Bayesian correlated clustering to integrate multiple datasets

Bioinformatics. 2012 Dec 15;28(24):3290-7. doi: 10.1093/bioinformatics/bts595. Epub 2012 Oct 9.

Abstract

Motivation: The integration of multiple datasets remains a key challenge in systems biology and genomic medicine. Modern high-throughput technologies generate a broad array of different data types, providing distinct-but often complementary-information. We present a Bayesian method for the unsupervised integrative modelling of multiple datasets, which we refer to as MDI (Multiple Dataset Integration). MDI can integrate information from a wide range of different datasets and data types simultaneously (including the ability to model time series data explicitly using Gaussian processes). Each dataset is modelled using a Dirichlet-multinomial allocation (DMA) mixture model, with dependencies between these models captured through parameters that describe the agreement among the datasets.

Results: Using a set of six artificially constructed time series datasets, we show that MDI is able to integrate a significant number of datasets simultaneously, and that it successfully captures the underlying structural similarity between the datasets. We also analyse a variety of real Saccharomyces cerevisiae datasets. In the two-dataset case, we show that MDI's performance is comparable with the present state-of-the-art. We then move beyond the capabilities of current approaches and integrate gene expression, chromatin immunoprecipitation-chip and protein-protein interaction data, to identify a set of protein complexes for which genes are co-regulated during the cell cycle. Comparisons to other unsupervised data integration techniques-as well as to non-integrative approaches-demonstrate that MDI is competitive, while also providing information that would be difficult or impossible to extract using other methods.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bayes Theorem
  • Chromatin Immunoprecipitation
  • Cluster Analysis
  • Gene Expression
  • Gene Expression Profiling / methods
  • Genomics / methods*
  • Models, Statistical*
  • Normal Distribution
  • Oligonucleotide Array Sequence Analysis
  • Protein Interaction Mapping
  • Saccharomyces cerevisiae / genetics
  • Systems Biology