生物信息学使用开源 Biodepot-workflow-builder (Bwb) 平台实现当天数据分析的工作流程。 Bwb 平台将扩展至检测融合和 DNA 变异。母体 R21 的目标 2 将比较我们的分析性能以建立档案标本的临床等级测试，并评估临床影响关于预后和治疗反应的分阶段数据和融合断点。母公司 R21 的目标 3 将通过试点研究展示我们的分子分析测定和生物信息学平台的临床影响关于诊所的样本、当天测试和报告的便利性以及当天影响的研究结果可能会对患者的治疗产生影响。我们的 CSRL 检测结合新的生物信息学方法，将在临床中建立超快速当天信息分子分析的潜在用途 AML 检测可指导肿瘤学家立即实施治疗。在本补充材料中，我们将采用软件工程最佳实践来扩展 Bwb 平台，以实现在运行时指定的不同平台上执行模块。生物信息学工作流程将能够同时利用不同的资源并利用增强的安全性和减少的数据传输本地设备，同时受益于云的可扩展性。这种混合云计算方法将是对父 R21 有利，因为涉及大文件的步骤（碱基调用和比对）可以在本地完成支持 GPU 的笔记本电脑、服务器或专用设备，可将较小的文件传输到云中基于计算密集型深度学习的变体调用。 Bwb 目前拥有专门的工作流程在云端和本地同时运行的模块。该补充将允许用户指定模块在运行时的执行平台，无需重新编写工作流程。我们将支持全职研究软件工程师并添加一位具有软件工程和云专业知识的新合作者计算。这种混合云实施将使用中生成的数据进行应用和基准测试家长奖励和测试套件将作为工作流程的一部分保存和分发。我们还将提供单登录服务可简化在多个平台上执行所需的额外身份验证。所有软件开发的将是公共和开源的。这些改进将为其他多组学和成像数据工作流程，以利用新兴的混合云和边缘计算技术。