Deregulation upon DNA damage revealed by joint analysis of context-specific perturbation data
<p>Abstract</p> <p>Background</p> <p>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 ch...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2011-06-01
|
| Series: | BMC Bioinformatics |
| Online Access: | http://www.biomedcentral.com/1471-2105/12/249 |
| _version_ | 1818496261328732160 |
|---|---|
| author | Biecek Przemysław Gat-Viks Irit Markowetz Florian Szczurek Ewa Tiuryn Jerzy Vingron Martin |
| author_facet | Biecek Przemysław Gat-Viks Irit Markowetz Florian Szczurek Ewa Tiuryn Jerzy Vingron Martin |
| author_sort | Biecek Przemysław |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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'.</p> <p>Conclusions</p> <p>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.</p> |
| first_indexed | 2024-12-10T18:31:08Z |
| format | Article |
| id | doaj.art-12e37ec639d04d1b9462d27dc0e531f3 |
| institution | Directory Open Access Journal |
| issn | 1471-2105 |
| language | English |
| last_indexed | 2024-12-10T18:31:08Z |
| publishDate | 2011-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Bioinformatics |
| spelling | doaj.art-12e37ec639d04d1b9462d27dc0e531f32022-12-22T01:37:56ZengBMCBMC Bioinformatics1471-21052011-06-0112124910.1186/1471-2105-12-249Deregulation upon DNA damage revealed by joint analysis of context-specific perturbation dataBiecek PrzemysławGat-Viks IritMarkowetz FlorianSzczurek EwaTiuryn JerzyVingron Martin<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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'.</p> <p>Conclusions</p> <p>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.</p>http://www.biomedcentral.com/1471-2105/12/249 |
| spellingShingle | Biecek Przemysław Gat-Viks Irit Markowetz Florian Szczurek Ewa Tiuryn Jerzy Vingron Martin Deregulation upon DNA damage revealed by joint analysis of context-specific perturbation data BMC Bioinformatics |
| title | Deregulation upon DNA damage revealed by joint analysis of context-specific perturbation data |
| title_full | Deregulation upon DNA damage revealed by joint analysis of context-specific perturbation data |
| title_fullStr | Deregulation upon DNA damage revealed by joint analysis of context-specific perturbation data |
| title_full_unstemmed | Deregulation upon DNA damage revealed by joint analysis of context-specific perturbation data |
| title_short | Deregulation upon DNA damage revealed by joint analysis of context-specific perturbation data |
| title_sort | deregulation upon dna damage revealed by joint analysis of context specific perturbation data |
| url | http://www.biomedcentral.com/1471-2105/12/249 |
| work_keys_str_mv | AT biecekprzemysław deregulationupondnadamagerevealedbyjointanalysisofcontextspecificperturbationdata AT gatviksirit deregulationupondnadamagerevealedbyjointanalysisofcontextspecificperturbationdata AT markowetzflorian deregulationupondnadamagerevealedbyjointanalysisofcontextspecificperturbationdata AT szczurekewa deregulationupondnadamagerevealedbyjointanalysisofcontextspecificperturbationdata AT tiurynjerzy deregulationupondnadamagerevealedbyjointanalysisofcontextspecificperturbationdata AT vingronmartin deregulationupondnadamagerevealedbyjointanalysisofcontextspecificperturbationdata |