PSI-BLAST pseudocounts and the minimum description length principle

Position specific score matrices (PSSMs) are derived from multiple sequence alignments to aid in the recognition of distant protein sequence relationships. The PSI-BLAST protein database search program derives the column scores of its PSSMs with the aid of pseudocounts, added to the observed amino acid counts in a multiple alignment column. In the absence of theory, the number of pseudocounts used has been a completely empirical parameter. This article argues that the minimum description length principle can motivate the choice of this parameter. Specifically, for realistic alignments, the principle supports the practice of using a number of pseudocounts essentially independent of alignment size. However, it also implies that more highly conserved columns should use fewer pseudocounts, increasing the inter-column contrast of the implied PSSMs. A new method for calculating pseudocounts that significantly improves PSI-BLAST's; retrieval accuracy is now employed by default.

[1]  M. O. Dayhoff,et al.  Atlas of protein sequence and structure , 1965 .

[2]  C. Sander,et al.  Database of homology‐derived protein structures and the structural meaning of sequence alignment , 1991, Proteins.

[3]  S. Karlin,et al.  Methods for assessing the statistical significance of molecular sequence features by using general scoring schemes. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[4]  A G Murzin,et al.  SCOP: a structural classification of proteins database for the investigation of sequences and structures. , 1995, Journal of molecular biology.

[5]  Jun S. Liu,et al.  Detecting subtle sequence signals: a Gibbs sampling strategy for multiple alignment. , 1993, Science.

[6]  Michael Gribskov,et al.  Use of Receiver Operating Characteristic (ROC) Analysis to Evaluate Sequence Matching , 1996, Comput. Chem..

[7]  Jorma Rissanen,et al.  Minimum Description Length Principle , 2010, Encyclopedia of Machine Learning.

[8]  S. Altschul,et al.  Detection of conserved segments in proteins: iterative scanning of sequence databases with alignment blocks. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[9]  S. Henikoff,et al.  Position-based sequence weights. , 1994, Journal of molecular biology.

[10]  C. Chothia,et al.  Assessing sequence comparison methods with reliable structurally identified distant evolutionary relationships. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[11]  Anders Krogh,et al.  Maximum Entropy Weighting of Aligned Sequences of Proteins or DNA , 1995, ISMB.

[12]  Kenta Nakai,et al.  Pseudocounts for transcription factor binding sites , 2008, Nucleic acids research.

[13]  Gregory D. Schuler,et al.  Database resources of the National Center for Biotechnology Information , 2021, Nucleic Acids Res..

[14]  Rory A. Fisher,et al.  Theory of Statistical Estimation , 1925, Mathematical Proceedings of the Cambridge Philosophical Society.

[15]  S F Altschul,et al.  Weights for data related by a tree. , 1989, Journal of molecular biology.

[16]  S. Henikoff,et al.  Amino acid substitution matrices from protein blocks. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[17]  Gregory D. Schuler,et al.  Database resources of the National Center for Biotechnology Information: update , 2004, Nucleic acids research.

[18]  Thomas L. Madden,et al.  Improving the accuracy of PSI-BLAST protein database searches with composition-based statistics and other refinements. , 2001, Nucleic acids research.

[19]  Mark Gerstein,et al.  Changes in Protein Evolution Appendix : A method to weight protein sequences to correct for unequal representation , 1999 .

[20]  Thomas L. Madden,et al.  Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. , 1997, Nucleic acids research.

[21]  Patrice Koehl,et al.  The ASTRAL Compendium in 2004 , 2003, Nucleic Acids Res..

[22]  Sean R. Eddy,et al.  Maximum Discrimination Hidden Markov Models of Sequence Consensus , 1995, J. Comput. Biol..

[23]  Mark A. Pitt,et al.  Advances in Minimum Description Length: Theory and Applications , 2005 .

[24]  Alejandro A. Schäffer,et al.  IMPALA: matching a protein sequence against a collection of PSI-BLAST-constructed position-specific score matrices , 1999, Bioinform..

[25]  M. O. Dayhoff,et al.  22 A Model of Evolutionary Change in Proteins , 1978 .

[26]  P. Grünwald.  The Minimum Description Length Principle (Adaptive Computation and Machine Learning) , 2007 .

[27]  Maria Jesus Martin,et al.  The SWISS-PROT protein knowledgebase and its supplement TrEMBL in 2003 , 2003, Nucleic Acids Res..

[28]  David Haussler,et al.  Dirichlet mixtures: a method for improved detection of weak but significant protein sequence homology , 1996, Comput. Appl. Biosci..

[29]  Michael Gribskov,et al.  The Megaprior Heuristic for Discovering Protein Sequence Patterns , 1996, ISMB.

[30]  C. Chothia,et al.  Volume changes in protein evolution. , 1994, Journal of molecular biology.

[31]  P. Argos,et al.  Weighting aligned protein or nucleic acid sequences to correct for unequal representation. , 1990, Journal of molecular biology.

[32]  Julie Dawn Thompson,et al.  Improved sensitivity of profile searches through the use of sequence weights and gap excision , 1994, Comput. Appl. Biosci..

[33]  David Haussler,et al.  Using Dirichlet Mixture Priors to Derive Hidden Markov Models for Protein Families , 1993, ISMB.

[34]  M S Waterman,et al.  Identification of common molecular subsequences. , 1981, Journal of molecular biology.

[35]  Jorja G. Henikoff,et al.  Using substitution probabilities to improve position-specific scoring matrices , 1996, Comput. Appl. Biosci..

[36]  S. Henikoff,et al.  Amino acid substitution matrices. , 2000, Advances in protein chemistry.

[37]  S. Altschul.  Amino acid substitution matrices from an information theoretic perspective , 1991, Journal of Molecular Biology.

[38]  Osamu Gotoh,et al.  A weighting system and algorithm for aligning many phylogenetically related sequences , 1995, Comput. Appl. Biosci..

[39]  Thomas M. Cover,et al.  Elements of Information Theory , 2005 .