Reconstructing mechanisms of somatic variation in diverse cellular lineages
重建不同细胞谱系体细胞变异的机制
基本信息
- 批准号:10544726
- 负责人:
- 金额:$ 36.09万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-01-09 至 2024-12-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAlgorithmsAllelesBasic ScienceBiologyCancer ModelCancerousCell LineageCellsCohort StudiesComputational algorithmComputer ModelsComputing MethodologiesDataData AnalysesData ScienceData SourcesDefectDevelopmentDevelopmental ProcessDiagnosisDiseaseEngineeringFoundationsFrequenciesGenerationsGeneticGenetic VariationGenomeGenomicsGoalsGuidelinesHealthHumanHuman DevelopmentIndividualInfrastructureInheritedKnowledgeMalignant NeoplasmsMapsMathematicsMethodsMosaicismMutationNatural regenerationNatureNucleotidesOrganismPersonsPhylogenetic AnalysisPilot ProjectsPrecancerous ConditionsProcessProductivityRecording of previous eventsReproducibilityResearch DesignResourcesRoleScienceSingle Nucleotide PolymorphismSomatic MutationStatistical AlgorithmStatistical ModelsTechnologyTestingTimeTissuesTranslatingTreesUnmarried personVariantWorkcancer riskcomputerized toolsdesigndevelopmental diseaseexperienceexperimental studygenomic datagrasphuman diseasehuman tissueimprovedinformatics infrastructureinformatics toolmathematical algorithmmathematical modelneoplastic cellnext generationnovelnovel sequencing technologypremalignantreconstructionsimulationtheoriestooltumor
项目摘要
Project Summary
Genomic technologies have made it possible to reconstruct, with ever-growing scope and detail, the landscape
of genetic variations across individuals, tissues, and time. One consequence of this is a growing appreciation
for the importance of somatic genetic variation. Somatic variations, and the hypermutability defects that can
produce them, have been most extensively studied in the context of cancers, but they have relevance to a
variety of other disorders, both germline and sporadic, as well as value in basic research into development and
regeneration. Yet we are only beginning to understand the processes by which genetic variations accumulate
in cancers and a few well-defined precancerous conditions. We so far know little about how somatic variation
processes act in potentially cancerous but asymptomatic or in purely healthy tissues. Understanding somatic
variation more broadly is a crucial question for developing informed models of cancer risk, pursuing options to
identify and potentially treat cancers before they start, as well as for diagnosing and treating other illnesses
that arise from non-cancerous somatic hypermutability or spontaneous genetic mosaicism.
Experience reconstructing cell lineages in cancers provides the foundation for building comparable
methods for the broader landscape of somatic genetic variability across cancerous, pre-cancerous, and non-
cancerous tissues. One crucial lesson of cell lineage reconstruction in cancers is that doing reproducible
science, and planning the experimental data-generation studies needed to do so, requires first understanding
the data to be generated and the mathematical/statistical models and algorithms by which it will be analyzed.
The field of tumor phylogenetics has provided a groundwork of theory and tools for reconstructing cell lineages
in the presence of diverse somatic mutation processes that can be adapted to address the problem of
reconstructing somatic variation processes more broadly. It has also provided crucial experience into best
practices and pitfalls in designing variation studies, which will be needed to guide new large-scale experimental
studies into non-cancerous somatic variation. Mapping the full landscape of human somatic variation and the
mechanisms that produce it will be a large effort of numerous experimental and computational groups that will
not succeed without a clear grasp on the data science problems it entails.
The proposed work will help to build the informatics infrastructure needed for somatic variation study
through four specific aims intended to leverage decades of experience with reconstructing somatic evolutionary
histories in cancers. It will advance the state-of-the-art of tools for variant calling and cell lineage tracing to
handle diverse mechanisms of somatic structural variations (SVs), copy number aberrations (CNAs), and
single nucleotide variations (SNVs). It will use these methods via simulation study to assess data needs and
study designs for identifying diverse somatic variation mechanisms. Finally, it will apply them in a pilot study of
existing variation resources, both to validate their use in and beyond the cancer context and to perform novel
discovery of cancerous, non-cancerous, and pre-cancerous somatic variation mechanisms.
