Tunable structure priors for Bayesian rule learning for knowledge integrated biomarker discovery

AIM To develop a framework to incorporate background domain knowledge into classification rule learning for knowledge discovery in biomedicine.METHODS Bayesian rule learning(BRL) is a rule-based classifier that uses a greedy best-first search over a space of Bayesian belief-networks(BN) to find the optimal BN to explain the input dataset, and then infers classification rules from this BN. BRL uses a Bayesian score to evaluate the quality of BNs. In this paper, we extended the Bayesian score to include informative structure priors, which encodes our prior domain knowledge about the dataset. We call this extension of BRL as BRL_p. The structure prior has a λ hyperparameter that allows the user to tune the degree of incorporation of the prior knowledge in the model learning process. We studied the effect of λ on model learning using a simulated dataset and a real-world lung cancer prognostic biomarker dataset, by measuring the degree of incorporation of our specified prior knowledge. We also monitored its effect on the model predictive performance. Finally, we compared BRL_p to other stateof-the-art classifiers commonly used in biomedicine.RESULTS We evaluated the degree of incorporation of prior knowledge into BRL_p, with simulated data by measuring the Graph Edit Distance between the true datagenerating model and the model learned by BRL_p. We specified the true model using informative structurepriors. We observed that by increasing the value of λ we were able to increase the influence of the specified structure priors on model learning. A large value of λ of BRL_p caused it to return the true model. This also led to a gain in predictive performance measured by area under the receiver operator characteristic curve(AUC). We then obtained a publicly available real-world lung cancer prognostic biomarker dataset and specified a known biomarker from literature [the epidermal growth factor receptor(EGFR) gene]. We again observed that larger values of λ led to an increased incorporation of EGFR into the final BRL_p model. This relevant background knowledge also led to a gain in AUC.CONCLUSION BRL_p enables tunable structure priors to be incorporated during Bayesian classification rule learning that integrates data and knowledge as demonstrated using lung cancer biomarker data.