Statistical detection of differentially abundant ions in mass spectrometry-based imaging experiments with complex designs
Abstract
Here, Mass Spectrometry Imaging (MSI) characterizes changes in chemical composition between regions of biological samples such as tissues. One goal of statistical analysis of MSI experiments is class comparison, i.e. determining analytes that change in abundance between conditions more systematically than as expected by random variation. To reach accurate and reproducible conclusions, statistical analysis must appropriately reflect the initial research question, the design of the MSI experiment, and all the associated sources of variation. This manuscript highlights the importance of following these general statistical principles. Using the example of two case studies with complex experimental designs, and with different strategies of data acquisition, we demonstrate the extent to which choices made at key points of this workflow impact the results, and provide suggestions for appropriate design and analysis of MSI experiments that aim at detecting differentially abundant analytes.
- Authors:
-
- Northeastern Univ., Boston, MA (United States)
- Purdue Univ., West Lafayette, IN (United States); Northeastern Univ., Boston, MA (United States)
- Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
- Uppsala Univ., Uppsala (Sweden)
- Oregon Health & Science Univ., Portland, OR (United States)
- Purdue Univ., West Lafayette, IN (United States)
- Publication Date:
- Research Org.:
- Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1468953
- Report Number(s):
- PNNL-SA-128968
Journal ID: ISSN 1387-3806; PII: S1387380617303615
- Grant/Contract Number:
- ES024229-01; AC05-76RL01830
- Resource Type:
- Journal Article: Accepted Manuscript
- Journal Name:
- International Journal of Mass Spectrometry
- Additional Journal Information:
- Journal Volume: 437; Journal ID: ISSN 1387-3806
- Publisher:
- Elsevier
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; Mass spectrometry imaging; Nano-DESI MSI; DESI MSI; Experimental design; Statistical analysis; Spatial statistics
Citation Formats
Bemis, Kylie A., Guo, Dan, Harry, April J., Thomas, Mathew, Lanekoff, Ingela, Stenzel-Poore, Mary P., Stevens, Susan L., Laskin, Julia, and Vitek, Olga. Statistical detection of differentially abundant ions in mass spectrometry-based imaging experiments with complex designs. United States: N. p., 2018.
Web. doi:10.1016/j.ijms.2018.07.006.
Bemis, Kylie A., Guo, Dan, Harry, April J., Thomas, Mathew, Lanekoff, Ingela, Stenzel-Poore, Mary P., Stevens, Susan L., Laskin, Julia, & Vitek, Olga. Statistical detection of differentially abundant ions in mass spectrometry-based imaging experiments with complex designs. United States. https://doi.org/10.1016/j.ijms.2018.07.006
Bemis, Kylie A., Guo, Dan, Harry, April J., Thomas, Mathew, Lanekoff, Ingela, Stenzel-Poore, Mary P., Stevens, Susan L., Laskin, Julia, and Vitek, Olga. 2018.
"Statistical detection of differentially abundant ions in mass spectrometry-based imaging experiments with complex designs". United States. https://doi.org/10.1016/j.ijms.2018.07.006. https://www.osti.gov/servlets/purl/1468953.
@article{osti_1468953,
title = {Statistical detection of differentially abundant ions in mass spectrometry-based imaging experiments with complex designs},
author = {Bemis, Kylie A. and Guo, Dan and Harry, April J. and Thomas, Mathew and Lanekoff, Ingela and Stenzel-Poore, Mary P. and Stevens, Susan L. and Laskin, Julia and Vitek, Olga},
abstractNote = {Here, Mass Spectrometry Imaging (MSI) characterizes changes in chemical composition between regions of biological samples such as tissues. One goal of statistical analysis of MSI experiments is class comparison, i.e. determining analytes that change in abundance between conditions more systematically than as expected by random variation. To reach accurate and reproducible conclusions, statistical analysis must appropriately reflect the initial research question, the design of the MSI experiment, and all the associated sources of variation. This manuscript highlights the importance of following these general statistical principles. Using the example of two case studies with complex experimental designs, and with different strategies of data acquisition, we demonstrate the extent to which choices made at key points of this workflow impact the results, and provide suggestions for appropriate design and analysis of MSI experiments that aim at detecting differentially abundant analytes.},
doi = {10.1016/j.ijms.2018.07.006},
url = {https://www.osti.gov/biblio/1468953},
journal = {International Journal of Mass Spectrometry},
issn = {1387-3806},
number = ,
volume = 437,
place = {United States},
year = {Fri Aug 03 00:00:00 EDT 2018},
month = {Fri Aug 03 00:00:00 EDT 2018}
}
Web of Science
Works referenced in this record:
A concise review of mass spectrometry imaging
journal, June 2010
- Amstalden van Hove, Erika R.; Smith, Donald F.; Heeren, Ron M. A.
