Discovering multi-level structures in bio-molecular data through the Bernstein inequality

BMC Bioinformatics. 2008 Mar 26;9 Suppl 2(Suppl 2):S4. doi: 10.1186/1471-2105-9-S2-S4.

Abstract

Background: The unsupervised discovery of structures (i.e. clusterings) underlying data is a central issue in several branches of bioinformatics. Methods based on the concept of stability have been recently proposed to assess the reliability of a clustering procedure and to estimate the "optimal" number of clusters in bio-molecular data. A major problem with stability-based methods is the detection of multi-level structures (e.g. hierarchical functional classes of genes), and the assessment of their statistical significance. In this context, a chi-square based statistical test of hypothesis has been proposed; however, to assure the correctness of this technique some assumptions about the distribution of the data are needed.

Results: To assess the statistical significance and to discover multi-level structures in bio-molecular data, a new method based on Bernstein's inequality is proposed. This approach makes no assumptions about the distribution of the data, thus assuring a reliable application to a large range of bioinformatics problems. Results with synthetic and DNA microarray data show the effectiveness of the proposed method.

Conclusions: The Bernstein test, due to its loose assumptions, is more sensitive than the chi-square test to the detection of multiple structures simultaneously present in the data. Nevertheless it is less selective, that is subject to more false positives, but adding independence assumptions, a more selective variant of the Bernstein inequality-based test is also presented. The proposed methods can be applied to discover multiple structures and to assess their significance in different types of bio-molecular data.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms*
  • Computer Simulation
  • Databases, Factual
  • Gene Expression Profiling / methods*
  • Information Storage and Retrieval / methods
  • Models, Biological*
  • Oligonucleotide Array Sequence Analysis / methods*
  • Proteome / metabolism*
  • Signal Transduction / physiology*

Substances

  • Proteome