Inferring causal models of cancer progression with a shrinkage estimator and probability raising

Olde Loohuis Loes, Caravagna Giulio, Graudenzi Alex, Ramazzotti Daniele, Mauri Giancarlo, Antoniotti Marco, Mishra Bud

(Submitted on 25 Nov 2013)

Existing techniques to reconstruct tree models of progression for accumulative processes such as cancer, seek to estimate causation by combining correlation and a frequentist notion of temporal priority. In this paper we define a novel theoretical framework to reconstruct such models based on the probabilistic notion of causation defined by Suppes, which differ fundamentally from that based on correlation. We consider a general reconstruction setting complicated by the presence of noise in the data, owing to the intrinsic variability of biological processes as well as experimental or measurement errors. To gain immunity to noise in the reconstruction performance we use a shrinkage estimator. On synthetic data, we show that our approach outperforms the state-of-the-art and, for some real cancer datasets, we highlight biologically significant differences revealed by the reconstructed progressions. Finally, we show that our method is efficient even with a relatively low number of samples and its performance quickly converges to its asymptote as the number of samples increases. Our analysis suggests the applicability of the method on small datasets of real patients.

http://arxiv.org/abs/1311.6293