Biomolecular Interaction Networks: Function and Disease

描述（由申请人提供）：本提案旨在请求对由安娜R. Panchenko，特雷莎Przytycka和安德烈Califano，这将是在魁北克，加拿大从2010年3月7日至12日举行。蛋白质、核酸和其他生物分子的功能只能通过它们在体内的相互作用来定义。这种生物化学相互作用--包括那些参与信号转导、转录和翻译调节以及大分子复合物组装的相互作用--在其规模和多样性方面令人惊讶。例如，已经表明大多数蛋白质与多个伙伴相互作用，形成复杂的相互作用网络。类似地，单个转录因子可以单独或以组合方式结合数万个基因组位点并调节数千个基因的表达。 调节相互作用在决定细胞分化、维持细胞和生物体内平衡以及触发导致人类疾病（包括癌症）的异常分化事件中起关键作用。毫不奇怪，即使是轻微的遗传和表观遗传干扰这些调控途径可以触发宏观变化，在正常细胞生理和导致疾病。由于大量的实验数据，研究人员开始揭示分子相互作用网络的一些一般规则和原则：它们的拓扑性质，它们的组成部分之间的关系，进化保守性和分歧，以及它们在维持特定细胞功能和过程中的作用。 尽管取得了重大进展，但是，关于许多蛋白质的不同功能作用的知识仍然是难以捉摸的。因此，相互作用网络已经成为非常有用的工具，在预测上下文特定的分子功能的基础上的上游调控，同源结合伙伴，和下游调控目标的知识。此外，分子相互作用网络开始提供一个独特的综合背景下，研究额外的疾病相关的遗传和表观遗传数据，包括单核苷酸突变和多态性，基因拷贝数改变和复杂的，多基因疾病。 公共卫生相关性：尽管基因组学和蛋白质组学领域取得了重大进展，但有关许多蛋白质和基因的独特功能作用的知识仍然难以捉摸。本次研讨会的目的是汇集来自计算和实验生物学，基因组学和蛋白质组学不同领域的研究人员，讨论使用生物分子相互作用网络来研究细胞功能和人类疾病。会议讨论的主题将为基因和蛋白质功能注释、基因调控和抗癌诊断和治疗提供新的方法。

DESCRIPTION (provided by applicant): This proposal is to request support for a Keystone Symposia meeting entitled Biomolecular Interaction Networks: Function and Disease, organized by Anna R. Panchenko, Teresa Przytycka and Andrea Califano, which will be held in Quibec, Canada from March 7 - 12, 2010. The function of proteins, nucleic acids, and other biomolecules can only be defined through their interactions in vivo. Such biochemical interactions - including those involved in signal transduction, transcriptional and translational regulation, as well as in the assembly of large molecular complexes - are astonishing in their magnitude and diversity. For instance, it has been shown that most proteins interact with multiple partners, forming intricate interaction networks. Similarly, an individual transcription factor can bind to tens of thousands of genomic sites and regulate the expression of thousands of genes, both in isolation and in combinatorial fashion. Regulatory interactions play a key role in determining cellular differentiation, in maintaining cellular and organism homeostasis, and in triggering abnormal differentiation events leading to human disease including cancer. Not surprisingly, even slight genetic and epigenetic perturbations of these regulatory pathways can trigger macroscopic changes in normal cell physiology and lead to disease. Due to the abundance of experimental data, researchers are starting to uncover some general rules and principles underlying molecular interaction networks: their topological properties, the relationships between their components, evolutionary conservation and divergence, and their role in maintaining specific cellular functions and processes. Despite significant advances, however, knowledge about the distinct functional roles of many proteins is still elusive. Thus, interaction networks have emerged as exceedingly useful tools in predicting context-specific molecular function based on knowledge of upstream regulators, cognate binding partners, and downstream regulated targets. Furthermore, molecular interaction networks are starting to provide a unique integrative context to study additional disease-related genetic and epigenetic data, including single nucleotide mutations and polymorphisms, gene copy number alterations and complex, polygenic diseases. PUBLIC HEALTH RELEVANCE: Despite significant advances in the fields of genomics and proteomics, knowledge about the distinct functional roles of many proteins and genes still remains elusive. The aim of this symposium is to bring together researchers from different fields of computational and experimental biology, genomics and proteomics, to discuss the use of biomolecular interaction networks to study cell function and human diseases. The topics discussed at the meeting will seed new approaches in gene and protein functional annotation, gene regulation and anti-cancer diagnostics and therapeutics.