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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…

Many non-coding RNAs are known to play a role in the cell directly linked to their structure. Structure prediction based on the sole sequence is however a challenging task. On the other hand, thanks to the low cost of sequencing…

Quantitative Methods · Quantitative Biology 2020-05-05 Francesca Cuturello , Guido Tiana , Giovanni Bussi

Statistical inference is central to many scientific endeavors, yet how it works remains unresolved. Answering this requires a quantitative understanding of the intrinsic interplay between statistical models, inference methods and data…

Determining which proteins interact together is crucial to a systems-level understanding of the cell. Recently, algorithms based on Direct Coupling Analysis (DCA) pairwise maximum-entropy models have allowed to identify interaction partners…

Biomolecules · Quantitative Biology 2020-03-25 Guillaume Marmier , Martin Weigt , Anne-Florence Bitbol

Direct-Coupling Analysis is a group of methods to harvest information about coevolving residues in a protein family by learning a generative model in an exponential family from data. In protein families of realistic size, this learning can…

Quantitative Methods · Quantitative Biology 2014-09-16 Magnus Ekeberg , Tuomo Hartonen , Erik Aurell

Global coevolutionary models of homologous protein families, as constructed by direct coupling analysis (DCA), have recently gained popularity in particular due to their capacity to accurately predict residue-residue contacts from sequence…

Quantitative Methods · Quantitative Biology 2019-09-23 Matteo Figliuzzi , Pierre Barrat-Charlaix , Martin Weigt

In high-throughput data, dynamic correlation between genes, i.e. changing correlation patterns under different biological conditions, can reveal important regulatory mechanisms. Given the complex nature of dynamic correlation, and the…

Applications · Statistics 2017-05-09 Tianwei Yu

In this methods article, we provide a flexible but easy-to-use implementation of Direct Coupling Analysis (DCA) based on Boltzmann machine learning, together with a tutorial on how to use it. The package \texttt{adabmDCA 2.0} is available…

Quantitative Methods · Quantitative Biology 2025-11-05 Lorenzo Rosset , Roberto Netti , Anna Paola Muntoni , Martin Weigt , Francesco Zamponi

Various approaches have explored the covariation of residues in multiple-sequence alignments of homologous proteins to extract functional and structural information. Among those are principal component analysis (PCA), which identifies the…

Biomolecules · Quantitative Biology 2013-08-28 Simona Cocco , Remi Monasson , Martin Weigt

Identifying protein-protein interactions is crucial for a systems-level understanding of the cell. Recently, algorithms based on inverse statistical physics, e.g. Direct Coupling Analysis (DCA), have allowed to use evolutionarily related…

Biomolecules · Quantitative Biology 2020-03-25 Carlos A. Gandarilla-Pérez , Pierre Mergny , Martin Weigt , Anne-Florence Bitbol

Proteins have evolved to perform diverse cellular functions, from serving as reaction catalysts to coordinating cellular propagation and development. Frequently, proteins do not exert their full potential as monomers but rather undergo…

Biomolecules · Quantitative Biology 2019-10-07 Guido Uguzzoni , Shalini John Lovis , Francesco Oteri , Alexander Schug , Hendrik Szurmant , Martin Weigt

In allosteric proteins, the binding of a ligand modifies function at a distant active site. Such allosteric pathways can be used as target for drug design, generating considerable interest in inferring them from sequence alignment data.…

Quantitative Methods · Quantitative Biology 2020-03-16 Barbara Bravi , Riccardo Ravasio , Carolina Brito , Matthieu Wyart

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

Canonical correlation analysis (CCA) is a widely used technique for estimating associations between two sets of multi-dimensional variables. Recent advancements in CCA methods have expanded their application to decipher the interactions of…

Machine Learning · Statistics 2025-02-05 Hongju Park , Shuyang Bai , Zhenyao Ye , Hwiyoung Lee , Tianzhou Ma , Shuo Chen

Longitudinal gene expression profiles of patients are collected in some clinical studies to monitor disease progression and understand disease etiology. The identification of gene sets that have coordinated changes with relevant clinical…

Methodology · Statistics 2016-09-27 Jiehuan Sun , Jose D. Herazo-Maya , Xiu Huang , Naftali Kaminski , Hongyu Zhao

To understand the biology of cancer, joint analysis of multiple data modalities, including imaging and genomics, is crucial. The involved nature of gene-microenvironment interactions necessitates the use of algorithms which treat both data…

Signal Processing · Electrical Eng. & Systems 2018-02-27 Vaishnavi Subramanian , Benjamin Chidester , Jian Ma , Minh N. Do

Principal component analysis (PCA) is often used for analyzing data in the most diverse areas. In this work, we report an integrated approach to several theoretical and practical aspects of PCA. We start by providing, in an intuitive and…

Computational Engineering, Finance, and Science · Computer Science 2021-06-09 Felipe L. Gewers , Gustavo R. Ferreira , Henrique F. de Arruda , Filipi N. Silva , Cesar H. Comin , Diego R. Amancio , Luciano da F. Costa

This paper presents Deep Dynamic Probabilistic Canonical Correlation Analysis (D2PCCA), a model that integrates deep learning with probabilistic modeling to analyze nonlinear dynamical systems. Building on the probabilistic extensions of…

Machine Learning · Computer Science 2025-02-10 Shiqin Tang , Shujian Yu , Yining Dong , S. Joe Qin

Generative probabilistic models emerge as a new paradigm in data-driven, evolution-informed design of biomolecular sequences. This paper introduces a novel approach, called Edge Activation Direct Coupling Analysis (eaDCA), tailored to the…

Biomolecules · Quantitative Biology 2024-04-29 Francesco Calvanese , Camille N. Lambert , Philippe Nghe , Francesco Zamponi , Martin Weigt

Canonical Correlation Analysis (CCA) is a classical tool for finding correlations among the components of two random vectors. In recent years, CCA has been widely applied to the analysis of genomic data, where it is common for researchers…

Machine Learning · Computer Science 2012-06-22 Sivaraman Balakrishnan , Kriti Puniyani , John Lafferty
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