Global regulatory architecture of human, mouse and rat tissue transcriptomes
- Equal contributors
1 Department of Biology, ETH Zurich, 8092 Zurich, Switzerland
2 Nebion AG, Hohlstrasse 515, 8048 Zurich, Switzerland
3 Swiss Institute of Bioinformatics, Universitätstr. 6, 8092 Zurich, Switzerland
4 Department of Computer Science, ETH Zurich, 8092 Zurich, Switzerland
5 University College London, Gower Street, London, WC1E 6BT, UK
BMC Genomics 2013, 14:716 doi:10.1186/1471-2164-14-716Published: 20 October 2013
Predicting molecular responses in human by extrapolating results from model organisms requires a precise understanding of the architecture and regulation of biological mechanisms across species.
Here, we present a large-scale comparative analysis of organ and tissue transcriptomes involving the three mammalian species human, mouse and rat. To this end, we created a unique, highly standardized compendium of tissue expression. Representative tissue specific datasets were aggregated from more than 33,900 Affymetrix expression microarrays. For each organism, we created two expression datasets covering over 55 distinct tissue types with curated data from two independent microarray platforms. Principal component analysis (PCA) revealed that the tissue-specific architecture of transcriptomes is highly conserved between human, mouse and rat. Moreover, tissues with related biological function clustered tightly together, even if the underlying data originated from different labs and experimental settings. Overall, the expression variance caused by tissue type was approximately 10 times higher than the variance caused by perturbations or diseases, except for a subset of cancers and chemicals. Pairs of gene orthologs exhibited higher expression correlation between mouse and rat than with human. Finally, we show evidence that tissue expression profiles, if combined with sequence similarity, can improve the correct assignment of functionally related homologs across species.
The results demonstrate that tissue-specific regulation is the main determinant of transcriptome composition and is highly conserved across mammalian species.