Data Analysis Tools for Emerging High-Throughput Technologies

适用于新兴高通量技术的数据分析工具

• 批准号: 10612937
• 负责人: Rafael Angel Irizarry
• 金额: $ 59.68万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10612937
• 关键词: Adoption; Affect; Algorithms; Basic Science; Biological; Biomedical Research; Computer software; DNA Methylation; DNA Sequence; Data; Data Analyses; Data Analytics; Data Set; Database Management Systems; Development; Disease; FarGo; Gene Expression; Goals; Investigation; Laboratories; Measurement; Measures; Methodology; Molecular; National Research Council; Nucleic Acids; Outcome; Phenotype; Protocols documentation; Province; Publications; Research Personnel; Sampling; Scanning; Signal Transduction; Source; Statistical Methods; Systematic Bias; Techniques; Technology; Translational Research; Variant; Work; clinical application; complex data; flexibility; frontier; high throughput technology; improved; indexing; interest; precision medicine; success; tool

Project Summary Biomedical research and the basic sciences are increasingly dependent on high-throughput technologies that have the ability to simultaneously measure thousands of nucleic acid molecules in a sample. In combination with ingenious laboratory protocols, these technologies have permitted unprecedented ways of studying the molecular basis of disease and phenotypic variation. As a result of the increasing adoption of these technologies, more investigations rely on complex datasets and require the development of new statistical techniques to adequately interpret data. Today, high-throughput technologies applications go far beyond their original task of studying DNA sequence itself and also include the measurement of quantitative and dynamic outcomes such as gene expression levels and DNA methylation (DNAm) status. These quantitative and dynamic outcomes introduce levels of variability that give rise to further data analytic challenges related to distinguishing unwanted sources of variability from bio- logically relevant signals. Furthermore, when measuring these quantitative outcomes, data are subject to severe technological and biological biases that can substantially impact downstream analyses. Our group has previously demonstrated that statistical methodology can provide great improvements over ad-hoc algorithms offered as de- faults by technology developers. Our highly cited statistical methodology and our widely used software demonstrate the success of our work. The National Research Council's Frontiers in Massive Data Analysis publication states that, “the challenges for massive data go beyond the storage, indexing, and querying that have been the province of classical database systems and instead hinge on the ambitious goal of inference”. Inference is particularly relevant in biomedical applications since we often look to draw conclusions based on observed differences between groups in the presence of within group variability. Two particularly challenging tasks relate to performing valid inference when 1) we perform scans over large spaces to identify small regions of interests and 2) the data is affected by unexpected systematic bias or batch effects. We will focus on these two general challenges. Our specific proposal is to work on the most urgent needs of researchers facing new challenges as they increasingly rely on high-throughput techniques. We will leverage the expertise of our collaborators to prioritize projects. We greatly appreciate the flexibility permitted by the R35 mechanism as it will help us maximize the impact of our work.

项目概要 生物医学研究和基础科学越来越依赖于高通量技术 结合巧妙的技术，能够同时测量样品中的数千个核酸分子。 实验室协议，这些技术提供了前所未有的方法来研究分子基础 由于这些技术的日益采用，需要进行更多的研究。 依赖复杂的数据集，需要开发新的统计技术来充分解释数据。 如今，高通量技术的应用远远超出了研究 DNA 序列的最初任务 本身还包括定量和动态结果的测量，例如基因表达水平和 DNA 甲基化 (DNAm) 状态这些定量和动态结果引入了可变性水平。 引起进一步的数据分析挑战，这些挑战与区分不需要的变异来源和生物变异有关。 此外，在测量这些定量结果时，数据会受到严格的影响。 我们的团队之前曾发现过可能严重影响下游分析的技术和生物学偏差。 统计方法可以提供比作为 de-hoc 算法提供的巨大改进。 我们被广泛引用的统计方法和广泛使用的软件证明了技术开发人员的错误。 我们工作的成功。 国家研究委员会的《海量数据分析前沿》出版物指出，“挑战 对于海量数据，超越了传统数据库的存储、索引和查询范围 系统，而是取决于推理的雄心勃勃的目标”，推理在生物医学中尤其重要。 应用程序，因为我们经常希望根据存在的组之间观察到的差异得出结论 组内变异性的两个特别具有挑战性的任务与执行有效推理有关：1）我们 对大空间进行扫描以识别小的兴趣点，2）数据受到意外的影响 我们将重点关注这两个一般性挑战。 随着越来越多地依赖高通量技术，研究人员面临新挑战的最迫切需求。 我们将利用合作者的专业知识来确定项目的优先顺序，我们非常欣赏这种灵活性。 R35 机制允许，因为它将帮助我们最大限度地发挥我们工作的影响。

项目成果

Discovery of antibodies and cognate surface targets for ovarian cancer by surface profiling.

• DOI: 10.1073/pnas.2206751120
• 发表时间: 2023-01-03
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1

Detection of renal cell carcinoma using plasma and urine cell-free DNA methylomes.

• DOI: 10.1038/s41591-020-0933-1
• 发表时间: 2020-07
• 期刊: Nature medicine
• 影响因子: 82.9
• 作者: Nuzzo PV;Berchuck JE;Korthauer K;Spisak S;Nassar AH;Abou Alaiwi S;Chakravarthy A;Shen SY;Bakouny Z;Boccardo F;Steinharter J;Bouchard G;Curran CR;Pan W;Baca SC;Seo JH;Lee GM;Michaelson MD;Chang SL;Waikar SS;Sonpavde G;Irizarry RA;Pomerantz M;De Carvalho DD;Choueiri TK;Freedman ML
• 通讯作者: Freedman ML

Effectiveness estimates of three COVID-19 vaccines based on observational data from Puerto Rico.

• DOI: 10.1016/j.lana.2022.100212
• 发表时间: 2022-05
• 期刊: Lancet regional health. Americas
• 作者: Robles-Fontán MM;Nieves EG;Cardona-Gerena I;Irizarry RA
• 通讯作者: Irizarry RA

All-cause excess mortality across 90 municipalities in Gujarat, India, during the COVID-19 pandemic (March 2020-April 2021).

• DOI: 10.1371/journal.pgph.0000824
• 发表时间: 2022
• 期刊: PLOS global public health

Differential richness inference for 16S rRNA marker gene surveys.

• DOI: 10.1186/s13059-022-02722-x
• 发表时间: 2022-08-01
• 期刊: Genome biology
• 影响因子: 12.3