Latent variable based computational methods for applications in life sciences Analysis and integration of omics data sets
Sammanfattning: With the increasing availability of high-throughput systems for parallel monitoring of multiple variables, e.g. levels of large numbers of transcripts in functional genomics experiments, massive amounts of data are being collected even from single experiments. Extracting useful information from such systems is a non-trivial task that requires powerful computational methods to identify common trends and to help detect the underlying biological patterns. This thesis deals with the general computational problems of classifying and integrating high-dimensional empirical data using a latent variable based modeling approach. The underlying principle of this approach is that a complex system can be characterized by a few independent components that characterize the systematic properties of the system. Such a strategy is well suited for handling noisy, multivariate data sets with strong multicollinearity structures, such as those typically encountered in many biological and chemical applications.The main foci of the studies this thesis is based upon are applications and extensions of the orthogonal projections to latent structures (OPLS) method in life science contexts. OPLS is a latent variable based regression method that separately describes systematic sources of variation that are related and unrelated to the modeling aim (for instance, classifying two different categories of samples). This separation of sources of variation can be used to pre-process data, but also has distinct advantages for model interpretation, as exemplified throughout the work. For classification cases, a probabilistic framework for OPLS has been developed that allows the incorporation of both variance and covariance into classification decisions. This can be seen as a unification of two historical classification paradigms based on either variance or covariance. In addition, a non-linear reformulation of the OPLS algorithm is outlined, which is useful for particularly complex regression or classification tasks.The general trend in functional genomics studies in the post-genomics era is to perform increasingly comprehensive characterizations of organisms in order to study the associations between their molecular and cellular components in greater detail. Frequently, abundances of all transcripts, proteins and metabolites are measured simultaneously in an organism at a current state or over time. In this work, a generalization of OPLS is described for the analysis of multiple data sets. It is shown that this method can be used to integrate data in functional genomics experiments by separating the systematic variation that is common to all data sets considered from sources of variation that are specific to each data set.
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