Quantifying the relationship between co-expression, co-regulation and gene function.
BACKGROUND
It is thought that genes with similar patterns of mRNA expression and genes with similar functions are likely to be regulated via the same mechanisms. It has been difficult to quantitatively test these hypotheses on a large scale because there has been no general way of determining whether genes share a common regulatory mechanism. Here we use data from a recent genome wide binding analysis in combination with mRNA expression data and existing functional annotations to quantify the likelihood that genes with varying degrees of similarity in mRNA expression profile or function will be bound by a common transcription factor.


RESULTS
Genes with strongly correlated mRNA expression profiles are more likely to have their promoter regions bound by a common transcription factor. This effect is present only at relatively high levels of expression similarity. In order for two genes to have a greater than 50% chance of sharing a common transcription factor binder, the correlation between their expression profiles (across the 611 microarrays used in our study) must be greater than 0.84. Genes with similar functional annotations are also more likely to be bound by a common transcription factor. Combining mRNA expression data with functional annotation results in a better predictive model than using either data source alone.


CONCLUSIONS
We demonstrate how mRNA expression data and functional annotations can be used together to estimate the probability that genes share a common regulatory mechanism. Existing microarray data and known functional annotations are sufficient to identify only a relatively small percentage of co-regulated genes.
Allocco
Dominic J
DJ
Informatics Program, Children's Hospital, Boston, MA, USA. allocco@chip.org
Kohane
Isaac S
IS
Butte
Atul J
AJ
D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation / Q000235:genetics* / Q000502:physiology; D005796:Genes / Q000235:genetics / Q000502:physiology*; D005809:Genes, Regulator / Q000235:genetics / Q000502:physiology; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011237:Predictive Value of Tests; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D014157:Transcription Factors