Temporal aggregation bias and inference of causal regulatory networks

J Comput Biol. 2004;11(5):971-85. doi: 10.1089/cmb.2004.11.971.


Time course experiments with microarrays have begun to provide a glimpse into the dynamic behavior of gene expression. In a typical experiment, scientists use microarrays to measure the abundance of mRNA at discrete time points after the onset of a stimulus. Recently, there has been much work on using these data to infer causal regulatory networks that model how genes influence each other. However, microarray studies typically have slow sampling rates that can lead to temporal aggregation of the signal. That is, each successive sampling point represents the sum of all signal changes since the previous sample. In this paper, we show that temporal aggregation can bias algorithms for causal inference and lead them to discover spurious relations that would not be found if the signal were sampled at a much faster rate. We discuss the implications of temporal aggregation on inference, the problems it creates, and potential directions for solutions.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Computational Biology*
  • Data Interpretation, Statistical*
  • Gene Expression Regulation
  • Oligonucleotide Array Sequence Analysis