TY - JOUR
T1 - Deregulation upon DNA damage revealed by joint analysis of context-specific perturbation data
AU - Szczurek, Ewa
AU - Markowetz, Florian
AU - Gat-Viks, Irit
AU - Biecek, Przemysław
AU - Tiuryn, Jerzy
AU - Vingron, Martin
N1 - Funding Information:
The authors are grateful to Szymon Kielbasa for help in using TransFind for TF prediction. This work is supported in part by the SFB 618 grant of the Deutsche Forschungsgesellschaft (DFG), the Polish Ministry of Science and Higher Education grant no. N N 301 065236, Cancer Research UK, and Human Frontier Science Program Organization.
PY - 2011/6/21
Y1 - 2011/6/21
N2 - Background: Deregulation between two different cell populations manifests itself in changing gene expression patterns and changing regulatory interactions. Accumulating knowledge about biological networks creates an opportunity to study these changes in their cellular context.Results: We analyze re-wiring of regulatory networks based on cell population-specific perturbation data and knowledge about signaling pathways and their target genes. We quantify deregulation by merging regulatory signal from the two cell populations into one score. This joint approach, called JODA, proves advantageous over separate analysis of the cell populations and analysis without incorporation of knowledge. JODA is implemented and freely available in a Bioconductor package 'joda'.Conclusions: Using JODA, we show wide-spread re-wiring of gene regulatory networks upon neocarzinostatin-induced DNA damage in Human cells. We recover 645 deregulated genes in thirteen functional clusters performing the rich program of response to damage. We find that the clusters contain many previously characterized neocarzinostatin target genes. We investigate connectivity between those genes, explaining their cooperation in performing the common functions. We review genes with the most extreme deregulation scores, reporting their involvement in response to DNA damage. Finally, we investigate the indirect impact of the ATM pathway on the deregulated genes, and build a hypothetical hierarchy of direct regulation. These results prove that JODA is a step forward to a systems level, mechanistic understanding of changes in gene regulation between different cell populations.
AB - Background: Deregulation between two different cell populations manifests itself in changing gene expression patterns and changing regulatory interactions. Accumulating knowledge about biological networks creates an opportunity to study these changes in their cellular context.Results: We analyze re-wiring of regulatory networks based on cell population-specific perturbation data and knowledge about signaling pathways and their target genes. We quantify deregulation by merging regulatory signal from the two cell populations into one score. This joint approach, called JODA, proves advantageous over separate analysis of the cell populations and analysis without incorporation of knowledge. JODA is implemented and freely available in a Bioconductor package 'joda'.Conclusions: Using JODA, we show wide-spread re-wiring of gene regulatory networks upon neocarzinostatin-induced DNA damage in Human cells. We recover 645 deregulated genes in thirteen functional clusters performing the rich program of response to damage. We find that the clusters contain many previously characterized neocarzinostatin target genes. We investigate connectivity between those genes, explaining their cooperation in performing the common functions. We review genes with the most extreme deregulation scores, reporting their involvement in response to DNA damage. Finally, we investigate the indirect impact of the ATM pathway on the deregulated genes, and build a hypothetical hierarchy of direct regulation. These results prove that JODA is a step forward to a systems level, mechanistic understanding of changes in gene regulation between different cell populations.
UR - http://www.scopus.com/inward/record.url?scp=79959266404&partnerID=8YFLogxK
U2 - 10.1186/1471-2105-12-249
DO - 10.1186/1471-2105-12-249
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
AN - SCOPUS:79959266404
SN - 1471-2105
VL - 12
JO - BMC Bioinformatics
JF - BMC Bioinformatics
M1 - 249
ER -