Bioinformatics Core
生物信息学核心
基本信息
- 批准号:10614011
- 负责人:
- 金额:$ 11.91万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-05-01 至 2027-04-30
- 项目状态:未结题
- 来源:
- 关键词:AccelerationAnatomyBindingBioinformaticsBiologicalBiological AssayCell LineageClinicalCytometryDNADataData SetDevelopmentDrug or chemical Tissue DistributionEnsureEvaluationGenbankGene ExpressionGenetic Sequence DatabasesGenetic TranscriptionHIVImmunologicsImmunophenotypingInflammatoryInterruptionKnowledge DiscoveryLinkMeasuresMethodsMolecularNaturePathogenesisPerformancePlayProceduresProteomicsProvirusesRecrudescencesResearch PersonnelResolutionRoleSamplingSeasonsSequence Read ArchiveTechnologyTimeTissuesTranscriptUnited States National Institutes of HealthValidationViralantiretroviral therapyclinically relevantcomplex datadata managementdata submissiondigitalexperienceexperimental studyhigh dimensionalityin vivoinsightlearning strategymachine learning algorithmmachine learning methodmultidimensional datanano-stringpotential biomarkerpredictive signaturepublic repositoryrelational databaserepositorysingle-cell RNA sequencingtheoriestranscriptomicsviral RNAviral reboundvirus genetics
项目摘要
PROJECT SUMMARY/ABSTRACT (Bioinformatics Core)
The development, evaluation and implementation of HIV cure strategies will depend critically on our
understanding of the “rebound-competent” HIV reservoir, and our capacity to determine when this reservoir is
reduced to the point that viral recrudescence is unlikely in the near-term, justifying cessation of antiretroviral
therapy (ART). Increasing evidence suggests that the active HIV reservoir during ART likely contributes to
viral recrudescence following ART interruption, and the nature of HIV expression varies dramatically in vivo
with respect to time, anatomic compartment, and target cell lineage. In this P01, several cutting-edge, high-
dimensional technologies will be applied to a broad range of clinical samples to characterize diverse, active
HIV reservoir subsets and their immunological and inflammatory impact in unprecedented detail. These
technologies include: HIV transcription profiling, the intact proviral DNA assay (IPDA), intact viral RNA assay
(IVRA), single provirus and HIV transcript sequencing, single-cell RNA-seq (scRNA-seq), Cytometry by time of
flight (CyTOF), and nanoString GeoMX digital spatial profiling (DSP) generating high-resolution transcriptomic
and proteomic data from tissues.
Our massive and complex datasets will require extensive and sophisticated data management, integration, and
bioinformatic and biostatical analyses to ensure that clinically relevant biological insights are distilled from our
experiments. The Bioinformatics Core, staffed by seasoned investigators with specific expertise in the analysis
of high-dimensional data to study HIV pathogenesis and persistence, will perform these critical functions within
our P01 project.
We will pursue three Specific Aims in the Bioinformatics Core: In Aim 1, we will compile, curate, and
disseminate data generated by all three P01 projects, building a searchable, relational database for our
investigative team and submitting data to relevant public repositories to maximize data accessibility. In Aim 2,
we will apply ensemble machine learning methods to high-dimensional data generated in all three P01 projects
to identify molecular and immunologic signatures of diverse active HIV reservoir subsets. In Aim 3, we will
apply advanced knowledge discovery methods to data generated from analytical treatment interruption (ATI)
samples (Project #3) to reveal predictors and HIV reservoir signatures of viral rebound following ART
cessation.
The Bioinformatics Core will play a central role in ensuring successful implementation of our P01 objectives to
advance the HIV cure agenda.
