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

项目摘要/摘要技术的进步使单个基因组测序临床现实，部分基因组已经在临床护理中使用的测序。实际上，可以预期在几年内整个基因组测序将是一个标准过程，将允许发现各种类型的个人基因组变体那是如此的个性化药物。但是，对此类数据的快速分析是挑战。在整个基因组测序的临床潜力可能是意识到的。特别是，拷贝数的变化是人类遗传多样性的很大比例，是经常在癌症中观察到，并且与多种疾病，癌症易感性，癌症有关进展和侵入性，对治疗的个人反应以及治疗后患者的生活质量（即副作用的出现）。因此，副本数变体的全面识别和分析将帮助我们更充分地阐明其功能对人类健康的作用的生物学（特别是对于癌症出现和进展），并将促进临床诊断和治疗。但是，由于未成熟而无法完全利用从测序中检测CNV/CNA的能力分析方法。该建议表明分析的持续发展和增强从测序数据中检测拷贝数变体和畸变的方法。从历史上看，基本科学中的概念，技术和方法的发展已经是其次是它们在应用区域的过渡和使用。具体而言，生物学的进步导致应用药品。我们提出的发展预测整个基因组的许多即将应用在医学上进行排序，并建立一个计算框架，以使用复制工具为临床护理供电数字变体发现和分析。 3