  We consider the problem of estimating a sparse multi-response regression
function, with an application to expression quantitative trait locus (eQTL)
mapping, where the goal is to discover genetic variations that influence
gene-expression levels. In particular, we investigate a shrinkage technique
capable of capturing a given hierarchical structure over the responses, such as
a hierarchical clustering tree with leaf nodes for responses and internal nodes
for clusters of related responses at multiple granularity, and we seek to
leverage this structure to recover covariates relevant to each
hierarchically-defined cluster of responses. We propose a tree-guided group
lasso, or tree lasso, for estimating such structured sparsity under
multi-response regression by employing a novel penalty function constructed
from the tree. We describe a systematic weighting scheme for the overlapping
groups in the tree-penalty such that each regression coefficient is penalized
in a balanced manner despite the inhomogeneous multiplicity of group
memberships of the regression coefficients due to overlaps among groups. For
efficient optimization, we employ a smoothing proximal gradient method that was
originally developed for a general class of structured-sparsity-inducing
penalties. Using simulated and yeast data sets, we demonstrate that our method
shows a superior performance in terms of both prediction errors and recovery of
true sparsity patterns, compared to other methods for learning a
multivariate-response regression.