项目总结/摘要(生物信息学核心)
艾滋病毒治疗战略的制定、评估和实施将主要取决于我们的
了解“反弹能力”的艾滋病毒水库,以及我们确定何时这个水库是
减少到病毒在短期内不太可能复发的程度,证明停止抗逆转录病毒治疗是合理的
治疗(ART)。越来越多的证据表明,ART期间活跃的HIV库可能有助于
ART中断后病毒复发,HIV表达的性质在体内变化很大
关于时间、解剖区室和靶细胞谱系。在这P01,几个尖端,高-
三维技术将应用于广泛的临床样本,以表征不同的,活跃的,
艾滋病病毒库亚群及其免疫和炎症影响的前所未有的细节。这些
技术包括:HIV转录谱分析、完整前病毒DNA检测(IPDA)、完整病毒RNA检测
(IVRA),单原病毒和HIV转录物测序,单细胞RNA-seq(scRNA-seq),
飞行(CyTOF)和nanoString GeoMX数字空间分析(DSP)生成高分辨率转录组学
和组织中的蛋白质组数据。
我们庞大而复杂的数据集将需要广泛而复杂的数据管理、集成和
生物信息学和生物统计学分析,以确保从我们的
实验生物信息学核心,由经验丰富的研究人员组成,具有分析方面的特定专业知识
研究艾滋病毒发病机制和持久性的高维数据,将在
我们的P01项目
我们将在生物信息学核心中追求三个具体目标:在目标1中,我们将编译,策划,
传播所有三个P01项目产生的数据,为我们的
调查小组和向相关公共储存库提交数据,以最大限度地提高数据的可访问性。在目标2中,
我们将把集成机器学习方法应用于所有三个P01项目中生成的高维数据
以确定不同的活性HIV储库亚群的分子和免疫学特征。在目标3中,我们
将先进的知识发现方法应用于分析治疗中断(ATI)生成的数据
样本(项目#3),以揭示ART后病毒反弹的预测因子和HIV储库特征
停止
生物信息学核心将在确保成功实施我们的P01目标方面发挥核心作用,
推动艾滋病治愈议程。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Satish Kumar Pillai其他文献
Satish Kumar Pillai的其他文献
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{{ truncateString('Satish Kumar Pillai', 18)}}的其他基金
Innate Sensing of Cell-Free DNA and the Interferon-Mediated Control of HIV In Vivo
无细胞 DNA 的先天感知和体内干扰素介导的 HIV 控制
- 批准号:
10620085 - 财政年份:2023
- 资助金额:
$ 11.91万 - 项目类别:
Innate Sensing of Cell-Free DNA and the Interferon-Mediated Control of HIV In Vivo
无细胞 DNA 的先天感知和体内干扰素介导的 HIV 控制
- 批准号:
10661305 - 财政年份:2022
- 资助金额:
$ 11.91万 - 项目类别:
Project 3: Identifying plasma biomarkers predicting time to HIV rebound after treatment interruption
项目 3:识别血浆生物标志物,预测治疗中断后 HIV 反弹的时间
- 批准号:
10223997 - 财政年份:2017
- 资助金额:
$ 11.91万 - 项目类别:
Effects of Cell-Intrinsic Immunity on Establishment and Reversal of HIV Latency
细胞内在免疫对 HIV 潜伏期建立和逆转的影响
- 批准号:
9354580 - 财政年份:2015
- 资助金额:
$ 11.91万 - 项目类别:
Effects of Cell-Intrinsic Immunity on Establishment and Reversal of HIV Latency
细胞内在免疫对 HIV 潜伏期建立和逆转的影响
- 批准号:
9134183 - 财政年份:2015
- 资助金额:
$ 11.91万 - 项目类别:
High throughput measurement of envelope gene diversity for an HIV incidence assay
用于 HIV 发病率测定的包膜基因多样性的高通量测量
- 批准号:
8720184 - 财政年份:2013
- 资助金额:
$ 11.91万 - 项目类别:
High throughput measurement of envelope gene diversity for an HIV incidence assay
用于 HIV 发病率测定的包膜基因多样性的高通量测量
- 批准号:
8466485 - 财政年份:2013
- 资助金额:
$ 11.91万 - 项目类别:
High throughput measurement of envelope gene diversity for an HIV incidence assay
用于 HIV 发病率测定的包膜基因多样性的高通量测量
- 批准号:
8717846 - 财政年份:2013
- 资助金额:
$ 11.91万 - 项目类别:
Characterization of the HIV-1 Latent Reservoir in CCR5-Delta 32 Heterozygotes
CCR5-Delta 32 杂合子中 HIV-1 潜伏库的表征
- 批准号:
8603539 - 财政年份:2013
- 资助金额:
$ 11.91万 - 项目类别:
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