Details

Autor(en) / Beteiligte

• Prakash, Amol
• Piening, Brian
• Whiteaker, Jeff
• Zhang, Heidi
• Shaffer, Scott A.
• Martin, Daniel
• Hohmann, Laura
• Cooke, Kelly
• Olson, James M.
• Hansen, Stacey
• Flory, Mark R.
• Lee, Hookeun
• Watts, Julian
• Goodlett, David R.
• Aebersold, Ruedi
• Paulovich, Amanda
• Schwikowski, Benno

Titel

Assessing Bias in Experiment Design for Large Scale Mass Spectrometry-based Quantitative Proteomics

Ist Teil von

• Molecular & cellular proteomics, 2007-10, Vol.6 (10), p.1741-1748

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2007

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Mass spectrometry-based proteomics holds great promise as a discovery tool for biomarker candidates in the early detection of diseases. Recently much emphasis has been placed upon producing highly reliable data for quantitative profiling for which highly reproducible methodologies are indispensable. The main problems that affect experimental reproducibility stem from variations introduced by sample collection, preparation, and storage protocols and LC-MS settings and conditions. On the basis of a formally precise and quantitative definition of similarity between LC-MS experiments, we have developed Chaorder, a fully automatic software tool that can assess experimental reproducibility of sets of large scale LC-MS experiments. By visualizing the similarity relationships within a set of experiments, this tool can form the basis of systematic quality control and thus help assess the comparability of mass spectrometry data over time, across different laboratories, and between instruments. Applying Chaorder to data from multiple laboratories and a range of instruments, experimental protocols, and sample complexities revealed biases introduced by the sample processing steps, experimental protocols, and instrument choices. Moreover we show that reducing bias by correcting for just a few steps, for example randomizing the run order, does not provide much gain in statistical power for biomarker discovery.