Label-free quantitative proteomics using large peptide data sets generated by nanoflow liquid chromatography and mass spectrometry

Mol Cell Proteomics. 2006 Jul;5(7):1338-47. doi: 10.1074/mcp.T500039-MCP200. Epub 2006 Mar 21.

Abstract

We developed an integrated platform consisting of machinery and software modules that can apply vast amounts of data generated by nanoflow LC-MS to differential protein expression analyses. Unlabeled protein samples were completely digested with modified trypsin and separated by low speed (200 nl/min) one-dimensional HPLC. Mass spectra were obtained every 1 s by using the survey mode of a hybrid Q-TOF mass spectrometer and displayed in a two-dimensional plane with m/z values along the x axis, and retention time was displayed along the y axis. The time jitter of nano-LC was adjusted using newly developed software based on a dynamic programming algorithm. The comprehensiveness (60,000-160,000 peaks above the predetermined threshold detectable in 60-microg cell protein samples), reproducibility (average coefficient of variance of 0.35-0.39 and correlation coefficient of over 0.92 between duplicates), and accurate quantification with a wide dynamic range (over 10(3)) of our platform warrant its application to various types of experimental and translational proteomics.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Actinin / analysis
  • Actinin / metabolism
  • Automation / instrumentation
  • Blood Cells / chemistry
  • Cell Movement
  • Chromatography, High Pressure Liquid / methods*
  • Colorectal Neoplasms / metabolism
  • Diagnostic Imaging
  • Doxycycline / pharmacology
  • Gene Expression
  • Genes, Reporter
  • Humans
  • Mass Spectrometry / methods*
  • Microfilament Proteins / analysis
  • Microfilament Proteins / metabolism
  • Microfluidic Analytical Techniques / instrumentation*
  • Pancreatic Neoplasms / metabolism
  • Peptide Fragments / chemistry*
  • Proteome / analysis
  • Proteomics / instrumentation
  • Proteomics / methods*
  • Software
  • Transfection
  • Tumor Cells, Cultured

Substances

  • ACTN4 protein, human
  • Microfilament Proteins
  • Peptide Fragments
  • Proteome
  • Actinin
  • Doxycycline