突变的上下文依赖性：形式主义的链接
The context-dependence of mutations: a linkage of formalisms
摘要：
定义上位性的程度-突变效应的非独立性-对于理解生物系统中基因型、表型和适应性的关系至关重要。这些应用程序涵盖了生物研究的许多领域，包括生物化学，基因组学，蛋白质和系统工程，医学和进化生物学。然而，上位性的定量定义在不同的领域有所不同，它的分析超出了成对的影响仍然是模糊的。在这里，我们表明，不同的定义上位是一个单一的数学形式主义的版本-加权沃尔什-阿达玛变换。我们讨论的定义之一，背景平均上位性，是最翔实的目标是揭示一般上位性结构的生物系统，一个描述，可以是相当不同的本地上位性结构的特定模型系统。关键问题是选择有效的合奏平均和实际上对付巨大的组合复杂性的突变。在这方面，我们讨论了最佳学习生物系统上位结构的可能方法。
英文摘要：
Defining the extent of epistasis - the non-independence of the effects of mutations - is essential for understanding the relationship of genotype, phenotype, and fitness in biological systems. The applications cover many areas of biological research, including biochemistry, genomics, protein and systems engineering, medicine, and evolutionary biology. However, the quantitative definitions of epistasis vary among fields, and its analysis beyond just pairwise effects remains obscure in general. Here, we show that different definitions of epistasis are versions of a single mathematical formalism - the weighted Walsh-Hadamard transform. We discuss that one of the definitions, the backgound-averaged epistasis, is the most informative when the goal is to uncover the general epistatic structure of a biological system, a description that can be rather different from the local epistatic structure of specific model systems. Key issues are the choice of effective ensembles for averaging and to practically contend with the vast combinatorial complexity of mutations. In this regard, we discuss possible approaches for optimally learning the epistatic structure of biological systems.
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