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In sequence-based predictions, conventionally an input sequence is represented by a multiple sequence alignment (MSA) or a representation derived from MSA, such as a position-specific scoring matrix. Recently, inspired by the development in…

Quantitative Methods · Quantitative Biology 2021-10-18 Nabil Ibtehaz , Daisuke Kihara

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

Potts statistical models have become a popular and promising way to analyze mutational covariation in protein Multiple Sequence Alignments (MSAs) in order to understand protein structure, function and fitness. But the statistical…

Quantitative Methods · Quantitative Biology 2019-03-13 Allan Haldane , Ronald M. Levy

Multiple sequence alignment (MSA) is a fundamental and ubiquitous technique in bioinformatics used to infer related residues among biological sequences. Thus alignment accuracy is crucial to a vast range of analyses, often in ways difficult…

Quantitative Methods · Quantitative Biology 2015-01-09 Stefano Iantorno , Kevin Gori , Nick Goldman , Manuel Gil , Christophe Dessimoz

We present the MSA-to-protein transformer, a generative model of protein sequences conditioned on protein families represented by multiple sequence alignments (MSAs). Unlike existing approaches to learning generative models of protein…

Biomolecules · Quantitative Biology 2022-04-05 Soumya Ram , Tristan Bepler

Multiple sequence alignment (MSA) has been one of the most important problems in bioinformatics for more decades and it is still heavily examined by many mathematicians and biologists. However, mostly because of the practical motivation of…

Quantitative Methods · Quantitative Biology 2015-11-17 Kristóf Takács

We give a short summary of the fixed-energy Multi-Scale Analysis (MSA) of the Anderson tight binding model in dimension $d\ge 1$ and show that this technique admits a straightforward extension to multi-particle systems. We hope that this…

Mathematical Physics · Physics 2020-04-25 Victor Chulaevsky

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

In the course of evolution, proteins show a remarkable conservation of their three-dimensional structure and their biological function, leading to strong evolutionary constraints on the sequence variability between homologous proteins. Our…

Quantitative Methods · Quantitative Biology 2014-04-07 Carlo Baldassi , Marco Zamparo , Christoph Feinauer , Andrea Procaccini , Riccardo Zecchina , Martin Weigt , Andrea Pagnani

Recent generative learning models applied to protein multiple sequence alignment (MSA) datasets include simple and interpretable physics-based Potts covariation models and other machine learning models such as MSA-Transformer (MSA-T). The…

Biological Physics · Physics 2025-10-28 Kisan Khatri , Ronald M. Levy , Allan Haldane

A grand canonical Monte Carlo (MC) algorithm is presented for studying the lattice gas model (LGM) of multiple protein sequence alignment, which coherently combines long-range interactions and variable-length insertions. MC simulations are…

Biomolecules · Quantitative Biology 2017-07-13 Akira R. Kinjo

Statistical coupling analysis (SCA) is a method for analyzing multiple sequence alignments that was used to identify groups of coevolving residues termed "sectors". The method applies spectral analysis to a matrix obtained by combining…

Biomolecules · Quantitative Biology 2015-06-19 Tiberiu Tesileanu , Lucy J. Colwell , Stanislas Leibler

Inverse statistical approaches to determine protein structure and function from Multiple Sequence Alignments (MSA) are emerging as powerful tools in computational biology. However the underlying assumptions of the relationship between the…

Biomolecules · Quantitative Biology 2016-11-17 Hugo Jacquin , Amy Gilson , Eugene Shakhnovich , Simona Cocco , Rémi Monasson

Several methods are available for the detection of covarying positions from a multiple sequence alignment (MSA). If the MSA contains a large number of sequences, information about the proximities between residues derived from covariation…

Quantitative Methods · Quantitative Biology 2014-04-29 Greg W. Clark , Sharon H. Ackerman , Elisabeth R. Tillier , Domenico L. Gatti

Analyzing the relation between a set of biological sequences can help to identify and understand the evolutionary history of these sequences and the functional relations among them. Multiple Sequence Alignment (MSA) is the main obstacle to…

Quantitative Methods · Quantitative Biology 2017-08-07 Sara Shehab , Sameh Shohdy , Arabi E. Keshk

Protein language models have excelled in a variety of tasks, ranging from structure prediction to protein engineering. However, proteins are highly diverse in functions and structures, and current state-of-the-art models including the…

Biomolecules · Quantitative Biology 2023-02-27 Chang Ma , Haiteng Zhao , Lin Zheng , Jiayi Xin , Qintong Li , Lijun Wu , Zhihong Deng , Yang Lu , Qi Liu , Lingpeng Kong

Protein structure prediction often hinges on multiple sequence alignments (MSAs), which underperform on low-homology and orphan proteins. We introduce PLAME, a lightweight MSA design framework that leverages evolutionary embeddings from…

Machine Learning · Computer Science 2025-09-29 Hanqun Cao , Xinyi Zhou , Zijun Gao , Chenyu Wang , Xin Gao , Zhi Zhang , Cesar de la Fuente-Nunez , Chunbin Gu , Ge Liu , Pheng-Ann Heng

Specific protein-protein interactions are crucial in the cell, both to ensure the formation and stability of multi-protein complexes, and to enable signal transduction in various pathways. Functional interactions between proteins result in…

Biological Physics · Physics 2016-11-21 Anne-Florence Bitbol , Robert S. Dwyer , Lucy J. Colwell , Ned S. Wingreen

Computational models starting from large ensembles of evolutionarily related protein sequences capture a representation of protein families and learn constraints associated to protein structure and function. They thus open the possibility…

Biomolecules · Quantitative Biology 2024-12-30 Damiano Sgarbossa , Umberto Lupo , Anne-Florence Bitbol

Amino acid sequence portrays most intrinsic form of a protein and expresses primary structure of protein. The order of amino acids in a sequence enables a protein to acquire a particular stable conformation that is responsible for the…

Machine Learning · Computer Science 2022-08-29 Ashish Ranjan , Md Shah Fahad , David Fernandez-Baca , Akshay Deepak , Sudhakar Tripathi
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