Liquid chromatography coupled with mass spectrometry (LC-MS/MS) is
increasingly used for proteomic profiling of biofuids aiming at
discovery of candidate biomarkers of disease. However the clinical
utility of the technology is currently limited due to stochastic
variation, restricted dynamic range of the instruments, and
difficulties with the identification of peptide sequences
underlying LC-MS peaks. The difficulties can be partially
alleviated by developing specialized statistical methods that make
an efficient use of spectral information.
This talk will discuss two types of such methods for analysis of
LC-MS/MS profiles. First, we will characterize the statistical
properties of two algorithms, Peptide Prophet and decoy database
search, that are currently popular for peptide sequence
identification from LC-MS/MS spectra. Second, we will discuss two
approaches that combine quantitative LC-MS feature profiles and
available peptide sequence identities to infer changes in
abundance at the gene or a protein level. The approaches involve a
random-effects model popular in meta-analysis (DerSimonian and
Laird, 1986), and an
Empirical Bayes hierarchical model that provides a more realistic
representation of the data at the expense of a greater
computational effort. The methods are illustrated using computer
simulations, and using a clinical study of cardiovascular disease
where the models are judged by their ability to uncover previously
known protein biomarkers.
Brief Bio:
After completing a bachelor's and master's degrees in Econometrics
and Statistics at University of Geneva, Switzerland, Olga worked
as a biostatistician at the University Hospitals of Geneva where
she became interested in development and application of
quantitative methods in molecular biology. She moved to Purdue and
obtained a masters and PhD in Statistics under co-direction of
Chris Bailey-Kellogg and Bruce Craig. As a graduate student she
closely collaborated with biologists, chemists and computer
scientists through projects in genomics and structural biology,
statistical
consulting and an internship in a proteomics lab at Eli Lilly and
Company. After graduation she took a position of post-doctoral
associate in Ruedi Aebersold's lab at the Institute for Systems
Biology in Seattle and worked on projects in computational
proteomics. In Fall 2006 she came back to Purdue as an Assistant
Professor in Statistics and Computer Science.