- Journal of Chromatography A, Vol. 1217, Issue 25
A critical evaluation of the current state-of-the-art in quantitative imaging mass spectrometry
journal, November 2013
- Ellis, Shane R.; Bruinen, Anne L.; Heeren, Ron M. A.
- Analytical and Bioanalytical Chemistry, Vol. 406, Issue 5
Histology by Mass Spectrometry: Label-Free Tissue Characterization Obtained from High-Accuracy Bioanalytical Imaging
journal, April 2010
- Römpp, Andreas; Guenther, Sabine; Schober, Yvonne
- Angewandte Chemie International Edition, Vol. 49, Issue 22
Mass spectrometry imaging as a tool for surgical decision-making: Intraoperative mass spectrometry
journal, November 2013
- Calligaris, David; Norton, Isaiah; Feldman, Daniel R.
- Journal of Mass Spectrometry, Vol. 48, Issue 11
Desorption electrospray ionization mass spectrometry: Imaging drugs and metabolites in tissues
journal, August 2008
- Wiseman, J. M.; Ifa, D. R.; Zhu, Y.
- Proceedings of the National Academy of Sciences, Vol. 105, Issue 47
Mass spectrometry imaging for drug distribution studies
journal, August 2012
- Prideaux, Brendan; Stoeckli, Markus
- Journal of Proteomics, Vol. 75, Issue 16
Experimental Models to Study Drug Distributions in Tissue Using MALDI Mass Spectrometry Imaging
journal, November 2013
- Végvári, Ákos; Fehniger, Thomas E.; Rezeli, Melinda
- Journal of Proteome Research, Vol. 12, Issue 12
Imaging mass spectrometry of proteins and peptides: 3D volume reconstruction
journal, January 2008
- Andersson, Malin; Groseclose, M. Reid; Deutch, Ariel Y.
- Nature Methods, Vol. 5, Issue 1
Integrating spatially resolved three-dimensional MALDI IMS with in vivo magnetic resonance imaging
journal, December 2007
- Sinha, Tuhin K.; Khatib-Shahidi, Sheerin; Yankeelov, Thomas E.
- Nature Methods, Vol. 5, Issue 1
Connecting imaging mass spectrometry and magnetic resonance imaging-based anatomical atlases for automated anatomical interpretation and differential analysis
journal, July 2017
- Verbeeck, Nico; Spraggins, Jeffrey M.; Murphy, Monika J. M.
- Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Vol. 1865, Issue 7
Molecular Imaging of Biological Samples: Localization of Peptides and Proteins Using MALDI-TOF MS
journal, December 1997
- Caprioli, Richard M.; Farmer, Terry B.; Gile, Jocelyn
- Analytical Chemistry, Vol. 69, Issue 23
Development of capabilities for imaging mass spectrometry under ambient conditions with desorption electrospray ionization (DESI)
journal, January 2007
- Ifa, Demian R.; Wiseman, Justin M.; Song, Qingyu
- International Journal of Mass Spectrometry, Vol. 259, Issue 1-3
Tissue Imaging Using Nanospray Desorption Electrospray Ionization Mass Spectrometry
journal, December 2011
- Laskin, Julia; Heath, Brandi S.; Roach, Patrick J.
- Analytical Chemistry, Vol. 84, Issue 1
Imaging mass spectrometry statistical analysis
journal, August 2012
- Jones, Emrys A.; Deininger, Sören-Oliver; Hogendoorn, Pancras C. W.
- Journal of Proteomics, Vol. 75, Issue 16
MALDI imaging mass spectrometry: statistical data analysis and current computational challenges
journal, November 2012
- Alexandrov, Theodore
- BMC Bioinformatics, Vol. 13, Issue S16
Forensic applications of desorption electrospray ionisation mass spectrometry (DESI-MS)
journal, March 2013
- Morelato, Marie; Beavis, Alison; Kirkbride, Paul
- Forensic Science International, Vol. 226, Issue 1-3
Forensic Chemistry and Ambient Mass Spectrometry: A Perfect Couple Destined for a Happy Marriage?
journal, February 2016
- Correa, Deleon N.; Santos, Jandyson M.; Eberlin, Livia S.
- Analytical Chemistry, Vol. 88, Issue 5
Statistical Design of Quantitative Mass Spectrometry-Based Proteomic Experiments
journal, March 2009
- Oberg, Ann L.; Vitek, Olga
- Journal of Proteome Research, Vol. 8, Issue 5
Analyzing Liposomal Drug Delivery Systems in Three-Dimensional Cell Culture Models Using MALDI Imaging Mass Spectrometry
journal, July 2017
- Lukowski, Jessica K.; Weaver, Eric M.; Hummon, Amanda B.
