Inferring differentiation pathways from gene expression

I.G. Costa, S. Roepcke, C. Hafemeister and A. Schliep

Bioinformatics 2008, 24:13, i156–164.

Motivation: 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. Availability: The implementation of our method (GPL license), data and additional results are available at Contact:, Supplementary information: Supplementary data is available at Bioinformatics online.

Supplementary information is available at A reprint is available as PDF.

Pubmed ID: 18586709.

The publication includes results from the following projects or software tools: PyMix, CellDiff.

The following presentation(s) are based on this publication: July 21, 2008 by Ivan Costa at International Conference of Intelligent Systems for Molecular Biology, Toronto, Canada (Contributed Talk).

Further publications by Alexander Schliep, Ivan G Costa, Christoph Hafemeister.