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Related Experiment Videos

Scoring hidden Markov models

C Barrett1, R Hughey, K Karplus

  • 1Department of Computer Engineering, University of California, Santa Cruz 95064, USA.

Computer Applications in the Biosciences : CABIOS
|April 1, 1997
PubMed
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Choosing the right null model is crucial for accurate sequence comparison. A simple looping null model best identifies sequence matches using hidden Markov models (HMMs).

Area of Science:

  • Bioinformatics
  • Computational Biology
  • Statistical Modeling

Background:

  • Statistical sequence comparison methods like hidden Markov models (HMMs) and generalized profiles assess sequence probability against a model.
  • Log-odds scoring evaluates this probability by comparing it to a null hypothesis, a simpler model representing general sequences.
  • Key questions arise regarding the optimal null model and the appropriate log-odds score threshold for defining a match.

Purpose of the Study:

  • To experimentally analyze the selection of null models and score thresholds in statistical sequence comparison.
  • To compare the performance of different null models and scoring methods within the Sequence Alignment and Modeling (SAM) software suite.

Main Methods:

  • Experimental analysis of various null models and score thresholds within the Sequence Alignment and Modeling (SAM) software suite.

Related Experiment Videos

  • Comparison of HMMer's log-odds scoring and SAM's Z-scoring method.
  • Evaluation of a simple looping null model based on the geometric mean of column probabilities in HMMs.
  • Main Results:

    • A simple looping null model demonstrated strong or superior performance across four discrimination experiments.
    • The chosen null model effectively balances sequence probability against a general sequence universe.
    • Log-odds scoring effectiveness was analyzed in conjunction with different null models and thresholds.

    Conclusions:

    • The simple looping null model is a highly effective choice for statistical sequence comparison using HMMs.
    • This finding optimizes the process of identifying sequence matches and improves the accuracy of bioinformatics analyses.
    • The study provides practical insights for selecting null models and thresholds in sequence analysis tools.