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Protein contacts provide key information for the understanding of protein structure and function, and therefore contact prediction from sequences is an important problem. Recent research shows that some correctly predicted long-range…

Quantitative Methods · Quantitative Biology 2020-09-02 Siqi Sun

Self-supervised neural language models with attention have recently been applied to biological sequence data, advancing structure, function and mutational effect prediction. Some protein language models, including MSA Transformer and…

Biomolecules · Quantitative Biology 2022-10-25 Umberto Lupo , Damiano Sgarbossa , Anne-Florence Bitbol

Evolutionary dynamics are shaped by a variety of fundamental, generic drivers, including spatial structure, ecology, and selection pressure. These drivers impact the trajectory of evolution, and have been hypothesized to influence…

Populations and Evolution · Quantitative Biology 2025-06-04 Matthew Andres Moreno , Santiago Rodriguez-Papa , Emily Dolson

Learning Ising or Potts models from data has become an important topic in statistical physics and computational biology, with applications to predictions of structural contacts in proteins and other areas of biological data analysis. The…

Biological Physics · Physics 2018-09-19 Chen-Yi Gao , Hai-Jun Zhou , Erik Aurell

The sequence of amino acids in a protein is believed to determine its native state structure, which in turn is related to the functionality of the protein. In addition, information pertaining to evolutionary relationships is contained in…

Quantitative Methods · Quantitative Biology 2008-06-17 Kyung Dae Ko , Yoojin Hong , Gue Su Chang , Gaurav Bhardwaj , Damian B. van Rossum , Randen L. Patterson

As researchers collect increasingly large molecular data sets to reconstruct the Tree of Life, the heterogeneity of signals in the genomes of diverse organisms poses challenges for traditional phylogenetic analysis. A class of phylogenetic…

Populations and Evolution · Quantitative Biology 2015-09-11 Liang Liu , Zhenxiang Xi , Shaoyuan Wu , Charles Davis , Scott V. Edwards

The inability to resolve deep node relationships of highly divergent/rapidly evolving protein families is a major factor that stymies evolutionary studies. In this manuscript, we propose a Multiple Sequence Alignment (MSA) independent…

The analysis of correlations of amino acid occurrences in globular proteins has led to the development of statistical tools that can identify native contacts -- portions of the chains that come to close distance in folded structural…

Biomolecules · Quantitative Biology 2014-07-28 Rocío Espada , R. Gonzalo Parra , Thierry Mora , Aleksandra M. Walczak , Diego Ferreiro

Functional protein-protein interactions are crucial in most cellular processes. They enable multi-protein complexes to assemble and to remain stable, and they allow signal transduction in various pathways. Functional interactions between…

Biomolecules · Quantitative Biology 2018-11-14 Anne-Florence Bitbol

Phylogenetic networks extend phylogenetic trees to allow for modeling reticulate evolutionary processes such as hybridization. They take the shape of a rooted, directed, acyclic graph, and when parameterized with evolutionary parameters,…

Populations and Evolution · Quantitative Biology 2018-08-28 R. A. L. Elworth , H. A. Ogilvie , J. Zhu , L. Nakhleh

The similarity in the three-dimensional structures of homologous proteins imposes strong constraints on their sequence variability. It has long been suggested that the resulting correlations among amino acid compositions at different…

We present a sequence-based probabilistic formalism that directly addresses co-operative effects in networks of interacting positions in proteins, providing significantly improved contact prediction, as well as accurate quantitative…

Quantitative Methods · Quantitative Biology 2012-07-12 Alan Lapedes , Bertrand Giraud , Christopher Jarzynski

Phylogenetic mixtures model the inhomogeneous molecular evolution commonly observed in data. The performance of phylogenetic reconstruction methods where the underlying data is generated by a mixture model has stimulated considerable recent…

Populations and Evolution · Quantitative Biology 2007-06-30 Frederick A. Matsen , Mike Steel

Protein contacts contain important information for protein structure and functional study, but contact prediction from sequence remains very challenging. Both evolutionary coupling (EC) analysis and supervised machine learning methods are…

Quantitative Methods · Quantitative Biology 2015-04-09 Jianzhu Ma , Sheng Wang , Zhiyong Wang , Jinbo Xu

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

Identifying undocumented or potential future interactions among species is a challenge facing modern ecologists. Recent link prediction methods rely on trait data, however large species interaction databases are typically sparse and…

Applications · Statistics 2019-09-23 Mohamad Elmasri , Maxwell J. Farrell , T. Jonathan Davies , David A. Stephens

The time evolution of the formation probability of native bonds has been studied for designed sequences which fold fast into the native conformation. From this analysis a clear hierarchy of bonds emerge a) local, fast forming highly stable…

Condensed Matter · Physics 2009-10-31 G. Tiana , R. A. Broglia

Multiple sequence alignment (MSA) data play a crucial role in the study of protein mutations, with contact prediction being a notable application. Existing methods are often model-based or algorithmic and typically do not incorporate…

Methodology · Statistics 2026-01-23 Fan Yang , Zhao Ren , Wen Zhou , Kejue Jia , Robert Jernigan

Phylogenetic trees elucidate evolutionary relationships among species, but phylogenetic inference remains challenging due to the complexity of combining continuous (branch lengths) and discrete parameters (tree topology). Traditional Markov…

Populations and Evolution · Quantitative Biology 2024-12-30 ChenRui Duan , Zelin Zang , Siyuan Li , Yongjie Xu , Stan Z. Li

The algebraic properties of flattenings and subflattenings provide direct methods for identifying edges in the true phylogeny -- and by extension the complete tree -- using pattern counts from a sequence alignment. The relatively small…

Populations and Evolution · Quantitative Biology 2022-05-06 Joshua Stevenson , Barbara Holland , Michael Charleston , Jeremy Sumner