Detection of somatic, subclonal and mosaic CNVs from sequencing

通过测序检测体细胞、亚克隆和嵌合 CNV

基本信息

批准号：
10399434
负责人：
ALEXEJ ABYZOV
金额：
$ 56.14万
依托单位：
MAYO CLINIC ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-05-01 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10399434
关键词：
Address Aftercare Area Attention Basic Science Biology Cancer Diagnostics Cells Clinic Clinical Clinical Research Clinical Treatment Collaborations Colon Carcinoma Colorectal Cancer Communities Computer software Copy Number Polymorphism Coupled Data Detection Development Disease Documentation Effectiveness Environment Foundations Frequencies Future Gene Frequency Genetic Variation Genome Genomics Goals Health Human Human Genetics Human body Individual Lead Life Maintenance Malignant Neoplasms Malignant neoplasm of ovary Medical Medicine Methods Mosaicism Neoplasm Metastasis Organ Patients Performance Persons Polyps Predisposition Procedures Process Prognosis Quality Control Quality of life Relapse Reporting Research Research Project Grants Residual state Resolution Sampling Scientist Screening for cancer Signal Transduction Structure Techniques Technology Testing Tissues Variant analytical tool cancer invasiveness chemotherapy clinical care clinical diagnostics clinical practice clinically relevant computer framework digital disorder prevention exome sequencing expectation genetic variant genome sequencing individual response individualized medicine neuroendocrine cancer novel parallelization personalized medicine reference genome side effect simulation software development tool treatment choice treatment response tumor progression whole genome

项目摘要

Project Summary/Abstract Progress in technology has made individual genome sequencing a clinical reality, with partial genome sequencing already in use in clinical care. In fact, it is expected that within a few years whole genome sequencing will be a standard procedure that will allow discovering personal genomic variants of all types and thus greatly facilitate individualized medicine. However, fast and reliable analysis of such data is challenging; and improvements in analytics are needed before the clinical potential of whole genome sequencing can be realized. Specifically, copy number variations account for a large proportion of human genetic diversity, are frequently observed in cancer, and have been associated with multiple diseases, cancer susceptibility, cancer progression and invasiveness, individual response to treatment, and patients' quality of life after treatment (i.e., emergence of side effects). Therefore, comprehensive identification and analysis of copy-number variants will help us more fully elucidate the biology of their functional effects on human health (in particular, for cancer emergence and progression) and will facilitate clinical diagnostics and treatment. However, abilities to detect CNVs/CNAs from sequencing are not fully utilized due to immature analytical approaches. This proposal suggests continuing development and enhancement of analytical approaches for the detection of copy number variants and aberrations from sequencing data. Historically, the development of concepts, techniques, and methods in the basic sciences has been followed by their transition and use in applied areas. Specifically, advances in biology lead to applications in medicine. The developments we propose anticipate many forthcoming applications of whole genome sequencing in medicine, and set up a computational framework to power clinical care with tools for copy number variants discovery and analysis. 3

项目概要/摘要技术进步使个体基因组测序成为临床现实，部分基因组测序事实上，预计几年内全基因组测序已经应用于临床护理。测序将成为一种标准程序，可以发现所有类型的个人基因组变异从而极大地促进个体化医疗。然而，快速、可靠地分析此类数据具有挑战性；在发挥全基因组测序的临床潜力之前，需要对分析进行改进具体来说，拷贝数变异占人类遗传多样性的很大一部分。经常在癌症中观察到，并且与多种疾病、癌症易感性、癌症进展和侵袭性、个体对治疗的反应以及患者治疗后的生活质量（即，因此，对拷贝数变异进行全面的识别和分析将是可能的。帮助我们更全面地阐明它们对人类健康（特别是癌症）功能影响的生物学的出现和进展）并将促进临床诊断和治疗。然而，由于不成熟，通过测序检测 CNV/CNA 的能力尚未得到充分利用。该提案建议继续发展和加强分析方法。从测序数据中检测拷贝数变异和畸变的方法。历史上，基础科学的概念、技术和方法的发展其次是它们在应用领域的转变和使用，具体来说，生物学的进步导致了它们的应用。我们提出的发展预示着全基因组的许多即将到来的应用。医学测序，并建立一个计算框架，通过复制工具为临床护理提供支持数字变异的发现和分析。 3