Retrieval of Gene Expression Measurements with Probabilistic Models

Abstract

A crucial problem in current biological and medical research is how to utilize the diverse set of existing biological knowledge and heterogeneous measurement data in order to gain insights on new data. As datasets continue to be deposited in public repositories it is becoming important to develop search engines that can efficiently integrate existing data and search for relevant earlier studies given a new study. The search task is encountered in several biological applications including cancer genomics, pharmacokinetics, personalized medicine and meta-analysis of functional genomics.

Most existing search engines rely on classical keyword or annotation based retrieval which is limited to discovering known information and requires careful downstream annotation of the data. Data-driven model-based methods, that retrieve studies based on similarities in the actual measurement data, have a greater potential for uncovering novel biological insights. In particular, probabilistic modeling provides promising model-based tools due to its ability to encode prior knowledge, represent uncertainty in model parameters and handle noise associated to the data. By introducing latent variables it is further possible to capture relationships in data features in the form of meaningful biological components underlying the data.

This thesis adapts existing and develops new probabilistic models for retrieval of relevant measurement data in three different cases of background repositories. The first case is a background collection of data samples where each sample is represented by a single data type. The second case is a collection of multimodal data samples where each sample is represented by more than one data type. The third case is a background collection of datasets where each dataset, in turn, is a collection of multiple samples. In all three setups the proposed models are evaluated quantitatively and with case studies the models are demonstrated to facilitate interpretable retrieval of relevant data, rigorous integration of diverse information sources and learning of latent components from partly related dataset collections.