Genome Sequencing in support of the Gabriella Miller Kids First Pediatric Research Program Supplement

基因组测序支持 Gabriella Miller Kids First 儿科研究计划补充

• 批准号: 10909622
• 负责人: Stacey Gabriel
• 金额: $ 112.93万
• 依托单位: BROAD INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-23 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10909622
• 关键词: Child; Childhood; Clinical Trials; Collection; Communities; Data; Data Set; Diagnostic; Disease; Elements; Ensure; Evaluation; Generations; Genetic; Genome; Genomics; Goals; Intuition; Investigation; Malignant Childhood Neoplasm; Output; Patients; Pediatric Research; Phenotype; Refractory; Research; Research Personnel; Sampling; United States National Institutes of Health; Work; cohort; data resource; exome; flexibility; gene discovery; genome resource; genome sequencing; interest; programs; transcriptome; transcriptome sequencing; tumor; whole genome

ABSTRACT We propose to continue to provide data generation and processing activities that will enrich a genomic data resource to propel pediatric disease research and in particular the Pediatric MATCH trial cohort covering matched diagnostic and refractory tumor samples. Key elements to a successful program will be the provision of high quality genome sequence data on well-phenotyped patients, the collection and accessibility of data to the research community in an intuitive manner, and the integration of genetic data with phenotypic information in the context of this program and comparison to other large data resources. We propose to continue as a Kids First Sequencing Center at the Broad Institute as we have done for the past seven years for the program and as we have also done in support of other large flagship NIH genome projects. With this supplement, we will bring to bear our expertise in our somatic product offerings. Our center brings the domain expertise in high throughput data generation, processing and analysis, and disease gene discovery required to meet the objectives of the Kids First Program and NCI's Childhood Cancer Data Initiative (CCDI). We will apply deep, high-quality whole genome sequencing data on selected samples. We will be flexible to work closely and accommodate the needs and interests of selected X01 Investigators. We are flexible to a mix of cohort types, whether they are tumor/normal pairs or quads. We will also work with X01 Investigators to generate whole exome data at 100X coverage on selected samples. Additionally for samples that need further investigation at the transcriptome level, we will generate RNASeq data using a pipeline developed for challenging samples. We will participate in the evaluation of these data types and their overall impact on discovery and scientific output of the program.

抽象的 我们建议继续提供数据生成和处理活动 将丰富基因组数据资源，以推动儿科疾病研究，特别是 儿科 MATCH 试验队列涵盖匹配的诊断性和难治性肿瘤 样品。项目成功的关键要素是提供高质量的 表型良好的患者的基因组序列数据、收集和可获取性 以直观的方式向研究界提供数据，以及遗传数据的整合 与该计划背景下的表型信息以及与其他大型项目的比较 数据资源。 我们建议继续作为布罗德研究所的儿童优先测序中心 我们在过去七年中为该计划所做的工作，正如我们在 支持其他大型旗舰 NIH 基因组项目。通过这个补充，我们将带来 承担我们在躯体产品方面的专业知识。我们中心带来域名 高通量数据生成、处理和分析以及疾病基因方面的专业知识 实现儿童优先计划和 NCI 童年目标所需的发现 癌症数据倡议（CCDI）。 我们将针对选定的对象应用深度、高质量的全基因组测序数据 样品。我们将灵活地密切合作并满足各方的需求和利益 选择了X01调查员。我们可以灵活地适应队列类型的混合，无论它们是 肿瘤/正常对或四边形。我们还将与 X01 调查员合作生成完整的 选定样本的外显子组数据覆盖率为 100 倍。另外对于需要的样品 在转录组水平上进一步研究，我们将使用 为具有挑战性的样品开发的管道。我们将参与这些评估 数据类型及其对程序的发现和科学输出的总体影响。

项目成果

Elucidation of de novo small insertion/deletion biology with parent-of-origin phasing.

通过亲本定相阐明从头小插入/缺失生物学。

• DOI: 10.1002/humu.23971
• 发表时间: 2020
• 期刊: Human mutation
• 影响因子: 3.9
• 作者: Seiden,AllisonH;Richter,Felix;Patel,Nihir;Rodriguez,OscarL;Deikus,Gintaras;Shah,Hardik;Smith,Melissa;Roberts,Amy;King,EileenC;Sebra,RobertP;Sharp,AndrewJ;Gelb,BruceD
• 通讯作者: Gelb,BruceD

ORE identifies extreme expression effects enriched for rare variants.

ORE 识别了稀有变异丰富的极端表达效应。

• DOI: 10.1093/bioinformatics/btz202
• 发表时间: 2019
• 期刊: Bioinformatics (Oxford, England)
• 作者: Richter,F;Hoffman,GE;Manheimer,KB;Patel,N;Sharp,AJ;McKean,D;Morton,SU;DePalma,S;Gorham,J;Kitaygorodksy,A;Porter,GA;Giardini,A;Shen,Y;Chung,WK;Seidman,JG;Seidman,CE;Schadt,EE;Gelb,BD
• 通讯作者: Gelb,BD