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，以研究生物网络的动力学，遗传变异的影响以及结构变异对基因表达，在复杂疾病背景下的生物表型，新的高吞吐量实验数据的分析以及开发用于分析HT-核的数据的方法。 我们正在开发一个综合的软件包，Aptatools，以分析HT-SELEX数据。旨在提供全面的HT-SELEX数据分析软件。 Aptatools的设计考虑了计算速度，并且由于其并行处理功能，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，图形用户界面Aptagui允许对分析的有效和动态可视化。我们希望，该工具箱将成为指导适体选择以及发现选择过程的进一步一般属性的必不可少的工具，并最终导致更好地利用HT-SELEX结果。 作为此软件包的一部分，我们开发了新的聚类算法，即aptAcluster，据我们所知，这是唯一能够有效地将整个适合池的唯一可用的工具，该工具超过2000万个序列。描述该算法的论文已在2014年的Repomb上接受了口头表现 - 计算生物学的先驱会议（1）。 我们还继续致力于描述复杂性状的遗传基础的方法。 在开发了两种新方法，模块覆盖物和去年报道的概率癌症模型之后，我们正在努力将两种方法合并并应用合并的方法来研究TCGA Pancancer数据。 我们还继续与布莱恩·奥利弗（Brian Oliver）的基因调节小组的合作以及对蝇型表型基因拷贝数的影响进行建模。 在这项研究中，我们使用Drosdel飞行面板。该面板中的苍蝇具有各种染色体区域的缺失，使一些基因具有单个副本。 这项主要工作仍在进行中。我们为相关论文（2）做出了贡献。 继续与David Levens进行成功的合作，我们继续在转录引起的超螺旋对基因调节和非B-DNA结构的形成的影响方面继续进行工作（3）。 在非B-DNA结构的背景下报告了这项研究结果的论文正在制备中。 为了进行更多的计算分析，我们利用1000个人类基因组项目分析了核苷酸变化的影响。描述这些结果的论文正在修订中。 最后，我们继续通过为他们的研究提供计算专业知识来支持其他小组（4-6）。