TY - GEN
T1 - A sparse regulatory network of copy-number driven expression reveals putative breast cancer oncogenes
AU - Yuan, Yinyin
AU - Curtis, Christina
AU - Caldas, Carlos
AU - Markowetz, Florian
PY - 2010
Y1 - 2010
N2 - The influence of DNA cis-regulatory elements on a gene's expression has been intensively studied. However, little is known about expressions driven by trans-acting DNA hotspots. DNA hotspots harboring copy number aberrations are recognized to be important in cancer as they influence multiple genes on a global scale. The challenge in detecting trans-effects is mainly due to the computational difficulty in detecting weak and sparse trans-acting signals amidst co-occuring passenger events. We propose an integrative approach to learn a sparse interaction network of DNA copy-number regions with their downstream targets in a breast cancer dataset. Information from this network helps distinguish copy-number driven from copy-number independent expression changes on a global scale. Our result further delineates cis- and trans-effects in a breast cancer dataset, for which important oncogenes such as ESR1 and ERBB2 appear to be highly copy-number dependent. Further, our model is shown to be efficient and in terms of goodness of fit no worse than other state-of the art predictors and network reconstruction models using both simulated and real data.
AB - The influence of DNA cis-regulatory elements on a gene's expression has been intensively studied. However, little is known about expressions driven by trans-acting DNA hotspots. DNA hotspots harboring copy number aberrations are recognized to be important in cancer as they influence multiple genes on a global scale. The challenge in detecting trans-effects is mainly due to the computational difficulty in detecting weak and sparse trans-acting signals amidst co-occuring passenger events. We propose an integrative approach to learn a sparse interaction network of DNA copy-number regions with their downstream targets in a breast cancer dataset. Information from this network helps distinguish copy-number driven from copy-number independent expression changes on a global scale. Our result further delineates cis- and trans-effects in a breast cancer dataset, for which important oncogenes such as ESR1 and ERBB2 appear to be highly copy-number dependent. Further, our model is shown to be efficient and in terms of goodness of fit no worse than other state-of the art predictors and network reconstruction models using both simulated and real data.
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U2 - 10.1109/BIBM.2010.5706612
DO - 10.1109/BIBM.2010.5706612
M3 - Conference contribution
AN - SCOPUS:79952420877
SN - 9781424483075
T3 - Proceedings - 2010 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2010
SP - 473
EP - 478
BT - Proceedings - 2010 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2010
T2 - 2010 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2010
Y2 - 18 December 2010 through 21 December 2010
ER -