OCG Data Coordinating Center

OCG数据协调中心

• 批准号: 10329758
• 负责人: LEONARD FREEDMAN
• 金额: $ 55.3万
• 依托单位: LEIDOS BIOMEDICAL RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-31 至 2021-08-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10329758
• 关键词: AIDS related cancer; Acquired Immunodeficiency Syndrome; Acute Lymphocytic Leukemia; Acute Myelocytic Leukemia; Automobile Driving; Bioinformatics; Biology; Burkitt Lymphoma; Child; Chromosomes; Clinical; Collaborations; Communities; DNA Sequence; DNA Sequence Alteration; Data; Data Coordinating Center; Data Display; Data Set; Detection; Development; Ethics; Event; Face; Family; Future; Gene Expression Profile; Genes; Genetic; Genome; Genomic approach; Genomics; Goals; HIV; HIV Seropositivity; Human; Incidence; Informatics; Infrastructure; Kidney Neoplasms; Lead; Maintenance; Malignant Childhood Neoplasm; Malignant Neoplasms; Malignant neoplasm of lung; Methodology; Methods; Methylation; Molecular; Molecular Abnormality; Molecular Target; Mutation; Nephroblastoma; Neuroblastoma; Non-Hodgkin' s Lymphoma; Pathway interactions; Patients; Prevalence; Prevention; Prognostic Marker; RNA Interference; Refractory; Research; Research Personnel; Resolution; Resources; Role; Sampling; Structure; System; Techniques; Therapeutic; Time; Tissue Banks; Translating; Translations; Tumor Biology; Validation; base; burden of illness; cancer diagnosis; cancer genome; cancer genomics; cancer therapy; cohort; data access; data portal; data sharing; diagnostic biomarker; effective therapy; exome sequencing; functional genomics; genome sequencing; high risk; high throughput screening; human tissue; innovation; insight; medulloblastoma; miRNA expression profiling; new technology; next generation sequencing; novel; novel strategies; novel therapeutic intervention; novel therapeutics; operation; osteosarcoma; precision medicine; programs; rare cancer; small molecule; therapeutic target; transcriptome sequencing; tumor; whole genome

This proposal proposes to continue operations and maintenance of the OCG (ocg.cancer.gov) Data Coordinating Center (DCC) to accept, QC, and display data and data types generated by the TARGET, CGCI, CTD2 and other cancer genomics and translation projects. The primary focus of the TARGET and CGCI Initiatives remain identifying genomic alterations that offer pathways to novel therapeutic interventions that may lead to more effective treatments for cancers. NCI-CBIIT provides informatics support for the OCG programs. The Therapeutically Applicable Research to Generate Effective Treatments (TARGET) Initiative focuses to rapidly identify potential therapeutic targets in childhood cancers so that new, more effective treatments can be developed in shorter time and ultimately bring new hope to children and their families who face the devastating burden of these diseases. The TARGET Initiative (is focused on identifying therapeutic targets as well as prognostic and diagnostic markers in multiple childhood cancers. The initiative includes the study of high-risk Acute Lymphoblastic Leukemia (ALL), neuroblastoma (NBL), high-risk and treatment refractory Acute Myeloid Leukemia (AML), osteosarcoma (OS), and kidney tumors (including high risk Wilms tumor). These cancers were the chosen for study because of their prevalence among children, the inadequacy of current treatment options, the ongoing NCI-supported efforts to molecularly characterize these cancers, and the availability of clinically annotated, high-quality human tissue collections that met TARGET's strict scientific, technical, and ethical requirements. In the coming year, TARGET will include validation cohorts and other studies. The Cancer Genome Characterization Initiative (CGCI) supports cutting-edge genomics research on rare cancers. Researchers develop and apply advanced sequencing and other genome-based methods to identify novel genetic abnormalities in tumors. The extensive genetic profiles generated by CGCI may inform better cancer diagnosis and treatment. CGCI is another OCG program. CGCI focuses Burkitt Lymphoma and HIV+ Tumor Molecular Characterization Project (HTMCP). Previous projects included early stage Lung Cancers, Medulloblastoma, and Non-Hodgkin Lymphoma. The goal of the Burkitt Lymphoma Genome Sequencing Project (BLGSP) is to explore potential genetic changes in patients with Burkitt lymphoma that could lead to better prevention, detection, and treatment of this rare and aggressive cancer. The OCG, along with the Office of HIV and AIDS Malignancies (OHAM), initiated the HTMCP to gain insight into the genetic events driving HIV-associated cancers and to determine why certain cancers, but not others, have higher incidences in HIV-positive patients. The data generated by these projects are stored at the DCC. Cancer Target Discovery and Development (CTD²) initiative bridges the gap between the enormous volumes of data generated by genomic characterization studies and the ability to use these data for the development of human cancer therapeutics. It specializes in computational and functional genomics approaches critical for translating next-generation sequencing data. The Cancer Target Discovery and Development (CTD2) initiative is a collaborative network of OCG-supported Centers. The program strives to functionally validate discoveries from large-scale genomic initiatives and advance them toward precision medicine through the efforts of the Centers and open access data sharing. Through cross-Network collaborations, CTD2 uses innovative bioinformatics and functional biology to: (1) mine data to find alterations that potentially influence tumor biology, (2) characterize the functional roles of candidate alterations in cancers, and (3) identify novel approaches that target causative alterations either directly or indirectly. Because CTD2 is a “community resource project all information in the Data Portal is openly available to the scientific community and can be accessed without restrictions. Project descriptions, datasets, and methodologies generated by the Centers are shared through the CTD2 Data Portal (i.e. the OCG Data Coordinating Center). OCG oversees other genomics and translation projects which may generate molecular data that will be stored in the DCC. The formats, file types etc. is ever changing and the DCC evolves as needed. It is expected that the infrastructure already developed and being developed will be useable for the OCG data generated. The research conducted by OCG programs is divided into three distinct yet tightly integrated components that together form a system for selecting new molecular targets for the development of novel therapies for these childhood cancers: • Genomic Characterization: Using high-resolution array-based methods a)determine differences in the patterns of gene expression in cancer samples and non-cancerous samples and b) genome changes to characterize genome structural changes that correlate with each cancer, such as chromosome region gains and losses, methylation changes etc. are integrated to provide a complete genomic "overview" of each cancer. • Sequencing: Up-to-date genetic sequencing techniques are used to "read" genes that have been identified to have altered expression and/or structural alterations to identify the specific cancer-related mutations in the DNA sequence. Additionally, new technologies to sequence the whole-genome, whole-exome, RNA-seq, and miRNA-seq have and will be employed. • Identification of Therapeutic Targets–For example, RNA interference (RNAi), small molecule high-throughput screens are used to identify and initially validate potential targets identified from the genomic characterization and re-sequencing efforts. In the future, other approaches may be added.

