Skip to main content
U.S. Department of Energy
Office of Scientific and Technical Information

Detecting differential protein abundance by combining peptide level P-values

Journal Article · · Molecular Omics
DOI:https://doi.org/10.1039/d0mo00045k· OSTI ID:1752963
 [1];  [2];  [3]
  1. Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Washington State Univ., Pullman, WA (United States)
  2. Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
  3. Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Washington State Univ., Pullman, WA (United States
The majority of methods for detecting differentially abundant proteins between samples in label-free LC-MS bottom-up proteomics experiments rely on statistically testing inferred protein abundances derived from peptide ionization intensities or averaging peptide level statistics. Here in this paper, we statistically test peptide ionization intensities directly and combine the resulting dependent P-values using the Empirical Brown's Method (EBM), avoiding error introduced through the estimation of protein abundances or summarizing test statistics. We show that on a spike-in proteomics dataset, a peptide level approach using EBM outperforms differential abundance detection using a protein level approach and several analysis workflows, including MSstats. Additionally, we demonstrate the effectiveness of this approach by detecting enriched proteins from an activity-based protein profiling dataset.
Research Organization:
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
Sponsoring Organization:
USDOE
Grant/Contract Number:
AC05-76RL01830; AC06-76RL01830
OSTI ID:
1752963
Report Number(s):
PNNL-SA--144005
Journal Information:
Molecular Omics, Journal Name: Molecular Omics Journal Issue: 6 Vol. 16; ISSN 2515-4184
Publisher:
Royal Society of ChemistryCopyright Statement
Country of Publication:
United States
Language:
English

References (18)

Combining dependent P-values journal November 2002
Thousand and one ways to quantify and compare protein abundances in label-free bottom-up proteomics journal August 2016
Multidimensional Tracking of GPCR Signaling via Peroxidase-Catalyzed Proximity Labeling journal April 2017
mapDIA: Preprocessing and statistical analysis of quantitative proteomics data from data independent acquisition mass spectrometry journal November 2015
Using Peptide-Level Proteomics Data for Detecting Differentially Expressed Proteins journal September 2015
Protein Analysis by Shotgun/Bottom-up Proteomics journal February 2013
Activity-Based Probes for Isoenzyme- and Site-Specific Functional Characterization of Glutathione S -Transferases journal November 2017
The CPTAC Data Portal: A Resource for Cancer Proteomics Research journal May 2015
MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification journal November 2008
Accurate Proteome-wide Label-free Quantification by Delayed Normalization and Maximal Peptide Ratio Extraction, Termed MaxLFQ journal June 2014
Peptide-level Robust Ridge Regression Improves Estimation, Sensitivity, and Specificity in Data-dependent Quantitative Label-free Shotgun Proteomics journal November 2015
DAnTE: a statistical tool for quantitative analysis of -omics data journal May 2008
MSstats: an R package for statistical analysis of quantitative mass spectrometry-based proteomic experiments journal May 2014
Combining dependent P- values with an empirical adaptation of Brown’s method journal September 2016
UniProt: a hub for protein information journal October 2014
Activity-Based Protein Profiling: From Enzyme Chemistry to Proteomic Chemistry journal June 2008
Multiscale mutation clustering algorithm identifies pan-cancer mutational clusters associated with pathway-level changes in gene expression journal February 2017
400: A Method for Combining Non-Independent, One-Sided Tests of Significance journal December 1975

Similar Records

Combined Statistical Analyses of Peptide Intensities and Peptide Occurrences Improves Identification of Significant Peptides from MS-based Proteomics Data
Journal Article · Mon Nov 01 00:00:00 EDT 2010 · Journal of Proteome Research, 9(11):5748-5756 · OSTI ID:1000135

Improved Quality Control Processing of Peptide-centric LC-MS Proteomics Data
Journal Article · Tue Sep 20 00:00:00 EDT 2011 · Bioinformatics · OSTI ID:1031421

Detecting Differential and Correlated Protein Expression in Label-Free Shotgun Proteomics
Journal Article · Sat Dec 31 23:00:00 EST 2005 · Journal of Proteome Research · OSTI ID:930904