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Statistical Methods for Identifying Conserved Residues in Multiple Sequence Alignment

  • Virpi Ahola , Tero Aittokallio , Esa Uusipaikka and Mauno Vihinen
Published/Copyright: October 30, 2004
Statistical Applications in Genetics and Molecular Biology
From the journal Statistical Applications in Genetics and Molecular Biology Volume 3 Issue 1

The assessment of residue conservation in a multiple sequence alignment is a central issue in bioinformatics. Conserved residues and regions are used to determine structural and functional motifs or evolutionary relationships between the sequences of a multiple sequence alignment. For this reason, residue conservation is a valuable measure for database and motif search or for estimating the quality of alignments. In this paper, we present statistical methods for identifying conserved residues in multiple sequence alignments. While most earlier studies examine the positional conservation of the alignment, we focus on the detection of individual conserved residues at a position. The major advantages of multiple comparison methods originate from their ability to select conserved residues simultaneously and to consider the variability of the residue estimates. Large-scale simulations were used for the comparative analysis of the methods. Practical performance was studied by comparing the structurally and functionally important residues of Src homology 2 (SH2) domains to the assignments of the conservation indices. The applicability of the indices was also compared in three additional protein families comprising different degrees of entropy and variability in alignment positions. The results indicate that statistical multiple comparison methods are sensitive and reliable in identifying conserved residues.

Keywords: Protein sequence analysis; residue conservation; conservation index; multiple comparison; SH2 domain
Published Online: 2004-10-30

©2011 Walter de Gruyter GmbH & Co. KG, Berlin/Boston

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https://doi.org/10.2202/1544-6115.1074
Keywords for this article
Protein sequence analysis; residue conservation; conservation index; multiple comparison; SH2 domain

Articles in the same Issue

  1. Article
  2. Using Alpha Wisely: Improving Power to Detect Multiple QTL
  3. Relating HIV-1 Sequence Variation to Replication Capacity via Trees and Forests
  4. Linear Models and Empirical Bayes Methods for Assessing Differential Expression in Microarray Experiments
  5. Asymptotic Optimality of Likelihood-Based Cross-Validation
  6. Using Importance Sampling to Improve Simulation in Linkage Analysis
  7. Model-Based Assignment and Inference of Protein Backbone Nuclear Magnetic Resonances
  8. Error-Rate and Decision-Theoretic Methods of Multiple Testing: Which Genes Have High Objective Probabilities of Differential Expression?
  9. Evaluation of Multiple Models to Distinguish Closely Related Forms of Disease Using DNA Microarray Data: an Application to Multiple Myeloma
  10. Saturation and Quantization Reduction in Microarray Experiments using Two Scans at Different Sensitivities
  11. Combining Nearest Neighbor Classifiers Versus Cross-Validation Selection
  12. Multiple Testing. Part I. Single-Step Procedures for Control of General Type I Error Rates
  13. Multiple Testing. Part II. Step-Down Procedures for Control of the Family-Wise Error Rate
  14. Augmentation Procedures for Control of the Generalized Family-Wise Error Rate and Tail Probabilities for the Proportion of False Positives
  15. Calculating the Statistical Significance of Changes in Pathway Activity From Gene Expression Data
  16. A Family-Based Association Test for Repeatedly Measured Quantitative Traits Adjusting for Unknown Environmental and/or Polygenic Effects
  17. Deletion/Substitution/Addition Algorithm in Learning with Applications in Genomics
  18. Classifying Gene Expression Profiles from Pairwise mRNA Comparisons
  19. Hierarchical Bayesian Neural Network for Gene Expression Temporal Patterns
  20. A Mixed Model Approach to Identify Yeast Transcriptional Regulatory Motifs via Microarray Experiments
  21. Mammalian Genomes Ease Location of Human DNA Functional Segments but Not Their Description
  22. On the Dependence Structure of Sequence Alignment Scores Calculated with Multiple Scoring Matrices
  23. Increasing Power for Tests of Genetic Association in the Presence of Phenotype and/or Genotype Error by Use of Double-Sampling
  24. A Method for Evaluating the Impact of Individual Haplotypes on Disease Incidence in Molecular Epidemiology Studies
  25. Statistical Methods for Identifying Conserved Residues in Multiple Sequence Alignment
  26. MergeMaid: R Tools for Merging and Cross-Study Validation of Gene Expression Data
  27. Sparse Inverse of Covariance Matrix of QTL Effects with Incomplete Marker Data
  28. Maximum Likelihood for Genome Phylogeny on Gene Content
  29. Confidence Levels for the Comparison of Microarray Experiments
  30. PLS Dimension Reduction for Classification with Microarray Data
  31. Statistical Analysis of Genomic Tag Data
  32. Statistical Analysis of Adsorption Models for Oligonucleotide Microarrays
  33. Statistical Significance Threshold Criteria For Analysis of Microarray Gene Expression Data
  34. A Compendium to Ensure Computational Reproducibility in High-Dimensional Classification Tasks
  35. Validation and Discovery in Markov Models of Genetics Data
  36. Making Sense of High-Throughput Protein-Protein Interaction Data
  37. Reader's Reaction
  38. Reader Reaction
  39. Response to Foulkes and De Gruttola
  40. Software Communication
  41. BayesMendel: an R Environment for Mendelian Risk Prediction
  42. Letter to the Editor
  43. Concerns About Unreliable Data from Spotted cDNA Microarrays Due to Cross-Hybridization and Sequence Errors
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