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计算生物学的局限性。

Limits of computational biology.

作者信息

Bray Dennis

出版信息

In Silico Biol. 2015;12(1-2):1-7. doi: 10.3233/ISB-140461.

DOI:10.3233/ISB-140461
PMID:25318467
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4923711/
Abstract

Are we close to a complete inventory of living processes so that we might expect in the near future to reproduce every essential aspect necessary for life? Or are there mechanisms and processes in cells and organisms that are presently inaccessible to us? Here I argue that a close examination of a particularly well-understood system--that of Escherichia coli chemotaxis--shows we are still a long way from a complete description. There is a level of molecular uncertainty, particularly that responsible for fine-tuning and adaptation to myriad external conditions, which we presently cannot resolve or reproduce on a computer. Moreover, the same uncertainty exists for any process in any organism and is especially pronounced and important in higher animals such as humans. Embryonic development, tissue homeostasis, immune recognition, memory formation, and survival in the real world, all depend on vast numbers of subtle variations in cell chemistry most of which are presently unknown or only poorly characterized. Overcoming these limitations will require us to not only accumulate large quantities of highly detailed data but also develop new computational methods able to recapitulate the massively parallel processing of living cells.

摘要

我们是否已接近对生命过程的完整盘点,从而有望在不久的将来重现生命所需的每一个基本方面?或者细胞和生物体中是否存在目前我们无法触及的机制和过程?在此我认为,仔细研究一个特别容易理解的系统——大肠杆菌趋化性系统——表明我们距离完整描述仍有很长的路要走。存在一定程度的分子不确定性,尤其是负责微调以及适应无数外部条件的那部分,目前我们无法在计算机上解析或重现。此外,任何生物体中的任何过程都存在同样的不确定性,在诸如人类这样的高等动物中尤为显著且重要。胚胎发育、组织稳态、免疫识别、记忆形成以及在现实世界中的生存,所有这些都依赖于细胞化学中大量微妙的变化,其中大部分目前尚不清楚或仅得到粗略的描述。克服这些限制不仅需要我们积累大量高度详细的数据,还需要开发新的计算方法,以便能够重现活细胞的大规模并行处理。

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