Prediction in a small-sized sample with a large number of covariates, the "small n, large p" problem, is challenging. This setting is encountered in multiple applications, such as in precision medicine, where obtaining additional data can be extremely costly or even impossible, and extensive research effort has recently been dedicated to finding principled solutions for accurate prediction. However, a valuable source of additional information, domain experts, has not yet been efficiently exploited. We formulate knowledge elicitation generally as a probabilistic inference process, where expert knowledge is sequentially queried to improve predictions. In the specific case of sparse linear regression, where we assume the expert has knowledge about the relevance of the covariates, or of values of the regression coefficients, we propose an algorithm and computational approximation for fast and efficient interaction, which sequentially identifies the most informative features on which to query expert knowledge. Evaluations of the proposed method in experiments with simulated and real users show improved prediction accuracy already with a small effort from the expert.

In a multisensory task, human adults integrate information from different sensory modalities -behaviorally in an optimal Bayesian fashion- while children mostly rely on a single sensor modality for decision making. The reason behind this change of behavior over age and the process behind learning the required statistics for optimal integration are still unclear and have not been justified by the conventional Bayesian modeling. We propose an interactive multisensory learning framework without making any prior assumptions about the sensory models. In this framework, learning in every modality and in their joint space is done in parallel using a single-step reinforcement learning method. A simple statistical test on confidence intervals on the mean of reward distributions is used to select the most informative source of information among the individual modalities and the joint space. Analyses of the method and the simulation results on a multimodal localization task show that the learning system autonomously starts with sensory selection and gradually switches to sensory integration. This is because, relying more on modalities -i.e. selection- at early learning steps (childhood) is more rewarding than favoring decisions learned in the joint space since, smaller state-space in modalities results in faster learning in every individual modality. In contrast, after gaining sufficient experiences (adulthood), the quality of learning in the joint space matures while learning in modalities suffers from insufficient accuracy due to perceptual aliasing. It results in tighter confidence interval for the joint space and consequently causes a smooth shift from selection to integration. It suggests that sensory selection and integration are emergent behavior and both are outputs of a single reward maximization process; i.e. the transition is not a preprogrammed phenomenon.

MotivationPrecision medicine requires the ability to predict the efficacies of different treatments for a given individual using high-dimensional genomic measurements. However, identifying predictive features remains a challenge when the sample size is small. Incorporating expert knowledge offers a promising approach to improve predictions, but collecting such knowledge is laborious if the number of candidate features is very large.ResultsWe introduce a probabilistic framework to incorporate expert feedback about the impact of genomic measurements on the outcome of interest and present a novel approach to collect the feedback efficiently, based on Bayesian experimental design. The new approach outperformed other recent alternatives in two medical applications: prediction of metabolic traits and prediction of sensitivity of cancer cells to different drugs, both using genomic features as predictors. Furthermore, the intelligent approach to collect feedback reduced the workload of the expert to approximately 11%, compared to a baseline approach.Availability and implementationSource code implementing the introduced computational methods is freely available at https://github.com/AaltoPML/knowledge-elicitation-for-precision-medicine.Supplementary information Supplementary data are available at Bioinformatics online.