Gillis, J., Pavlidis, P. (2009) A methodology for the analysis of differential coexpression across the human lifespan. BMC Bioinformatics, 10. p. 306. ISSN 14712105 (ISSN)
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Abstract
Background: Differential coexpression is a change in coexpression between genes that may reflect 'rewiring' of transcriptional networks. It has previously been hypothesized that such changes might be occurring over time in the lifespan of an organism. While both coexpression and differential expression of genes have been previously studied in life stage change or aging, differential coexpression has not. Generalizing differential coexpression analysis to many time points presents a methodological challenge. Here we introduce a method for analyzing changes in coexpression across multiple ordered groups (e.g., over time) and extensively test its validity and usefulness. Results: Our method is based on the use of the Haar basis set to efficiently represent changes in coexpression at multiple time scales, and thus represents a principled and generalizable extension of the idea of differential coexpression to life stage data. We used published microarray studies categorized by age to test the methodology. We validated the methodology by testing our ability to reconstruct Gene Ontology (GO) categories using our measure of differential coexpression and compared this result to using coexpression alone. Our method allows significant improvement in characterizing these groups of genes. Further, we examine the statistical properties of our measure of differential coexpression and establish that the results are significant both statistically and by an improvement in semantic similarity. In addition, we found that our method finds more significant changes in gene relationships compared to several other methods of expressing temporal relationships between genes, such as coexpression over time. Conclusion: Differential coexpression over age generates significant and biologically relevant information about the genes producing it. Our Haar basis methodology for determining age-related differential coexpression performs better than other tested methods. The Haar basis set also lends itself to ready interpretation in terms of both evolutionary and physiological mechanisms of aging and can be seen as a natural generalization of two-category differential coexpression. © 2009 Gillis and Pavlidis; licensee BioMed Central Ltd.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | adolescent adult aging article child DNA microarray gene expression gene function human infant lifespan methodology validation process Algorithms Computational Biology Databases, Genetic Gene Expression Profiling Genome, Human Humans Oligonucleotide Array Sequence Analysis |
| Subjects: | bioinformatics bioinformatics > genomics and proteomics > computers bioinformatics > genomics and proteomics Investigative techniques and equipment bioinformatics > genomics and proteomics > computers > computer software organism description > animal > mammal > primates > hominids > human |
| CSHL Authors: | |
| Depositing User: | Matt Covey |
| Date: | 2009 |
| Date Deposited: | 04 Apr 2013 13:51 |
| Last Modified: | 04 Apr 2013 13:51 |
| PMCID: | PMC2761903 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/28083 |
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