Statistical mechanics of transcription-factor binding site discovery using hidden Markov models

DOI10.1007/S10955-010-0102-XMaRDI QIDQ540552zbMATH OpenOpenAlexWikidataFDO

Authors Pankaj Mehta, David Schwab, Anirvan Sengupta

Publication date 3 June 2011

Published in Journal of Statistical Physics (Search for Journal in Brave)

Full work available at URL https://arxiv.org/abs/1008.3151, http://europepmc.org/articles/pmc3407691

zbMATH Keywords

hidden Markov modelsbioinformaticsFisher informationmashine learningone-dimensional statistical mechanics

Mathematics Subject Classification ID

Applications of Markov chains and discrete-time Markov processes on general state spaces (social mobility, learning theory, industrial processes, etc.) (60J20) Protein sequences, DNA sequences (92D20) Memory and learning in psychology (91E40) Stochastic methods applied to problems in equilibrium statistical mechanics (82B31)

Abstract: Hidden Markov Models (HMMs) are a commonly used tool for inference of transcription factor (TF) binding sites from DNA sequence data. We exploit the mathematical equivalence between HMMs for TF binding and the "inverse" statistical mechanics of hard rods in a one-dimensional disordered potential to investigate learning in HMMs. We derive analytic expressions for the Fisher information, a commonly employed measure of confidence in learned parameters, in the biologically relevant limit where the density of binding sites is low. We then use techniques from statistical mechanics to derive a scaling principle relating the specificity (binding energy) of a TF to the minimum amount of training data necessary to learn it.

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Cites work

• A Maximization Technique Occurring in the Statistical Analysis of Probabilistic Functions of Markov Chains
• An invariant form for the prior probability in estimation problems
• Pattern recognition and machine learning.

Cited in

(4)

• Bioinformatic principles underlying the information content of transcription factor binding sites
• Bayesian Clustering of Transcription Factor Binding Motifs
• Learning quantitative sequence-function relationships from massively parallel experiments
• Coupling hidden Markov models for the discovery of Cis-regulatory modules in multiple species

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Uses Software

• PRMLT

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