A mathematical framework for interpreting the molecular code of the tumor suppressor p53
Final Report Abstract
Post-translational modifications (PTMs) on proteins regulate protein structures and functions. A single protein molecule can possess multiple modification sites that can accommodate various PTM types, leading to a variety of different patterns, or combinat ions of PTMs, on that protein. Different PTM patterns can give rise to distinct biological functions. To facilitate the study of multiple PTMs, top-down mass spectrometry (MS) has proven to be a useful tool to measure the mass of intact proteins, thereby enabling even widely separated PTMs to be assigned to the same protein molecule and allowing determination of how many PTMs are attached to a single protein. We developed a Python module called MSModDetector that studies PTM patterns from individual ion mass spectrometry (I2MS) data. I2MS is an intact protein mass spectrometry approach that generates true mass spectra without the need to infer charge states. Th e algorithm first detects and quantifies mass shifts for a protein of interest and subsequently infers potential PTM patterns using linear programming. The algorithm is evaluated on simulated I2MS data and experimental I2MS data for the tumor suppressor pr otein p53. We show that MSModDetector is a useful tool for comparing a protein's PTM pattern landscape across different conditions. An improved analysis of PTM patterns will enable a deeper understanding of PTM-regulated cellular processes.
Publications
-
MSModDetector: A Tool for Detecting Mass Shifts and Post-Translational Modifications in Individual Ion Mass Spectrometry Data.
Faizi, Marjan; Fellers, Ryan T.; Lu, Dan; Drown, Bryon S.; Jambhekar, Ashwini; Lahav, Galit; Kelleher, Neil L. & Gunawardena, Jeremy
