PMID- 25372836
OWN - NLM
STAT- MEDLINE
DCOM- 20150629
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 11
DP  - 2014
TI  - The application of Gaussian mixture models for signal quantification in MALDI-TOF 
      mass spectrometry of peptides.
PG  - e111016
LID - 10.1371/journal.pone.0111016 [doi]
LID - e111016
AB  - Matrix assisted laser desorption/ionization time-of-flight (MALDI-TOF) coupled 
      with stable isotope standards (SIS) has been used to quantify native peptides. 
      This peptide quantification by MALDI-TOF approach has difficulties quantifying 
      samples containing peptides with ion currents in overlapping spectra. In these 
      overlapping spectra the currents sum together, which modify the peak heights and 
      make normal SIS estimation problematic. An approach using Gaussian mixtures based 
      on known physical constants to model the isotopic cluster of a known compound is 
      proposed here. The characteristics of this approach are examined for single and 
      overlapping compounds. The approach is compared to two commonly used SIS 
      quantification methods for single compound, namely Peak Intensity method and 
      Riemann sum area under the curve (AUC) method. For studying the characteristics 
      of the Gaussian mixture method, Angiotensin II, Angiotensin-2-10, and 
      Angiotenisn-1-9 and their associated SIS peptides were used. The findings 
      suggest, Gaussian mixture method has similar characteristics as the two methods 
      compared for estimating the quantity of isolated isotopic clusters for single 
      compounds. All three methods were tested using MALDI-TOF mass spectra collected 
      for peptides of the renin-angiotensin system. The Gaussian mixture method 
      accurately estimated the native to labeled ratio of several isolated angiotensin 
      peptides (5.2% error in ratio estimation) with similar estimation errors to those 
      calculated using peak intensity and Riemann sum AUC methods (5.9% and 7.7%, 
      respectively). For overlapping angiotensin peptides, (where the other two methods 
      are not applicable) the estimation error of the Gaussian mixture was 6.8%, which 
      is within the acceptable range. In summary, for single compounds the Gaussian 
      mixture method is equivalent or marginally superior compared to the existing 
      methods of peptide quantification and is capable of quantifying overlapping 
      (convolved) peptides within the acceptable margin of error.
FAU - Spainhour, John Christian G
AU  - Spainhour JC
AD  - Medical University of South Carolina, Department of Public Health Sciences, 
      Charleston, South Carolina, United States of America.
FAU - Janech, Michael G
AU  - Janech MG
AD  - Division of Nephrology, Department of Medicine, Medical University of South 
      Carolina, Charleston, South Carolina, United States of America.
FAU - Schwacke, John H
AU  - Schwacke JH
AD  - Scientific Research Corporation, North Charleston, South Carolina, United States 
      of America.
FAU - Velez, Juan Carlos Q
AU  - Velez JC
AD  - Division of Nephrology, Department of Medicine, Medical University of South 
      Carolina, Charleston, South Carolina, United States of America; Ralph H. Johnson 
      Veterans Affairs Medical Center, Charleston, South Carolina, United States of 
      America.
FAU - Ramakrishnan, Viswanathan
AU  - Ramakrishnan V
AD  - Medical University of South Carolina, Department of Public Health Sciences, 
      Charleston, South Carolina, United States of America.
LA  - eng
GR  - K08 DK080944/DK/NIDDK NIH HHS/United States
GR  - T32 GM074934/GM/NIGMS NIH HHS/United States
GR  - 5DK080944/DK/NIDDK NIH HHS/United States
GR  - 5T32GM74934-8/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20141105
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Peptides)
SB  - IM
MH  - Models, Statistical
MH  - Normal Distribution
MH  - Peptides/*chemistry
MH  - Proteomics/*methods
MH  - *Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
PMC - PMC4221630
COIS- Competing Interests: Dr. Schwacke is currently employed at Scientific Research 
      Corporation, but all work contributed to this paper was done while he was 
      employed at MUSC. This does not alter the authors' adherence to PLOS ONE policies 
      on sharing data and materials.
EDAT- 2014/11/06 06:00
MHDA- 2015/06/30 06:00
PMCR- 2014/11/05
CRDT- 2014/11/06 06:00
PHST- 2014/04/29 00:00 [received]
PHST- 2014/09/19 00:00 [accepted]
PHST- 2014/11/06 06:00 [entrez]
PHST- 2014/11/06 06:00 [pubmed]
PHST- 2015/06/30 06:00 [medline]
PHST- 2014/11/05 00:00 [pmc-release]
AID - PONE-D-14-19270 [pii]
AID - 10.1371/journal.pone.0111016 [doi]
PST - epublish
SO  - PLoS One. 2014 Nov 5;9(11):e111016. doi: 10.1371/journal.pone.0111016. 
      eCollection 2014.