Radiogenomics Framework for Non-Invasive Personalized Medicine

非侵入性个性化医疗的放射基因组学框架

• 批准号: 8837360
• 负责人: Olivier Gevaert
• 金额: $ 51.55万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-02-15 至 2019-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8837360
• 关键词: Accounting; Adult; Algorithms; Archives; Belief; Bioinformatics; Biological Markers; Biopsy; Brain Neoplasms; Cancer Patient; Clinical; Clinical Treatment; Communities; Comorbidity; DNA; DNA Methylation; DNA Sequence Alteration; DNA copy number; Data; Development; Disease; Drug Targeting; EGFR gene; Edema; Environment; Epidermal Growth Factor Receptor; Gene Expression; Gene Expression Profile; Genes; Genomics; Glioblastoma; Glioma; Goals; Heterogeneity; High-Throughput Nucleotide Sequencing; Human; Image; Individual; Institution; Internet; Investigation; Lead; Learning; Lesion; Link; Location; MGMT gene; Magnetic Resonance Imaging; Malignant Neoplasms; Maps; Medical Imaging; Methods; Methylation; Molecular; Molecular Profiling; Mutation; Necrosis; Needle biopsy procedure; Oncogenes; Operative Surgical Procedures; Outcome; Patient Care; Patients; Pattern; Pharmaceutical Preparations; Phenotype; Property; RNA; Radiogenomics; Research; Resources; Sampling; Technology; The Cancer Genome Atlas; Three-Dimensional Image; Tissues; Translating; Tumor Tissue; anticancer research; base; c-erbB-1 Proto-Oncogenes; cancer imaging; cancer site; clinical care; clinically relevant; cohort; empowered; imaging biomarker; in vivo; innovation; malignant breast neoplasm; oncology; operation; outcome forecast; personalized medicine; prognostic; programs; protein profiling; public health relevance; quantitative imaging; radiologist; response; tumor

DESCRIPTION (provided by applicant): Molecular profiles of tumors are nowadays used to determine prognosis and to guide therapy. For example the presence of a mutation in the EGFR gene will most likely lead to anti-EGFR therapy. Recently an image phenotype was discovered that acts as a biomarker of EGFR mutation. This is a precursor of the possibilities of a new emerging field called radiogenomics defined as directly linking imaging features to underlying molecular properties. Research in radiogenomics is rapidly gaining recognition as a powerful new field that has several promising applications, such as non-invasive molecular lesion assessment. When image surrogates can be identified that mirror relevant molecular aberrations (e.g. a mutation in the EGFR gene) they can be readily translated in clinical care. The value added by radiogenomics can be readily translated, as medical imaging is part of routine management in oncology. However, these early applications have not taken full advantage of the opportunities. First, they limit the correlation to either a handful of manually annotated image features and a pre-selected set of molecular parameters. Secondly, the initial applications are limited to a single omics by focusing on gene expression, without taking into account DNA mutations, DNA copy number changes or DNA methylation changes. We will develop a radiogenomics framework to identify non-invasive biomarkers mirroring relevant molecular tumor properties that impact treatment and clinical outcome of human brain tumors. Our objective is not to mimic a radiologist's expertise through computational means, but to empower radiologists and clinicians with new biomarkers. We will offer innovative new algorithms to represent medical images. Once such a representation is computed (e.g., in the form of a large data matrix), we will identify univariate and multivariate image signatures predictive of clinical outcome. Next, we will use sophisticated methods for integration with molecular data to interrogate different views of the data with respect to a clinically relevant outcome. The end result is a radiogenomics map where image signatures of molecular properties and tumor heterogeneity can be hypothesized and validated. We will have image signatures that are prognostic and image signatures reflecting actionable molecular properties of a tumor such as drug target activity or drug signatures.

描述(申请人提供)：肿瘤的分子图谱目前被用来确定预后和指导治疗。例如，EGFR基因突变的存在极有可能导致抗EGFR治疗。最近，一种图像表型被发现作为EGFR突变的生物标志物。这是一个名为放射基因组学的新兴领域的可能性的先驱，该领域的定义是将成像特征与潜在的分子特性直接联系起来。放射基因组学的研究正在迅速得到认可，成为一个强大的新领域，具有几个有前途的应用，如非侵入性分子损伤评估。当图像替代物可以被识别为镜像相关的分子异常(例如，EGFR基因的突变)时，它们就可以很容易地在临床护理中被翻译。放射基因组学所增加的价值可以很容易地转化，因为医学成像是肿瘤学常规管理的一部分。然而，这些早期的应用程序并没有充分利用机会。首先，他们将相关性限制在少数几个手动注释的图像特征和一组预先选择的分子参数上。其次，最初的应用局限于单一的组学，侧重于基因表达，而没有考虑DNA突变、DNA拷贝数变化或DNA甲基化变化。我们将开发一个放射基因组学框架，以确定反映相关分子肿瘤属性的非侵入性生物标志物，这些分子肿瘤属性影响人脑肿瘤的治疗和临床结果。我们的目标不是通过计算手段模仿放射科医生的专业知识，而是赋予放射科医生和临床医生新的生物标志物。我们将提供创新的新算法来表示医学图像。一旦这样的表示被计算出来(例如，以大型数据矩阵的形式)，我们将识别预测临床结果的单变量和多变量图像签名。接下来，我们将使用复杂的方法来整合分子数据，以询问关于临床相关结果的数据的不同观点。最终的结果是一张放射基因组学地图，其中分子特性和肿瘤异质性的图像签名可以被假设和验证。我们将拥有预测预后的图像签名和反映肿瘤可操作分子属性的图像签名，如药物靶标活性或药物签名。