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1.  Integrating shotgun proteomics and mRNA expression data to improve protein identification 
Bioinformatics  2009;25(11):1397-1403.
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 ∼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
Supplementary Information: Supplementary data website:
PMCID: PMC2682515  PMID: 19318424
2.  Src-like adaptor protein down-regulates T cell receptor (TCR)–CD3 expression by targeting TCRζ for degradation 
The Journal of Cell Biology  2005;170(2):285-294.
Src-like adaptor protein (SLAP) down-regulates expression of the T cell receptor (TCR)–CD3 complex during a specific stage of thymocyte development when the TCR repertoire is selected. Consequently, SLAP−/− thymocytes display alterations in thymocyte development. Here, we have studied the mechanism of SLAP function. We demonstrate that SLAP-deficient thymocytes have increased TCRζ chain expression as a result of a defect in TCRζ degradation. Failure to degrade TCRζ leads to an increased pool of fully assembled TCR–CD3 complexes that are capable of recycling back to the cell surface. We also provide evidence that SLAP functions in a pathway that requires the phosphorylated TCRζ chain and the Src family kinase Lck, but not ZAP-70 (ζ-associated protein of 70 kD). These studies reveal a unique mechanism by which SLAP contributes to the regulation of TCR expression during a distinct stage of thymocyte development.
PMCID: PMC2171412  PMID: 16027224

Results 1-2 (2)