Distributional Equivalence and Structure Learning for Bow-free Acyclic Path Diagrams

We consider the problem of structure learning for bow-free acyclic path diagrams (BAPs). BAPs can be viewed as a generalization of linear Gaussian DAG models that allow for certain hidden variables. We present a first method for this problem using a greedy score-based search algorithm. We also prove some necessary and some sufficient conditions for distributional equivalence of BAPs which are used in an algorithmic ap- proach to compute (nearly) equivalent model structures. This allows us to infer lower bounds of causal effects. We also present applications to real and simulated datasets using our publicly available R-package

Efficient network-guided multi-locus association mapping with graph cuts

As an increasing number of genome-wide association studies reveal the limitations of attempting to explain phenotypic heritability by single genetic loci, there is growing interest for associating complex phenotypes with sets of genetic loci. While several methods for multi-locus mapping have been proposed, it is often unclear how to relate the detected loci to the growing knowledge about gene pathways and networks. The few methods that take biological pathways or networks into account are either restricted to investigating a limited number of predetermined sets of loci, or do not scale to genome-wide settings. We present SConES, a new efficient method to discover sets of genetic loci that are maximally associated with a phenotype, while being connected in an underlying network. Our approach is based on a minimum cut reformulation of the problem of selecting features under sparsity and connectivity constraints that can be solved exactly and rapidly. SConES outperforms state-of-the-art competitors in terms of runtime, scales to hundreds of thousands of genetic loci, and exhibits higher power in detecting causal SNPs in simulation studies than existing methods. On flowering time phenotypes and genotypes from Arabidopsis thaliana, SConES detects loci that enable accurate phenotype prediction and that are supported by the literature. Matlab code for SConES is available at http://webdav.tuebingen.mpg.de/u/karsten/Forschung/scones/Comment: 20 pages, 6 figures, accepted at ISMB (International Conference on Intelligent Systems for Molecular Biology) 201