CAREER: Knowledge-driven Analytics, Model Uncertainty, and Experiment Design

高通量、高含量数据采集技术的进步，推动现代科学研究从传统的还原论转向以数据驱动为重点的复杂系统研究的建构论。然而，在大数据分析中仍然存在重大问题，特别是在数据驱动的研究结果的可重复性方面。为了使传统的科学研究方法在丰富数据的帮助下从还原论转向建构论，提出了一种用于高维网络系统预测和干预的综合贝叶斯框架。这将为将前所未有的大量异构数据以累积的方式转化为可重复的科学知识提供方法，并提供基于客观的不确定性量化和基于此的最佳实验设计的新概念。提出的知识驱动分析具有强大的潜力，可以将现有的各种大规模数据转化为可复制的知识，从而推动生命和材料科学研究。如果成功，它最终可以带来更有效的实验设计的计算工具，以最大限度地利用现有的大数据，并加快有效的疾病治疗和新材料发现的过程。该提案的跨学科性质有望通过研究和教育促进工程、生命科学和材料科学之间的思想交流。该提案的更广泛影响包括将拟议的研究与教育计划相结合：(1)加强与生命和材料科学合作者的互动。除了公开该项目的所有工具和研究成果外，开发的算法和工具，包括必要的技术帮助，将分发给合作者，以便更有效地合作；(2)开发工程、数学、生命和材料科学相结合的新课程，并将其纳入工程课程中，为各级学生的教育和研究培训提供帮助，帮助新一代研究人员为跨学科研究奠定广泛而坚实的基础，并为他们应对现实挑战做好必要的技能准备。这些课程将在校园内开设，以吸引对科学和工程研究感兴趣的女性和少数族裔学生；(3)让本科生和研究生参与跨学科领域的研究，通过与REU项目和其他旨在增加德克萨斯农工大学（TAMU）多样性的奖学金项目的合作，努力增加未被充分代表的科学和工程群体的参与。该建议的科学重点是解决存在于高维网络系统的不确定模型预测和干预中的数学和计算问题。以下开放问题将被解决：(1)开发基于网络的贝叶斯框架和方法，用于异构数据集的系统分析；(2)定义新的基于客观的不确定性量化方法，以评估模型不确定性和数据的重要性，从而使累积分析能够提高系统理解并优化未来的实验设计；(3)针对不同的操作目标，导出基于不确定性量化的最优贝叶斯实验设计，最大限度地利用现有数据，实现有效的未来实验设计和系统干预；(4)应用已开发的方法来了解和治疗特定疾病，例如癌症和1型糖尿病；与生命和材料科学的合作者合作，以有效的方式设计新材料发现的实验，将知识转化为实际应用。该项目将为将现有数据转化为对生命、疾病和人造系统的系统理解奠定基础，以获得更深入的见解，并指导它们实现有利于人类社会的理想系统行为。

The advancement of high-throughput high-content data acquisition techniques has pushed modern scientific research from traditional reductionism to constructionism for studying complex systems with a strong data-driven focus. However, there are still significant issues in big-data analytics, especially, regarding the reproducibility of data-driven research findings. To enable analytic methods from traditional reductionist scientific research to constructionist research with the help of rich data, an integrative Bayesian framework is proposed for systems prediction and intervention in high-dimensional network-based systems, which will provide ways to translate the unprecedented amount of heterogeneous data into reproducible scientific knowledge in a cumulative manner with novel concepts of objective-based uncertainty quantification and optimal experiment design based on that. The proposed knowledge-driven analytics has strong potential of transforming available diverse large-scale data for reproducible knowledge to drive life and materials science research. If successful, it can eventually lead to computational tools for more efficient experiment design to maximize the use of existing big data and speed up the process for effective disease therapeutics and new materials discovery. The interdisciplinary nature of this proposal promises to foster cross-fertilization of ideas between engineering, life science, and materials science through research and education. The broader impact of this proposal involves the integration of the proposed research with an educational plan: (1) to strengthen interactions with the collaborators in life and materials sciences. In addition to making all the tools and research outcomes from this project publicly available, the developed algorithms and tools, including necessary technical help, will be distributed to the collaborators for more effective collaboration; (2) to develop new courses interfacing engineering, mathematics, life and materials sciences and incorporate them into the engineering curriculum for education and research training of students at all levels, which will help the new generation of researchers to establish a broad and solid foundation for interdisciplinary research and prepare them with required skills to address real-world challenges. The courses will be available across campus to attract female and minority students who are interested in research in science and engineering; (3) to involve both undergraduate and graduate students in the research in this interdisciplinary field with the efforts to increasing the participation of underrepresented groups in science and engineering through the collaborations with the REU programs and other scholarship programs developed to increase diversity at Texas A&M University (TAMU). The scientific focus of this proposal is solving mathematical and computational problems that exist in high-dimensional network-based systems prediction and intervention with uncertain models. The following open problems will be addressed: (1) to develop a network-based Bayesian framework and methods for systematic analysis of heterogeneous data sets; (2) to define novel objective-based uncertainty quantification for assessing model uncertainty and data significance to enable cumulative analytics to improve systems understanding and optimize future experiment design; (3) to derive optimal Bayesian experiment design based on uncertainty quantification for different operational objectives, which can lead to the maximal use of existing data and effective future experiment design and systems intervention; and (4) to apply the developed methodologies for understanding and treating specific diseases, for example, cancer and type 1 diabetes; as well as designing experiments for new materials discovery in an efficient way, in collaboration with the collaborators in life and materials sciences, which will translate the knowledge to practical applications. This project will lay out the foundation for translating existing data into systems understanding of life, disease, and man-made systems to gain deeper insights and direct them to desirable systems behavior to benefit human society.