Optimal Precursor Ion Selection for LC-MALDI MS/MS
News Feb 26, 2013
Liquid chromatography mass spectrometry (LC-MS) maps in shotgun proteomics are often too complex to select every detected peptide signal for fragmentation by tandem mass spectrometry (MS/MS).Standard methods for precursor ion selection, commonly based on data dependent acquisition, select highly abundant peptide signals in each spectrum. However, these approaches produce redundant information and are biased towards high-abundance proteins.
We present two algorithms for inclusion list creation that formulate precursor ion selection as an optimization problem. Given an LC-MS map, the first approach maximizes the number of selected precursors given constraints such as a limited number of acquisitions per RT fraction. Second, we introduce a protein sequence-based inclusion list that can be used to monitor proteins of interest. Given only the protein sequences, we create an inclusion list that optimally covers the whole protein set. Additionally, we propose an iterative precursor ion selection that aims at reducing the redundancy obtained with data dependent LC-MS/MS. We overcome the risk of erroneous assignments by including methods for retention time and proteotypicity predictions. We show that our method identifies a set of proteins requiring fewer precursors than standard approaches. Thus, it is well suited for precursor ion selection in experiments with limited sample amount or analysis time.
We present three approaches to precursor ion selection with LC-MALDI MS/MS. Using a well defined protein standard and a complex human cell lysate, we demonstrate that our methods out perform standard approaches. Our algorithms are implemented as part of OpenMS and are available under www.openms.de.
The article is published online in the journal BMC Bioinformatics and is free to access.
Arrow Poison Potential Male Birth ControlNews
Women have many options for oral contraceptives that are safe, effective and reversible, but despite decades of research, men have none. Now, scientists report a rat study that shows they finally have a good lead for a male birth control pill. It's based on ouabain, a plant extract that African warriors and hunters traditionally used as a heart-stopping poison on their arrows.READ MORE
Robust Multiplex Mass Spectrometric Assay for Screening Small-Molecule InhibitorsNews
A new original research article presents a fast, sensitive, and robust methodology for screening small molecule inhibitors against CD73/Ecto-5'-Nucleotidase, a promising target for developing anti-cancer drugs.READ MORE