项目总结
项目成果
期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
A Clonal Evolution Simulator for Planning Somatic Evolution Studies.
用于规划体细胞进化研究的克隆进化模拟器。
- DOI:10.1089/cmb.2023.0086
- 发表时间:2023
- 期刊:
- 影响因子:0
- 作者:Srivatsa,Arjun;Lei,Haoyun;Schwartz,Russell
- 通讯作者:Schwartz,Russell
Marker selection strategies for circulating tumor DNA guided by phylogenetic inference.
系统发育推断指导下的循环肿瘤 DNA 标记选择策略。
- DOI:10.1101/2024.03.21.585352
- 发表时间:2024
- 期刊:
- 影响因子:0
- 作者:Fu,Xuecong;Luo,Zhicheng;Deng,Yueqian;LaFramboise,William;Bartlett,David;Schwartz,Russell
- 通讯作者:Schwartz,Russell
Reconstructing tumor clonal lineage trees incorporating single-nucleotide variants, copy number alterations and structural variations.
- DOI:10.1093/bioinformatics/btac253
- 发表时间:2022-06-24
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
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Russell S Schwartz其他文献
Network and Pathway Analysis of Cancer Susceptibility (A)
癌症易感性网络与通路分析(A)
- DOI:
- 发表时间:
2014 - 期刊:
- 影响因子:2
- 作者:
Nancy Guo;Russell S Schwartz;Jiang Qian;Peilin Jia;Youping Deng - 通讯作者:
Youping Deng
Russell S Schwartz的其他文献
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{{ truncateString('Russell S Schwartz', 18)}}的其他基金
Reconstructing mechanisms of somatic variation in diverse cellular lineages
重建不同细胞谱系体细胞变异的机制
- 批准号:
9895197 - 财政年份:2020
- 资助金额:
$ 36.09万 - 项目类别:
Reconstructing mechanisms of somatic variation in diverse cellular lineages
重建不同细胞谱系体细胞变异的机制
- 批准号:
10329961 - 财政年份:2020
- 资助金额:
$ 36.09万 - 项目类别:
Reconstructing mechanisms of somatic variation in diverse cellular lineages
重建不同细胞谱系体细胞变异的机制
- 批准号:
10083750 - 财政年份:2020
- 资助金额:
$ 36.09万 - 项目类别:
DECONVOLUTION OF CLONAL HETEROGENEITY FROM BULK AND SINGLE-CELL VARIATION DATA
从大量和单细胞变异数据中解卷积克隆异质性
- 批准号:
9308198 - 财政年份:2017
- 资助金额:
$ 36.09万 - 项目类别:
Inferring in vivo Capsid Assembly Kinetics from in vitro by Stochastic Simulation
通过随机模拟从体外推断体内衣壳组装动力学
- 批准号:
7874520 - 财政年份:2009
- 资助金额:
$ 36.09万 - 项目类别:
Heterogeneous Cancer Progression from Microarray Data
微阵列数据的异质性癌症进展
- 批准号:
7694533 - 财政年份:2009
- 资助金额:
$ 36.09万 - 项目类别:
Inferring in vivo Capsid Assembly Kinetics from in vitro by Stochastic Simulation
通过随机模拟从体外推断体内衣壳组装动力学
- 批准号:
8295001 - 财政年份:2009
- 资助金额:
$ 36.09万 - 项目类别:
Heterogeneous Cancer Progression from Microarray Data
微阵列数据的异质性癌症进展
- 批准号:
8259813 - 财政年份:2009
- 资助金额:
$ 36.09万 - 项目类别:
Heterogeneous Cancer Progression from Microarray Data
微阵列数据的异质性癌症进展
- 批准号:
8193113 - 财政年份:2009
- 资助金额:
$ 36.09万 - 项目类别:
Inferring in vivo Capsid Assembly Kinetics from in vitro by Stochastic Simulation
通过随机模拟从体外推断体内衣壳组装动力学
- 批准号:
8098132 - 财政年份:2009
- 资助金额:
$ 36.09万 - 项目类别:
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