Statistical Methods for Analysis of Tumor Heterogeneity in Genetic Epidemiology
遗传流行病学中肿瘤异质性分析的统计方法
基本信息
- 批准号:10656385
- 负责人:
- 金额:$ 40.76万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-07-01 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:AccountingAddressAlgorithmsAntineoplastic AgentsBioconductorBioinformaticsCandidate Disease GeneClinicalColorectal CancerCommon NeoplasmCommunitiesDNADNA RepairDNA biosynthesisDataDevelopmentDiseaseEnvironmentEnvironmental Risk FactorEpidemiologyEtiologyEventFundingGenesGeneticGenetic VariationGerm-Line MutationGoalsGrantHarvestIndividualLeadLinkLinkage DisequilibriumMalignant NeoplasmsMethodsMismatch RepairMorbidity - disease rateMutationNormal CellOutcomeParaffin EmbeddingPathway interactionsPatientsPlayPoint MutationResearch PersonnelRiskRisk FactorsRoleSample SizeSamplingSiteSmokingSomatic MutationStatistical Data InterpretationStatistical MethodsTechnologyTestingUncertaintyVariantcancer epidemiologycancer genomecancer preventioncancer riskcancer sitecancer therapycostgene discoverygene repairgenetic associationgenetic epidemiologygenetic risk factorgenetic variantgenome wide association studygenome-wideimprovedinsightinterestmethod developmentmortalityneoplastic cellnovelresponsescreeningstatisticstumortumor heterogeneitytumor progressiontumorigenesisuser friendly software
项目摘要
PROJECT SUMMARY/ABSTRACT
Cancer is a major morbidity and mortality burden throughout the world. While much progress has been
made, the elimination of cancer has not yet been achieved. In the currently funded grant, we have developed
statistical methods for genome-wide association analysis of cancer and studied cancer by the site of origin.
However, even within a site, cancer can have distinct mutational profiles across patients. Pooling all cancer
cases occurring at one site as one disease may miss important clinical and etiological insights. Recently
technology advances have made it possible to characterize somatic mutations at great detail in large numbers
of tumors, providing a unique opportunity to study tumor heterogeneity. The objective of this competitive
renewal is to continue our statistical methods development for association analyses of tumor heterogeneity
with clinical outcomes, and for studying the underlying genetic and environmental etiology.
There are challenges in analyzing the somatic mutation data. First, somatic mutation may only exist in a
subset of tumor cells of a patient, so called intra-tumor heterogeneity. While our application is focused on
tumor heterogeneity across patients, because intra-tumor heterogeneity can also impact clinical outcomes,
important insight could be missed if it were not accounted for. The goal of Aim 1 is to develop statistical
methods to account for intra-tumor heterogeneity when assessing the association of somatic mutations with
clinical outcomes. Second, it is of great interest to discover germline-somatic mutation link; however, despite
that tumor studies are considerably larger than before due to technology advances, the power for discovering
such links remains limited because of moderate genetic effects and the burden of accounting for multiple
comparison from testing millions of variants. The goal of Aim 2 is to develop novel screening strategies for
prioritizing genetic variants in testing genome-wide association with tumor heterogeneity. We will achieve
optimal power by using the weighted hypothesis testing framework, allowing for correlated genetic variants and
continuous screening statistics. Third, it is common that tumor blocks can usually only be retrieved from a
subset of cases and tumor sequencing data are thus only available for this subset. Meanwhile, extensive risk
factor information has already been collected for the larger study. The goal of Aim 3 is to develop a robust and
efficient approach to incorporate the summary statistics information from the larger study for characterizing the
effects of genetic and environmental risk factors on risk of developing cancer with specific tumor feature.
The methods will be applied to the Genetics and Epidemiology of Colorectal Cancer Consortium
(GECCO, PI: Ulrike Peters; Lead Biostatistician: Li Hsu), which includes over 125,000 colorectal cancer cases
and controls all with GWAS data and additionally 7,000 tumors sequencing data. As our methods are also
applicable to other cancer studies, we will implement them in computationally efficient and user-friendly
software packages and disseminate them to the community through R/CRAN, R/Bioconductor, or Github.
项目摘要/摘要
癌症是全世界的主要发病率和死亡率负担。虽然进展很大
制作,尚未消除癌症。在当前资助的赠款中,我们已经开发了
基因组全基因组关联分析的统计方法,对原产地点研究了癌症。
但是,即使在一个站点内,癌症也可以在患者之间具有不同的突变特征。汇集所有癌症
在一个部位发生的病例可能会错过重要的临床和病因见解。最近
技术的进步使得大量详细详细描述体细胞突变成为可能
肿瘤,为研究肿瘤异质性提供了独特的机会。这个竞争激烈的目标
更新将继续我们的统计方法开发以进行肿瘤异质性的关联分析
具有临床结果,并用于研究潜在的遗传和环境病因。
分析体突变数据存在挑战。首先,体细胞突变可能仅存在于
患者的肿瘤细胞子集,所谓的肿瘤内异质性。而我们的应用集中于
患者的肿瘤异质性,因为肿瘤内异质性也会影响临床结果,所以
如果不考虑重要的洞察力,可能会错过。目标1的目标是开发统计
评估体细胞突变与
临床结果。其次,发现种系及其性突变链接是引起极大的兴趣。但是,尽管如此
由于技术进步,肿瘤研究比以前大得多,这是发现的力量
由于遗传效应中等和计算多个的负担,此类联系仍然受到限制
测试数百万变体的比较。目标2的目标是制定新颖的筛选策略
优先在测试全基因组与肿瘤异质性结合的遗传变异方面的优先级。我们将实现
通过使用加权假设检验框架,最佳功率,允许相关的遗传变异和
连续筛选统计。第三,通常只能从一个
因此,病例和肿瘤测序数据的子集仅适用于该子集。同时,风险很大
已经为大型研究收集了因素信息。 AIM 3的目标是开发一个健壮的和
有效地纳入较大研究的摘要统计信息以表征的有效方法
遗传和环境风险因素对具有特定肿瘤特征发展癌症风险的影响。
该方法将应用于结直肠癌联盟的遗传学和流行病学
(Gecco,PI:Ulrike Peters;首席生物统计学家:Li HSU),其中包括超过125,000个结直肠癌病例
并用GWAS数据控制所有内容,并另外7,000个肿瘤测序数据。因为我们的方法也是
适用于其他癌症研究,我们将在计算高效且用户友好的情况下实施它们
软件包并通过R/Cran,R/Bioconductor或GitHub将它们传播到社区。
项目成果
期刊论文数量(7)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Robust functional principal component analysis via a functional pairwise spatial sign operator.
