Motivation: Tandem mass spectrometry (MS/MS) offers fast and reliable characterization of complex protein mixtures, but suffers from low sensitivity in protein identification. In a typical shotgun proteomics experiment, it is assumed that all proteins are equally likely to be present. However, there is often other information available, e.g. the probability of a protein's presence is likely to correlate with its mRNA concentration.
Results: We develop a Bayesian score that estimates the posterior probability of a protein's presence in the sample given its identification in an MS/MS experiment and its mRNA concentration measured under similar experimental conditions. Our method, MSpresso, substantially increases the number of proteins identified in an MS/MS experiment at the same error rate, e.g. in yeast, MSpresso increases the number of proteins identified by approximately 40%. We apply MSpresso to data from different MS/MS instruments, experimental conditions and organisms (Escherichia coli, human), and predict 19-63% more proteins across the different datasets. MSpresso demonstrates that incorporating prior knowledge of protein presence into shotgun proteomics experiments can substantially improve protein identification scores.
Availability and implementation: Software is available upon request from the authors. Mass spectrometry datasets and supplementary information are available from (http://www.marcottelab.org/MSpresso/).