Cited by 124Genomics and Phylogenetic StudiesProtein Structure and DynamicsRNA and protein synthesis mechanisms

Correlated mutations in models of protein sequences: phylogenetic and structural effects

Lapedes, Alan S., Giraud, Bertrand, Liu, LonChang, Stormo, Gary D.·1999·Institute of Mathematical Statistics Lecture Notes - Monograph Series

Abstract

Covariation analysis of sets of aligned sequences for RNA molecules is relatively successful in elucidating RNA secondary structure, as well as some aspects of tertiary structure [Gutell et al. (1992)].Covariation analysis of sets of aligned sequences for protein molecules is successful in certain instances in elucidating certain structural and functional links [Korber et al. (1993)], but in general, pairs of sites displaying highly covarying mutations in protein sequences do not necessarily correspond to sites that are spatially close in the protein structure [Gobel et al. (1994), Clarke (1995), Shindyalov et al. (1994), Thomas et al. (1996), Taylor &;Hatrick (1994), Neher (1994)].In this paper we identify two reasons why naive use of covariation analysis for protein sequences fails to reliably indicate sequence positions that are spatially proximate.The first reason involves the bias introduced in calculation of covariation measures due to the fact that biological sequences are generally related by a non-trivial phylogenetic tree.We present a null-model approach to solve this problem.The second reason involves linked chains of covariation which can result in pairs of sites displaying significant covariation even though they are not spatially proximate.We present a maximum entropy solution to this classic problem of "causation versus correlation".The methodologies are validated in simulation.

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Crossref · 10.1214/lnms/1215455556

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Authors
Lapedes, A. S., Giraud, B., Liu, L., & Stormo, G. D.
Affiliations
Santa Fe Institute (US)
Venue
Institute of Mathematical Statistics Lecture Notes - Monograph Series
Published
1999
Pages
236-256
ISSN
0749-2170 (ISSN-L)
OpenAlex
W1514077080
Cited by
124
References
30
Citations by year
2026: 1 · 2025: 6 · 2024: 6 · 2023: 7 · 2022: 4 · 2021: 13 · 2020: 9 · 2019: 16 · 2018: 9 · 2017: 8 · 2016: 9 · 2015: 7 · 2014: 14 · 2013: 7 · 2012: 3
FWCI
0.00
Type
book chapter
Language
en
Open access
closed
Locations
  • Lecture notes-monograph series (publishedVersion)
  • Project Euclid (Cornell University) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Keywords
correlated mutations, covariation analysis, protein sequences, phylogenetic bias, null models, correlation versus causation, maximum entropy, protein structure, protein tertiary structure

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