Bioinformatics Knowledge Map for Analysis of Beta-Catenin Function in Cancer
| Author(s) | Çelen, İrem | |
| Author(s) | Ross, Karen E. | |
| Author(s) | Arighi, Cecilia N. | |
| Author(s) | Wu, Cathy H. | |
| Ordered Author | İrem Çelen, Karen E. Ross, Cecilia N. Arighi, Cathy H. Wu | |
| UD Author | Çelen, Irem | en_US |
| UD Author | Ross, Karen E. | en_US |
| UD Author | Arighi, Cecilia N. | en_US |
| UD Author | Wu, Cathy H. | en_US |
| Date Accessioned | 2015-12-15T16:30:08Z | |
| Date Available | 2015-12-15T16:30:08Z | |
| Copyright Date | Copyright ©2015 Çelen et al. | en_US |
| Publication Date | 2015-10-28 | |
| Description | Publisher's PDF. | en_US |
| Abstract | Given the wealth of bioinformatics resources and the growing complexity of biological information, it is valuable to integrate data from disparate sources to gain insight into the role of genes/proteins in health and disease. We have developed a bioinformatics framework that combines literature mining with information from biomedical ontologies and curated databases to create knowledge “maps” of genes/proteins of interest.We applied this approach to the study of beta-catenin, a cell adhesion molecule and transcriptional regulator implicated in cancer. The knowledge map includes post-translational modifications (PTMs), protein- protein interactions, disease-associated mutations, and transcription factors coactivated by beta-catenin and their targets and captures the major processes in which betacatenin is known to participate. Using the map, we generated testable hypotheses about beta-catenin biology in normal and cancer cells. By focusing on proteins participating in multiple relation types, we identified proteins that may participate in feedback loops regulating beta-catenin transcriptional activity. By combining multiple network relations with PTM proteoform- specific functional information, we proposed a mechanism to explain the observation that the cyclin dependent kinase CDK5 positively regulates beta-catenin co-activator activity. Finally, by overlaying cancer-associated mutation data with sequence features, we observed mutation patterns in several beta-catenin PTM sites and PTM enzyme binding sites that varied by tissue type, suggesting multiple mechanisms by which beta-catenin mutations can contribute to cancer. The approach described, which captures rich information for molecular species from genes and proteins to PTM proteoforms, is extensible to other proteins and their involvement in disease. | en_US |
| Department | University of Delaware. Center for Bioinformatics & Computational Biology. | en_US |
| Citation | Çelen İ, Ross KE, Arighi CN, Wu CH (2015) Bioinformatics Knowledge Map for Analysis of Beta- Catenin Function in Cancer. PLoS ONE 10(10): e0141773. doi:10.1371/journal.pone.0141773 | en_US |
| DOI | doi:10.1371/journal.pone.0141773 | en_US |
| ISSN | 1932-6203 | en_US |
| URL | http://udspace.udel.edu/handle/19716/17314 | |
| Language | en_US | en_US |
| Publisher | Public Library of Science | en_US |
| dc.rights | CC BY 4.0 (International) | en_US |
| dc.source | PLOS ONE | en_US |
| dc.source.uri | http://www.plosone.org/ | en_US |
| Title | Bioinformatics Knowledge Map for Analysis of Beta-Catenin Function in Cancer | en_US |
| Type | Article | en_US |
Files
Original bundle
1 - 1 of 1
Loading...
- Name:
- Bioinformatics Knowledge Map for Analysis of Beta-Catenin Function in Cancer_1447430317T7703.pdf
- Size:
- 5.6 MB
- Format:
- Adobe Portable Document Format
- Description:
License bundle
1 - 1 of 1
No Thumbnail Available
- Name:
- license.txt
- Size:
- 2.22 KB
- Format:
- Item-specific license agreed upon to submission
- Description: