PubMed · 1994 · 5.1K citations · 9 references
Life SciencesBioinformaticsComputational BiologyMachine LearningSequence AnalysisMotif DiscoveryPattern RecognitionProtein MotifsProtein Sequence AnalysisSequence MiningSequence Pattern RecognitionExpectation-maximizationExpectation-maximization AlgorithmFinite Mixture ModelsMixture ModelMotif DetectionMotif Occurrence ModelingProbabilistic Motif ModelsSequence Motif Discovery
The study presents an algorithm that uses expectation maximization to fit a two‑component finite mixture model for discovering motifs in unaligned DNA or protein sequences. The method iteratively fits a mixture model, probabilistically masks found motifs, and repeats until multiple motifs are identified, requiring only unaligned sequences and a motif width, and outputs motif models, thresholds for Bayes‑optimal classification, and alignments of motif occurrences. The algorithm successfully identifies several distinct motifs with varying occurrence counts within a single dataset.
The algorithm described in this paper discovers one or more motifs in a collection of DNA or protein sequences by using the technique of expectation maximization to fit a two-component finite mixture model to the set of sequences. Multiple motifs are found by fitting a mixture model to the data, probabilistically erasing the occurrences of the motif thus found, and repeating the process to find successive motifs. The algorithm requires only a set of unaligned sequences and a number specifying the width of the motifs as input. It returns a model of each motif and a threshold which together can be used as a Bayes-optimal classifier for searching for occurrences of the motif in other databases. The algorithm estimates how many times each motif occurs in each sequence in the dataset and outputs an alignment of the occurrences of the motif. The algorithm is capable of discovering several different motifs with differing numbers of occurrences in a single dataset.
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Michael Gribskov, Roland Lothy, David Eisenberg · Methods in enzymology on CD-ROM/Methods in enzymology · 1990 · 479 citations