Inferring differentiation pathways from gene expression.
BACKGROUND
The regulation of proliferation and differentiation of embryonic and adult stem cells into mature cells is central to developmental biology. Gene expression measured in distinguishable developmental stages helps to elucidate underlying molecular processes. In previous work we showed that functional gene modules, which act distinctly in the course of development, can be represented by a mixture of trees. In general, the similarities in the gene expression programs of cell populations reflect the similarities in the differentiation path.


RESULTS
We propose a novel model for gene expression profiles and an unsupervised learning method to estimate developmental similarity and infer differentiation pathways. We assess the performance of our model on simulated data and compare it with favorable results to related methods. We also infer differentiation pathways and predict functional modules in gene expression data of lymphoid development.


CONCLUSIONS
We demonstrate for the first time how, in principal, the incorporation of structural knowledge about the dependence structure helps to reveal differentiation pathways and potentially relevant functional gene modules from microarray datasets. Our method applies in any area of developmental biology where it is possible to obtain cells of distinguishable differentiation stages.


BACKGROUND
The implementation of our method (GPL license), data and additional results are available at http://algorithmics.molgen.mpg.de/Supplements/InfDif/.


BACKGROUND
Supplementary data is available at Bioinformatics online.
Costa
Ivan G
IG
Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany. filho@molgen.mpg.de
Roepcke
Stefan
S
Hafemeister
Christoph
C
Schliep
Alexander
A
D000465:Algorithms; D018797:Cell Cycle Proteins / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D003198:Computer Simulation; D020869:Gene Expression Profiling / Q000379:methods*; D008954:Models, Biological; D015398:Signal Transduction / Q000502:physiology*
D018797:Cell Cycle Proteins