Abstract

We explore the problem of variable selection in a case‐control setting with mass spectrometry proteomic data consisting of paired measurements. Each pair corresponds to a distinct isotope cluster and each component within pair represents a summary of isotopic expression based on either the intensity or the shape of the cluster. Our objective is to identify a collection of isotope clusters associated with the disease outcome and at the same time assess the predictive added‐value of shape beyond intensity while maintaining predictive performance. We propose a Bayesian model that exploits the paired structure of our data and utilizes prior information on the relative predictive power of each source by introducing multiple layers of selection. This allows us to make simultaneous inference on which are the most informative pairs and for which—and to what extent—shape has a complementary value in separating the two groups. We evaluate the Bayesian model on pancreatic cancer data. Results from the fitted model show that most predictive potential is achieved with a subset of just six (out of 1289) pairs while the contribution of the intensity components is much higher than the shape components. To demonstrate how the method behaves under a controlled setting we consider a simulation study. Results from this study indicate that the proposed approach can successfully select the truly predictive pairs and accurately estimate the effects of both components although, in some cases, the model tends to overestimate the inclusion probability of the second component.

Highlights

  • Proteomics is the large-scale study of proteins that aim to provide a better understanding of the function of cellular and disease processes at the protein level

  • We set the hyperparamaters of the Gamma distribution to α = β = 1 for the analysis presented in the paper, which results in a prior mean and variance of 1 for both sa and sb

  • We addressed the problem of isotope cluster selection through a Bayesian model formulation

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Summary

Introduction

Proteomics is the large-scale study of proteins that aim to provide a better understanding of the function of cellular and disease processes at the protein level. Ultrahigh-resolution mass spectrometers (MS) such as Fourier-transform MS have become the most powerful and efficient tools for the quantitative analysis of complex protein mixtures in biological systems. In ultrahigh-resolution mass spectrometry, each species (such as peptide) is detected and expressed as a “density” of isotope peaks (as shown in Figure 1B)—rather than a single peak—in the mass spectrum, resulting from the distribution of naturally occurring elements.

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