Collaborative Research: MODULUS: A Novel Spatiotemporal Multifractal Analysis to Evaluate Genome Dynamics

目前，对于基因组信息如何转化为生物体表型，环境信号如何改变分子信息流，以及基因组信息的生物学层次组织如何在短时间和长时间内影响信息处理和基因组动力学，仍然存在不完整的理解。该项目整合了生物学和数学方法来模拟和研究基因组信息响应多尺度变化的机制。利用统计物理和分析方法，通常应用于表征非生物系统的分形特性，研究人员探索染色体组织、基因组活动和基因组进化之间复杂的相互依赖关系。这项工作的结果将进一步了解基因组-表型关系和时空交叉依赖控制真菌基因组结构。通过一个沉浸式的实验室交流项目，参与该项目的学生将在生物学和数学的交叉领域获得独特的跨学科培训体验。研究人员还将通过南加州大学的维特比夏季本科生研究经验（SURE）和堪萨斯州立大学的女孩研究我们的世界（GROW）项目与不同的学习者群体进行接触。我们迫切需要解码染色体组织、基因组活动和基因组进化之间复杂的相互依赖关系，并了解跨越多个时空尺度的生物过程所调节的基因组与表型之间的关系。跨学科的研究团队将使用多重分形分析、统计物理和微分几何来建模和识别描述染色质动力学的高维数据信息处理中的因果关系。该项目的主要研究目标包括：1)建立一个整合多维基因组信息的数学框架，以量化基因组结构的多尺度性质，并预测与时间和环境驱动的基因组调节相关的现象学后果；2)基因组组织变化和环境胁迫下遗传信息流的信息处理机制确定和多尺度表征；3)利用开发的数学框架，研究DNA变化是否纯粹是随机的，或者物理、化学和环境压力是否以及在多大程度上影响了高进化性基因组区域的形成。这个项目的结果将提供深入了解真菌和真核生物基因组的更广泛的组织原则。该奖项由分子和细胞生物科学部的系统和合成生物学以及数学科学部的数学生物学项目共同资助。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Currently there remains an incomplete understanding of how genomic information translates into organismal phenotypes, how environmental signals alter the flow of molecular information, and how biology's hierarchical organization of genomic information impacts information processing and genome dynamics over short and long-periods of time. This project integrates biological and mathematical methods to model and investigate mechanisms through which genomic information responds to change across multiple scales. Using statistical-physics and analytical methods typically applied to characterizing fractal-properties of non-biological systems, investigators explore the complex interdependency between chromosome organization, genome activity and genome evolution. Results of the work will further understanding of the genome-to-phenome relationship and spatiotemporal cross-dependencies governing the fungal genomic architecture. Through an immersive laboratory exchange program students participating in the project will receive a unique interdisciplinary training experience at the intersection of biology and mathematics. Investigators will also engage various cohorts of learners through the University of Southern California's Viterbi Summer Undergraduate Research Experience (SURE) and Kansas State University's Girls Researching Our World (GROW) programs. There is a great need to decode the complex interdependency between chromosome organization, genome activity and genome evolution and understand the genome-to-phenome relationships modulated by biological processes that span multiple spatial and temporal scales. The interdisciplinary team of investigators will use multi-fractal analysis, statistical physics and differential geometry to model and identify causal links in information processing across high-dimensional data describing chromatin dynamics. Key research objectives of the project include: 1) Development of a mathematical framework that integrates multidimensional genomic information in order to quantify the multi-scale nature of genome structure and predict the phenomenological consequences associated with temporally and environmentally driven genomic modulation; 2) Determination of the information processing machinery and multi-scale characterization of the flow of genetic information in concordance to changes in genome organization and environmental stress; 3) Using the mathematical framework developed, investigate whether DNA changes are purely random or if and to what extent physical, chemical and environmental stressors inform the formation of genomic regions of high evolvability. Outcomes of this project will provide insight into broader organizational principles of fungal and eukaryotic genomes. This award was co-funded by Systems and Synthetic Biology in the Division of Molecular and Cellular Biosciences and the Mathematical Biology Program of the Division of Mathematical Sciences.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.