通过函数成对空间符号算子进行稳健的函数主成分分析。
- DOI:10.1111/biom.13695
- 发表时间:2023
- 期刊:
- 影响因子:1.9
- 作者:Wang,Guangxing;Liu,Sisheng;Han,Fang;Di,Chong-Zhi
- 通讯作者:Di,Chong-Zhi
Adjusted time-varying population attributable hazard in case-control studies.
病例对照研究中调整后随时间变化的人群归因危险。
- DOI:10.1177/0962280219831725
- 发表时间:2020
- 期刊:
- 影响因子:2.3
- 作者:Zhao,Wei;Zheng,Jiayin;Chen,YingQing;Hsu,Li
- 通讯作者:Hsu,Li
Space-log: a novel approach to inferring gene-gene net-works using SPACE model with log penalty.
- DOI:10.12688/f1000research.26128.2
- 发表时间:2020
- 期刊:
- 影响因子:0
- 作者:Wu QV;Sun W;Hsu L
- 通讯作者:Hsu L
A Generalized Integration Approach to Association Analysis with Multi-category Outcome: An Application to a Tumor Sequencing Study of Colorectal Cancer and Smoking.
多类别结果关联分析的通用整合方法:在结直肠癌和吸烟的肿瘤测序研究中的应用。
- DOI:10.1080/01621459.2022.2105703
- 发表时间:2023
- 期刊:
- 影响因子:3.7
- 作者:Zheng,Jiayin;Dong,Xinyuan;Newton,ChristinaC;Hsu,Li
- 通讯作者:Hsu,Li
Multivariate association analysis with somatic mutation data.
- DOI:10.1111/biom.12745
- 发表时间:2018-03
- 期刊:
- 影响因子:1.9
- 作者:He Q;Liu Y;Peters U;Hsu L
- 通讯作者:Hsu L
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Li Hsu其他文献
Li Hsu的其他文献
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{{ truncateString('Li Hsu', 18)}}的其他基金
Statistical Methods for Inferring Gene-Phenotype Associations Using Omic Data from Gene Knockout and Human Phenotype Studies
使用基因敲除和人类表型研究的组学数据推断基因表型关联的统计方法
- 批准号:
10733165 - 财政年份:2023
- 资助金额:
$ 40.76万 - 项目类别:
Integrative Genomics into Genetic Association Studies of Blood Pressure and Stroke in African Americans
将基因组学整合到非裔美国人血压和中风的遗传关联研究中
- 批准号:
10372063 - 财政年份:2022
- 资助金额:
$ 40.76万 - 项目类别:
Integrative Genomics into Genetic Association Studies of Blood Pressure and Stroke in African Americans
将基因组学整合到非裔美国人血压和中风的遗传关联研究中
- 批准号:
10656163 - 财政年份:2022
- 资助金额:
$ 40.76万 - 项目类别:
Statistical Methods for Analysis of Tumor Heterogeneity in Genetic Epidemiology
遗传流行病学中肿瘤异质性分析的统计方法
- 批准号:
9817026 - 财政年份:2015
- 资助金额:
$ 40.76万 - 项目类别:
Statistical Methods for Analysis of Tumor Heterogeneity in Genetic Epidemiology
遗传流行病学中肿瘤异质性分析的统计方法
- 批准号:
10432024 - 财政年份:2015
- 资助金额:
$ 40.76万 - 项目类别:
Methods for Integrating Functional Data into Complex Disease Genetic Analyses
将功能数据整合到复杂疾病遗传分析中的方法
- 批准号:
9087202 - 财政年份:2015
- 资助金额:
$ 40.76万 - 项目类别:
Methods for Integrating Functional Data into Complex Disease Genetic Analyses
将功能数据整合到复杂疾病遗传分析中的方法
- 批准号:
9308935 - 财政年份:2015
- 资助金额:
$ 40.76万 - 项目类别:
Statistical Methods for Analysis of Tumor Heterogeneity in Genetic Epidemiology
遗传流行病学中肿瘤异质性分析的统计方法
- 批准号:
10602853 - 财政年份:2015
- 资助金额:
$ 40.76万 - 项目类别:
Statistical Methods for Genetic Epidemiology Studies
遗传流行病学研究的统计方法
- 批准号:
9027514 - 财政年份:2015
- 资助金额:
$ 40.76万 - 项目类别:
Statistical Methods for Analysis of Tumor Heterogeneity in Genetic Epidemiology
遗传流行病学中肿瘤异质性分析的统计方法
- 批准号:
10186707 - 财政年份:2015
- 资助金额:
$ 40.76万 - 项目类别:
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