  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.
