Workshop on Multiscale Modeling and Analysis of Complex Data in Biomedical Sciences, RPI Campus, Troy, NY

1105405，国际生物学联合会将组织一个为期两天的研讨会，通过融合数学和生物科学，研究复杂系统生物学问题的建模、控制、计算、模拟、知识提取和可视化的多尺度方法。结构/功能关系范式是理解生物系统功能的核心。这个想法看起来很简单：了解生物系统的结构组织，从巨大的生态系统到单个蛋白质的形状，揭示了系统的功能。这个概念足够强大，激发了长达200年的努力，以更详细地描述我们生物宇宙的组成部分，从Linnean基于其结构相似性对生物进行分类的分类系统开始，最后是微尺度的描述，如包括人类在内的几种生物的完整基因组。因此，生物研究的简化论方法几代人以来一直占据主导地位，因此，我们现在了解了核苷酸的线性排列如何编码氨基酸的线性排列，蛋白质如何相互作用形成信号转导和代谢路径等功能基团。但在生物组织的每个层面上，我们都遇到了一堵墙--将复杂的生物宇宙缩减为无数微小的部分，我们遇到了新的复杂性形式：数据过载和“维度诅咒”。简单地说，我们已经拆开了我们的生物机器，但无法将它们重新组合在一起--我们积累简化论数据的能力已经超过了我们理解它的能力。因此，我们在结构/功能关系上遇到了一个缺口：在积累了大量关于生物结构的详细信息后，我们无法以一种解释这些结构执行相应复杂生物学功能的方式对其进行组装。这个缺口在组织层面上尤其明显，在组织层面上，大多数疾病和损伤都是显而易见的。心脏病和癌症仍然是美国的两大死因。这两种疾病的一个基本特征是组织衰竭：即受影响组织中细胞的结构组织和功能错误。同样，据估计，每年有六分之一的美国居民因受伤而需要接受治疗，但伤口愈合的过程如此复杂，以至于很难准确预测最严重的伤口将以多快的速度愈合。现有的伤口愈合模型依赖于临床上相关但有些肤浅的组织状态测量，如伤口面积减少、伤口边缘线性推进、疼痛和易用性。事实上，尽管有大量的基因筛查、生化分析和成像技术，但诊断和评估的“黄金标准”仍然是训练有素的病理学家的专家意见，他们扫描组织病理学切片中的组织样本。换句话说，人眼是目前我们可以用来识别疾病和受损组织结构和功能变化的最准确的工具。很明显，人类的判断并不是万无一失的：每年有数千种疾病被误诊，浪费或无效的医疗成本高达数亿美元。为了改进疾病和创伤的诊断和治疗，我们需要更好地了解大量的细胞和亚细胞部分是如何组织成功能组织的。实现这一点的一个策略是使用稳健的方法来描述复杂系统，这些方法适用于远远超出传统生物医学领域的数学和工程学科。从这个角度来看，组织的组织和功能可以被视为一个设计优化问题：例如，什么是细胞成分的最佳布置，才能实现最佳的组织性能？因此，拟议的研讨会的广泛影响是巨大的。

1105405, YenerThe PI will organize a two day workshop which will examine multiscale approaches to modeling, control, computation, simulation, knowledge extraction, and visualization of complex systems biology problems by merging mathematical and biological sciences.The structure/function relationship paradigm is central to understanding how biological systems function. The idea is deceptively simple: understanding the structural organization of biological systems, from massive ecological systems to the shape of a single protein, reveals the function of the system. The concept is powerful enough to have inspired a 200+ year-long effort to describe the components of our biological universe in ever finer detail, beginning with the Linnean taxonomic system of cataloging organisms based on their structural similarities, and culminating with microscale descriptions such as the complete genomes of several organisms, including humans. The reductionist approach to biological research has thus reigned supreme for generations, and as a result we now understand how the linear arrangement of nucleotides encodes the linear arrangement of amino acids, how proteins interact to form functional groups such as signal transduction and metabolic pathways, etc. But at each level of biological organization, we reach a wall- having reduced the complex biological universe to a myriad of minute parts, we encounter new forms of complexity: data overload and the "curse of dimensionality." Simply put, we've taken our biological machines apart but can?t put them back together again- our ability to accumulate reductionist data has outstripped our ability to understand it. Thus, we encounter a gap in the structure/function relationship: having accumulated an extraordinary amount of detailed information about biological structures, we can't assemble it in a way that explains the correspondingly complex biological functions these structures perform.This gap is especially evident at the level of tissues, where most diseases and injuries are manifest. Heart disease and cancer remain the top two causes of death in the United States. One fundamental characteristic of both diseases is tissue failure: namely, errors in the structural organization and function of cells in the affected tissues. Likewise, it is estimated that one in six US residents requires medical treatment for an injury each year, yet the process of wound healing is so complex it is difficult to accurately predict how quickly most serious wounds will heal. Existing models of wound healing rely on clinically relevant, but somewhat superficial, measures of tissue state such as reduction in wound area, linear advancement of wound edge, pain, and ease of use. In fact, despite a multitude of genetic screens, biochemical assays, and imaging techniques, the "gold standard" for diagnosis and evaluation remains the expert opinion of highly trained pathologists who scan samples of the tissues in histopathology slides. In other words, the human eye is currently the most accurate tool we have available for identifying telltale alterations in the structure and function of diseased and damaged tissues. And it is clear that human judgment is not fail-proof: thousands of diseases are misdiagnosed every year, costing hundreds of millions of dollars in wasted or ineffective medical treatment. To improve diagnosis and treatment of diseases and wounds, we need a better understanding of how the tremendous number of cellular and subcellular parts is organized into functional tissues. One strategy for achieving this is to employ robust methods for describing complex systems, adapted from math and engineering disciplines far outside traditional biomedical fields. Viewed from this perspective, tissue organization and function can be treated as a design optimization problem: e.g., what is the optimal arrangement of cellular constituents that achieves the best tissue performance? Thus the broader impacts of the proposed workshop is immense.