Suppr超能文献

对称性、规范自由度以及序列-功能关系的可解释性。

Symmetry, gauge freedoms, and the interpretability of sequence-function relationships.

作者信息

Posfai Anna, McCandlish David M, Kinney Justin B

机构信息

Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory.

出版信息

bioRxiv. 2025 Mar 17:2024.05.12.593774. doi: 10.1101/2024.05.12.593774.

Abstract

Quantitative models that describe how biological sequences encode functional activities are ubiquitous in modern biology. One important aspect of these models is that they commonly exhibit gauge freedoms, i.e., directions in parameter space that do not affect model predictions. In physics, gauge freedoms arise when physical theories are formulated in ways that respect fundamental symmetries. However, the connections that gauge freedoms in models of sequence-function relationships have to the symmetries of sequence space have yet to be systematically studied. In this work we study the gauge freedoms of models that respect a specific symmetry of sequence space: the group of position-specific character permutations. We find that gauge freedoms arise when model parameters transform under redundant irreducible matrix representations of this group. Based on this finding, we describe an "embedding distillation" procedure that enables both analytic calculation of the number of independent gauge freedoms and efficient computation of a sparse basis for the space of gauge freedoms. We also study how parameter transformation behavior affects parameter interpretability. We find that in many (and possibly all) nontrivial models, the ability to interpret individual model parameters as quantifying intrinsic allelic effects requires that gauge freedoms be present. This finding establishes an incompatibility between two distinct notions of parameter interpretability. Our work thus advances the understanding of symmetries, gauge freedoms, and parameter interpretability in models of sequence-function relationships.

摘要

描述生物序列如何编码功能活性的定量模型在现代生物学中无处不在。这些模型的一个重要方面是它们通常表现出规范自由度,即在参数空间中不影响模型预测的方向。在物理学中,当物理理论以尊重基本对称性的方式表述时,就会出现规范自由度。然而,序列 - 功能关系模型中的规范自由度与序列空间对称性之间的联系尚未得到系统研究。在这项工作中,我们研究了尊重序列空间特定对称性的模型的规范自由度:位置特异性字符置换群。我们发现,当模型参数在该群的冗余不可约矩阵表示下变换时,就会出现规范自由度。基于这一发现,我们描述了一种“嵌入蒸馏”程序,该程序既能对独立规范自由度的数量进行解析计算,又能高效计算规范自由度空间的稀疏基。我们还研究了参数变换行为如何影响参数的可解释性。我们发现,在许多(可能是所有)非平凡模型中,将单个模型参数解释为量化内在等位基因效应的能力要求存在规范自由度。这一发现确立了两种不同的参数可解释性概念之间的不相容性。因此,我们的工作推进了对序列 - 功能关系模型中的对称性、规范自由度和参数可解释性的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a84d/11956585/8770953c8332/nihpp-2024.05.12.593774v3-f0001.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验