预测跨越人类蛋白质组的内在无序区域的分子语法，这一成果由圣路易斯的华盛顿大学Rohit V. Pappu团队经过不懈努力而取得。相关论文发表在2025年11月12日出版的《细胞》杂志上。

该团队引入了语法推断主题NARDINI+ (GIN)作为一种抵抗，它揭示了特定于IDR和跨越IDRome的语法。通过GIN激活分析，该课题组发现特定的IDR特征和GIN基因与不同的生物过程、细胞内定位偏好、专门的分子功能和功能化有关，这些都是通过细胞适应度相关性来评估的。具有特殊语法的IDR，被定义为具有高分非随机特征的序列，存在于蛋白质和复合体中，能够对核内的生化活动进行空间和时间排序。总体而言，GIN可以用于提取单个IDR或IDR基因组的序列-函数关系，重新设计现有IDR或重新设计IDR，通过分子语法和GIN基因组进行进化分析，以及理解IDR特异性疾病相关突变。

据了解，蛋白质的内在无序区（IDRs）是由分子语法定义的。这是指IDR特异性的非随机氨基酸组成和不同氨基酸类型对的非随机模式。

附：英文原文

Title: Molecular grammars of predicted intrinsically disordered regions that span the human proteome

Author: Kiersten M. Ruff, Matthew R. King, Alexander W. Ying, Vicky Liu, Avnika Pant, Whitney E. Lieberman, Min Kyung Shinn, Xiaolei Su, Cigall Kadoch, Rohit V. Pappu

Issue&Volume: 2025-11-12

Abstract: Intrinsically disordered regions (IDRs) of proteins are defined by molecular grammars. This refers to IDR-specific non-random amino acid compositions and non-random patterning of distinct pairs of amino acid types. Here, we introduce grammars inferred using NARDINI+ (GIN) as a resource that uncovers IDR-specific and IDRome-spanning grammars. Using GIN-enabled analyses, we find that specific IDR features and GIN clusters are associated with distinct biological processes, intra-cellular localization preferences, specialized molecular functions, and functionalization as assessed by cellular fitness correlations. IDRs with exceptional grammars, defined as sequences with high-scoring non-random features, are harbored in proteins and complexes that enable spatial and temporal sorting of biochemical activities within the nucleus. Overall, GIN can be used to extract sequence-function relationships of individual IDRs or clusters of IDRs, to redesign extant IDRs or design de novo IDRs, to perform evolutionary analyses through the lens of molecular grammars and GIN clusters, and to make sense of IDR-specific disease-associated mutations.

DOI: 10.1016/j.cell.2025.10.019

Source: https://www.cell.com/cell/abstract/S0092-8674(25)01191-2