Search for organising principles: understanding in systems biology
Search for organising principles: understanding in systems biology
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DOI：
10.1049/sb:20045010
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发表时间：
2004-06-01
期刊：
影响因子：
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通讯作者：
Keene, J. D.
中科院分区：
文献类型：
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作者：
Mesarovic, M. D.;Sreenath, S. N.;Keene, J. D.
在很大程度上由于分子生物学的爆炸性进展，生物学可以说已成为最令人兴奋的科学领域。 21世纪上半叶有时被称为“生物学时代”，类似于20世纪上半叶被认为是“物理学时代”。然而，生物学正面临一场危机——或者说这是一个机遇——让人想起双螺旋时代之前生物学的状态。系统生物学面临的主要挑战是复杂性。胡德表示，“系统生物学定义并分析一个功能系统中所有元素的相互关系，以了解该系统如何运作。”人类基因组中有 30000 多个基因，同时研究所有关系就成为一个极其复杂的问题。哈纳汉和温伯格提出了这样的问题：进步是否将包括“为已经复杂得几乎无法衡量的科学文献增加进一步的复杂性”，或者进步是否将导致“具有与化学或物理学相媲美的概念结构和逻辑连贯性的科学”。挑战的核心是需要一种新的方法，从还原论转向整体视角。然而，需要的不仅仅是宣布一种新方法。我们建议需要的是为系统生物学研究提供一个概念框架。我们提出复杂系统的概念，即数学一般系统理论（MGST）中定义的系统的系统，是提供这样一个框架的核心。我们进一步认为，为了更深入地理解系统生物学研究，应该超越建立数值数学或计算机模型——尽管它们很重要。生物现象无法像经典物理学那样以数值精度水平进行预测。关于系统类别如何组织以在不断变化的条件下发挥作用的解释更具启发性。非数字数学工具适合该任务。这种分类视角使我们提出，系统生物学的理解核心取决于对组织原则的探索，而不仅仅是构建准确概述系统在空间和时间上的演化的预测描述（即模型）。寻找组织原则需要识别/发现新概念和假设。本文概述了其中的一些，例如转录调控网络的协调基序和层次结构中 levccels 的有限自主性。概述了实验设计，以帮助验证相互作用平衡协调原理对转录和转录后网络的适用性。
Due in large measure to the explosive progress in molecular biology, biology has become arguably the most exciting scientific field. The first half of the 21st century is sometimes referred to as the 'era of biology', analogous to the first half of the 20th century, which was considered to be the 'era of physics'. Yet, biology is facing a crisis - or is it an opportunity - reminiscent of the state of biology in pre-double-helix time. The principal challenge facing systems biology is complexity. According to Hood, 'Systems biology defines and analyses the interrelationships of all of the elements in a functioning system in order to understand how the system works.' With 30000+ genes in the human genome the study of all relationships simultaneously becomes a formidably complex problem. Hanahan and Weinberg raised the question as to whether progress will consist of 'adding further layers of complexity to a scientific literature that is already complex almost beyond measure' or whether the progress will lead to a 'science with a conceptual structure and logical coherence that rivals that of chemistry or physics.' At the core of the challenge is the need for a new approach, a shift from reductionism to a holistic perspective. However, more than just a pronouncement of a new approach is needed. We suggest that what is needed is to provide a conceptual framework for systems biology research. We propose that the concept of a complex system, i.e. a system of systems as defined in mathematical general systems theory (MGST), is central to provide such a framework. We further argue that for a deeper understanding in systems biology investigations should go beyond building numerical mathematical or computer models - important as they are. Biological phenomena cannot be predicted with the level of numerical precision as in classical physics. Explanations in terms of how the categories of systems are organised to function in ever changing conditions are more revealing. Non-numerical mathematical tools are appropriate for the task. Such a categorical perspective led us to propose that the core of understanding in systems biology depends on the search for organising principles rather than solely on construction of predictive descriptions (i.e. models) that exactly outline the evolution of systems in space and time. The search for organising principles requires an identification/discovery of new concepts and hypotheses. Some of them, such as coordination motifs for transcriptional regulatory networks and bounded autonomy of levccels in a hierarchy, are outlined in this article. Experimental designs are outlined to help verify the applicability of the interaction balance principle of coordination to transcriptional and post-transcriptional networks.