Alignment-free clustering of transcription factor binding motifs using a genetic-k-medoids approach

Pilib Broin, Terry J. Smith, Aaron A J Golden

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background: Familial binding profiles (FBPs) represent the average binding specificity for a group of structurally related DNA-binding proteins. The construction of such profiles allows the classification of novel motifs based on similarity to known families, can help to reduce redundancy in motif databases and de novo prediction algorithms, and can provide valuable insights into the evolution of binding sites. Many current approaches to automated motif clustering rely on progressive tree-based techniques, and can suffer from so-called frozen sub-alignments, where motifs which are clustered early on in the process remain 'locked' in place despite the potential for better placement at a later stage. In order to avoid this scenario, we have developed a genetic-k-medoids approach which allows motifs to move freely between clusters at any point in the clustering process. Results: We demonstrate the performance of our algorithm, GMACS, on multiple benchmark motif datasets, comparing results obtained with current leading approaches. The first dataset includes 355 position weight matrices from the TRANSFAC database and indicates that the k-mer frequency vector approach used in GMACS outperforms other motif comparison techniques. We then cluster a set of 79 motifs from the JASPAR database previously used in several motif clustering studies and demonstrate that GMACS can produce a higher number of structurally homogeneous clusters than other methods without the need for a large number of singletons. Finally, we show the robustness of our algorithm to noise on multiple synthetic datasets consisting of known motifs convolved with varying degrees of noise. Conclusions: Our proposed algorithm is generally applicable to any DNA or protein motifs, can produce highly stable and biologically meaningful clusters, and, by avoiding the problem of frozen sub-alignments, can provide improved results when compared with existing techniques on benchmark datasets.

Original languageEnglish (US)
Article number22
JournalBMC Bioinformatics
Volume16
Issue number1
DOIs
StatePublished - Jan 28 2015

Fingerprint

Transcription factors
Transcription Factor
Cluster Analysis
Alignment
Transcription Factors
Clustering
Benchmarking
Databases
Noise
DNA
Position-Specific Scoring Matrices
Benchmark
DNA-binding Protein
Amino Acid Motifs
Nucleotide Motifs
DNA-Binding Proteins
Binding sites
Demonstrate
Placement
Specificity

Keywords

  • Clustering
  • Genetic algorithm
  • Motif
  • Transcription factor

ASJC Scopus subject areas

  • Applied Mathematics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Computer Science Applications

Cite this

Alignment-free clustering of transcription factor binding motifs using a genetic-k-medoids approach. / Broin, Pilib; Smith, Terry J.; Golden, Aaron A J.

In: BMC Bioinformatics, Vol. 16, No. 1, 22, 28.01.2015.

Research output: Contribution to journalArticle

Broin, Pilib ; Smith, Terry J. ; Golden, Aaron A J. / Alignment-free clustering of transcription factor binding motifs using a genetic-k-medoids approach. In: BMC Bioinformatics. 2015 ; Vol. 16, No. 1.
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