Combinatorial and graph theoretical approach to systems biology and mol. evo.

系统生物学和分子生物学的组合和图论方法。

• 批准号: 8943247
• 负责人: Teresa Przytycka
• 金额: $ 143.5万
• 依托单位: NATIONAL LIBRARY OF MEDICINE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8943247
• 关键词: Algorithmic Software; Algorithms; Binding; Biological; Cancer Model; Cells; Cloud Computing; Collaborations; Complex; Computational Biology; Computer Analysis; Computer software; Computing Methodologies; DNA; DNA Structure; Data; Data Analyses; Dependency; Development; Disease; Elements; Evolution; Gene Dosage; Gene Expression; Gene Expression Regulation; Genes; Genetic; Genetic Transcription; Genetic Variation; Genotype; Graph; Growth Factor Gene; Human Genome Project; Imagery; Language; Lead; Malignant Neoplasms; Methods; Mind; Modeling; Molecular; Mutation; Noise; Nucleotides; Oral; Paper; Phenotype; Play; Preparation; Process; Property; RNA; Regulatory Element; Reporting; Role; Signal Transduction; Speed; Structure; System; Systems Biology; Technology; The Cancer Genome Atlas; Variant; Work; aptamer; base; biological systems; combinatorial; design; fly; gene function; graphical user interface; insight; mathematical model; parallel processing; response; symposium; theories; tool; trait

My group continued to work on computational methods to study the dynamics of biological networks, impact of genetic variations and structural variation on gene expression, organismal phenotype in the context of complex diseases, analysis of new high throughput experimental data, and developing methods for analysis of HT-SELEX data. We are developing a comprehensive software package, AptaTools, for analysis of HT-SELEX data. Aiming at providing a comprehensive HT-SELEX data-analysis software. AptaTools is designed with computational speed in mind and capable of simultaneously processing many selection cycles due to its parallel processing capabilities. It is hence suitable for cloud computing and deployment. Finally, a graphical user interface, AptaGUI, allows for efficient and dynamic visualization of the analysis. We expect, that this toolbox will become an indispensable tool for guiding the selection of aptamers as well as for uncovering further general properties of the selection process and ultimately lead to a better utilization of HT-SELEX results. As part of this package, we have developed new clustering algorithm, AptaCluster which is, up to our best knowledge, the only currently available tool capable of efficiently clustering entire aptamer pools of more than 20 Million sequences. The paper describing this algorithm has been accepted for oral presentation at RECOMB 2014 - a pioneer conference in Computational Biology (1). We also continued to work on methods to delineate genetic underpinnings of complex traits. Following the development of our two new methods, Module Cover, and the probabilistic cancer model reported last year, we are working on combining the two methods and applying the combined approach to study TCGA PanCancer data. We also continued the collaboration with Brian Oliver's group on gene regulation and on modeling of the impact of gene copy number of fly phenotype. In this study we use DrosDel fly panel. Flies in this panels have deletions of various chromosomal regions making some of the genes to have a single copy. This main work is still under progress. We contributed to the related paper (2). Continuing a successful collaboration with David Levens we continue our work on the impact of transcription induced supercoiling on gene regulation and formation of non-B-DNA structures (3). A paper reporting the results of this study in the context of non-B-DNA structures is under preparation. Focusing on more computational analysis, we leveraged 1000 human genome project analyzed the impact of nucleotide variations. The paper describing these results is under revision. Finally, we continue to support other groups by providing computational expertise for their studies (4-6).

我的小组继续研究计算方法来研究生物网络的动态，遗传变异和结构变异对基因表达的影响，复杂疾病背景下的生物表型，新的高通量实验数据的分析，以及开发HT-SELEX数据分析方法。 我们正在开发一个全面的软件包，AptaTools，用于分析HT-SELEX数据。旨在提供一个全面的HT-SELEX数据分析软件。AptaTools的设计考虑到了计算速度，并且由于其并行处理能力，能够同时处理许多选择周期。因此，它适合云计算和部署。最后，一个图形用户界面，AptaGUI，允许分析的有效和动态的可视化。我们期望，这个工具箱将成为一个不可或缺的工具，用于指导适体的选择以及揭示选择过程的进一步一般特性，并最终导致更好地利用HT-SELEX结果。 作为该软件包的一部分，我们开发了新的聚类算法AptaCluster，据我们所知，这是目前唯一能够有效聚类超过2000万个序列的整个适体池的工具。描述该算法的论文已被接受为RECOMB 2014的口头报告-计算生物学的先驱会议（1）。 我们还继续研究描绘复杂性状遗传基础的方法。 在我们的两种新方法模块覆盖和去年报道的概率癌症模型的开发之后，我们正在努力将这两种方法结合起来，并将组合方法应用于研究TCGA PanCancer数据。 我们还继续与Brian奥利弗的小组在基因调控和果蝇表型基因拷贝数影响的建模方面进行合作。 在本研究中，我们使用DrosDel飞面板。图中的果蝇具有多个染色体区域的缺失，使得一些基因具有单拷贝。 这项主要工作仍在进行中。我们为相关论文做出了贡献（2）。 继续与大卫莱文斯的成功合作，我们继续我们的工作，转录诱导的超螺旋对基因调控和非B-DNA结构的形成的影响（3）。 目前正在编写一份报告，在非B-DNA结构的背景下报告这项研究的结果。 重点是更多的计算分析，我们利用1000个人类基因组计划分析了核苷酸变异的影响。描述这些结果的文件正在修订中。 最后，我们继续支持其他团体，为他们的研究提供计算专业知识（4 - 6）。