该建议的建议旨在继续操作和维护OCG（ocg.cancer.gov）数据协调中心（DCC），以接受QC，并显示目标，CGCI，CTD2和其他癌症基因组学和翻译项目产生的数据和数据类型。目标和CGCI倡议的主要重点仍然是确定基因组改变的，这些改变为新型治疗干预提供了途径，这可能会导致对癌症的更有效治疗。 NCI-CBIIT为OCG计划提供信息支持。治疗性适用的研究以生成有效的治疗（目标）倡议重点，以快速识别儿童期癌症中潜在的治疗靶标，以便可以在短时间内开发出新的，更有效的治疗方法，并最终为面对遭受灾难性疾病烧毁的儿童及其家人带来新的希望。 The TARGET Initiative (is focused on identifying therapy targets as well as prognostic and diagnostic markers in multiple childhood cancers. The initiative includes the study of high-risk Acute Lymphoblastic Leukemia (ALL), neuroblastoma (NBL), high-risk and treatment refractory Acute Myeloid Leukemia (AML), osteosarcoma (OS), and kidney tumors (including high risk Wilms肿瘤是为了研究，因为它们在儿童中的流行，目前的治疗方法不足。倡议（CGCI）支持稀有癌症的尖端基因组学研究。 CGCI产生的广泛遗传特征可能会为更好的癌症诊断和治疗提供信息。 CGCI是另一个OCG程序。 CGCI聚焦Burkitt淋巴瘤和HIV+肿瘤分子表征项目（HTMCP）。先前的项目包括早期肺癌，髓母细胞瘤和非霍奇金淋巴瘤。伯基特淋巴瘤基因组测序项目（BLGSP）的目标是探索伯基特淋巴瘤患者的潜在遗传变化，这可能会导致对这种罕见和侵略性癌症的预防，检测和治疗更好。 OCG与HIV和AIDS MALIGNANCYS（OHAM）一起发起了HTMCP，以深入了解驱动与HIV相关的癌症的遗传事件，并确定为什么某些癌症（而不是其他癌症）在HIV阳性患者中具有更高的疾病。这些项目生成的数据存储在DCC中。癌症目标发现与发育（CTD²）倡议弥合了基因组表征研究产生的大量数据与使用这些数据进行人类癌症治疗的能力之间的差距。它专门研究计算和功能基因组学方法对于翻译下一代测序数据至关重要。癌症目标发现与发展（CTD2）倡议是OCG支持的中心的协作网络。该计划致力于从大规模基因组计划中进行功能验证发现，并通过中心的努力和开放访问数据共享将其推进到精确的医学。通过跨网络的合作，CTD2使用创新的生物信息学和功能生物学来：（1）矿山数据以找到可能影响肿瘤生物学的变化，（2）表征癌症中候选候选变化的功能作用，（3）识别靶向关键改变的新颖方法。 Because CTD2 is a “community resource project all information in the Data Portal is openly available to the scientific community and can be accessed without restrictions. Project descriptions, datasets, and methodsologies generated by the Centers are shared through the CTD2 Data Portal (i.e. the OCG Data Coordinating Center). OCG oversees other genomics and translation projects which may generate molecular data that will be stored in the DCC. The formats,文件类型正在发生变化，DCC会根据需要进化。基因表达在癌症样本和非癌样本中的基因表达模式以及b）基因组变化，以表征与每个癌症相关的基因组结构变化，例如染色体区域的增长和损失，甲基化变化等被整合以提供完整的基因组“概述”概述“概述”•测序：识别构成的遗传学效果或已识别“识别”的“读取效果”，“读取效果”已识别“读取”效果。 DNA序列中的特定癌症相关突变。此外，还将使用新的技术来对整个基因组，全象征，RNA-Seq和miRNA-Seq进行测序。 •鉴定治疗靶标 - 例如，RNA干扰（RNAI），小分子高通量筛选用于识别并最初验证从基因组表征和重新测试工作中鉴定出的潜在靶标。将来，可能会添加其他方法。