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Protein evolution involves mutations occurring across a wide range of time scales. In analogy with disordered systems in statistical physics, this dynamical heterogeneity suggests strong correlations between mutations happening at distinct…

Biomolecules · Quantitative Biology 2025-07-15 Saverio Rossi , Leonardo Di Bari , Martin Weigt , Francesco Zamponi

Signal transduction networks can form highly interconnected systems within cells due to network crosstalk, the sharing of input signals between multiple downstream responses. To better understand the evolutionary design principles…

Biological Physics · Physics 2018-02-14 Ammar Tareen , Ned S. Wingreen , Ranjan Mukhopadhyay

Viruses like influenza have long coevolved with host immune systems, gradually shaping the evolutionary trajectory of these pathogens. Host immune systems develop immunity against circulating strains, which in turn avoid extinction by…

Mechanisms of immunity, and of the host-pathogen interactions in general are among the most fundamental problems of medicine, ecology, and evolution studies. Here, we present a microscopic, protein-level, sequence-based model of immune…

Biomolecules · Quantitative Biology 2007-11-22 Muyoung Heo , Konstantin B. Zeldovich , Eugene I. Shakhnovich

The evolution of the full repertoire of proteins encoded in a given genome is mostly driven by gene duplications, deletions, and sequence modifications of existing proteins. Indirect information about relative rates and other intrinsic…

Genomics · Quantitative Biology 2008-03-25 Jacob Bock Axelsen , Koon-Kiu Yan , Sergei Maslov

BACKGROUND: Many of the mutations accumulated by naturally evolving proteins are neutral in the sense that they do not significantly alter a protein's ability to perform its primary biological function. However, new protein functions evolve…

Populations and Evolution · Quantitative Biology 2007-07-18 Jesse D Bloom , Philip A Romero , Zhongyi Lu , Frances H Arnold

We introduce a minimal model for the evolution of functional protein-interaction networks using a sequence-based mutational algorithm, and apply the model to study neutral drift in networks that yield oscillatory dynamics. Starting with a…

Molecular Networks · Quantitative Biology 2018-04-25 Md. Zulfikar Ali , Ned S. Wingreen , Ranjan Mukhopadhyay

Proteins are constructed from a limited alphabet of ~20 amino acids, yet the origins and selection of this specific alphabet are unresolved. One largely overlooked aspect is whether elemental composition constrains the range of viable…

Biomolecules · Quantitative Biology 2026-05-20 L. Felipe Benites , Louie Slocombe , Sara I. Walker

Multipartite viruses replicate through a puzzling evolutionary strategy. Their genome is segmented into two or more parts, and encapsidated in separate particles that appear to propagate independently. Completing the replication cycle,…

Physics and Society · Physics 2019-03-26 Eugenio Valdano , Susanna Manrubia , Sergio Gómez , Alex Arenas

The vertebrate adaptive immune system provides a flexible and diverse set of molecules to neutralize pathogens. Yet, viruses such as HIV can cause chronic infections by evolving as quickly as the adaptive immune system, forming an…

Populations and Evolution · Quantitative Biology 2016-06-22 Armita Nourmohammad , Jakub Otwinowski , Joshua B. Plotkin

With the exponential increase of the protein sequence databases over time, multiple-sequence alignment (MSA) methods, like PSI-BLAST, perform exhaustive and time-consuming database search to retrieve evolutionary information. The resulting…

Quantitative Methods · Quantitative Biology 2023-08-21 Issar Arab

Statistical analysis of alignments of large numbers of protein sequences has revealed "sectors" of collectively coevolving amino acids in several protein families. Here, we show that selection acting on any functional property of a protein,…

Biomolecules · Quantitative Biology 2019-04-26 Shou-Wen Wang , Anne-Florence Bitbol , Ned S. Wingreen

Survival analysis concerns the task of predicting the time until an event occurs. Often used in the medical field, survival analysis deals with incomplete (i.e., censored) data, for instance, from patients who did not experience the event…

Machine Learning · Computer Science 2026-05-29 Thalea Schlender , Peter A. N. Bosman , Tanja Alderliesten

Epistatic interactions between residues determine a protein's adaptability and shape its evolutionary trajectory. When a protein experiences a changed environment, it is under strong selection to find a peak in the new fitness landscape. It…

Populations and Evolution · Quantitative Biology 2016-04-01 Aditi Gupta , Christoph Adami

The structure of molecular networks derives from dynamical processes on evolutionary time scales. For protein interaction networks, global statistical features of their structure can now be inferred consistently from several…

Statistical Mechanics · Physics 2007-05-23 Johannes Berg , Michael Lässig , Andreas Wagner

Designing proteins de novo with tailored structural, physicochemical, and functional properties remains a grand challenge in biotechnology, medicine, and materials science, due to the vastness of sequence space and the complex coupling…

Artificial Intelligence · Computer Science 2025-12-01 Fiona Y. Wang , Di Sheng Lee , David L. Kaplan , Markus J. Buehler

Proteins, essential to biological systems, perform functions intricately linked to their three-dimensional structures. Understanding the relationship between protein structures and their amino acid sequences remains a core challenge in…

Quantitative Methods · Quantitative Biology 2024-11-04 Liang He , Peiran Jin , Yaosen Min , Shufang Xie , Lijun Wu , Tao Qin , Xiaozhuan Liang , Kaiyuan Gao , Yuliang Jiang , Tie-Yan Liu

The landscape of skeleton-based action representation learning has evolved from Contrastive Learning (CL) to Masked Auto-Encoder (MAE) architectures. However, each paradigm faces inherent limitations: CL often overlooks fine-grained local…

Computer Vision and Pattern Recognition · Computer Science 2026-03-13 Jeonghyeok Do , Yun Chen , Geunhyuk Youk , Munchurl Kim

The adaptive immune system engages in an arms race with evolving viruses, trying to generate new responses to viral strains that continually move away from the set of variants that have already elicited a functional immune response. In…

Populations and Evolution · Quantitative Biology 2024-06-04 David A. Kessler , Herbert Levine

Protein sequences are abundant in repeating segments, both as exact copies and as approximate segments with mutations. These repeats are important for protein structure and function, motivating decades of algorithmic work on repeat…

Machine Learning · Computer Science 2026-05-26 Gal Pomerants , Yaniv Nikankin , Anja Reusch , Tomer Tsaban , Ora Schueler-Furman , Yonatan Belinkov