- Analytical Chemistry, Vol. 89, Issue 16
Mass spectrometry imaging identifies palmitoylcarnitine as an immunological mediator during Salmonella Typhimurium infection
journal, June 2017
- Hulme, Heather E.; Meikle, Lynsey M.; Wessel, Hannah
- Scientific Reports, Vol. 7, Issue 1
Multivariate statistical differentiation of renal cell carcinomas based on lipidomic analysis by ambient ionization imaging mass spectrometry
journal, October 2010
- Dill, Allison L.; Eberlin, Livia S.; Zheng, Cheng
- Analytical and Bioanalytical Chemistry, Vol. 398, Issue 7-8
Processing MALDI mass spectra to improve mass spectral direct tissue analysis
journal, February 2007
- Norris, Jeremy L.; Cornett, Dale S.; Mobley, James A.
- International Journal of Mass Spectrometry, Vol. 260, Issue 2-3
Automated Platform for High-Resolution Tissue Imaging Using Nanospray Desorption Electrospray Ionization Mass Spectrometry
journal, September 2012
- Lanekoff, Ingela; Heath, Brandi S.; Liyu, Andrey
- Analytical Chemistry, Vol. 84, Issue 19
Feature extraction and quantification for mass spectrometry in biomedical applications using the mean spectrum
journal, January 2005
- Morris, J. S.; Coombes, K. R.; Koomen, J.
- Bioinformatics, Vol. 21, Issue 9
Normalization in MALDI-TOF imaging datasets of proteins: practical considerations
journal, April 2011
- Deininger, Sören-Oliver; Cornett, Dale S.; Paape, Rainer
- Analytical and Bioanalytical Chemistry, Vol. 401, Issue 1
Robust Data Processing and Normalization Strategy for MALDI Mass Spectrometric Imaging
journal, January 2012
- Fonville, Judith M.; Carter, Claire; Cloarec, Olivier
- Analytical Chemistry, Vol. 84, Issue 3
Chemo-informatic strategy for imaging mass spectrometry-based hyperspectral profiling of lipid signatures in colorectal cancer
journal, January 2014
- Veselkov, K. A.; Mirnezami, R.; Strittmatter, N.
- Proceedings of the National Academy of Sciences, Vol. 111, Issue 3
Imaging Nicotine in Rat Brain Tissue by Use of Nanospray Desorption Electrospray Ionization Mass Spectrometry
journal, December 2012
- Lanekoff, Ingela; Thomas, Mathew; Carson, James P.
- Analytical Chemistry, Vol. 85, Issue 2
Matrix effects in biological mass spectrometry imaging: identification and compensation
journal, January 2014
- Lanekoff, Ingela; Stevens, Susan L.; Stenzel-Poore, Mary P.
- The Analyst, Vol. 139, Issue 14
EXIMS: an improved data analysis pipeline based on a new peak picking method for EXploring Imaging Mass Spectrometry data
journal, June 2015
- Wijetunge, Chalini D.; Saeed, Isaam; Boughton, Berin A.
- Bioinformatics, Vol. 31, Issue 19
Gastric Cancer-Specific Protein Profile Identified Using Endoscopic Biopsy Samples via MALDI Mass Spectrometry
journal, August 2010
- Kim, Hark Kyun; Reyzer, Michelle L.; Choi, Il Ju
- Journal of Proteome Research, Vol. 9, Issue 8
Partial least squares for discrimination
journal, January 2003
- Barker, Matthew; Rayens, William
- Journal of Chemometrics, Vol. 17, Issue 3
Integrating Histology and Imaging Mass Spectrometry
journal, January 2004
- Chaurand, Pierre; Schwartz, Sarah A.; Billheimer, Dean
- Analytical Chemistry, Vol. 76, Issue 4
Using the general linear mixed model to analyse unbalanced repeated measures and longitudinal data
journal, October 1997
- Cnaan, Avital; Laird, Nan M.; Slasor, Peter
- Statistics in Medicine, Vol. 16, Issue 20
Spatial Autocorrelation in Mass Spectrometry Imaging
journal, May 2016
- Cassese, Alberto; Ellis, Shane R.; Ogrinc Potočnik, Nina
- Analytical Chemistry, Vol. 88, Issue 11
Top-Down Proteomics with Mass Spectrometry Imaging: A Pilot Study towards Discovery of Biomarkers for Neurodevelopmental Disorders
journal, April 2014
- Ye, Hui; Mandal, Rakesh; Catherman, Adam
- PLoS ONE, Vol. 9, Issue 4
Probabilistic Segmentation of Mass Spectrometry (MS) Images Helps Select Important Ions and Characterize Confidence in the Resulting Segments
journal, May 2016
- Bemis, Kyle D.; Harry, April; Eberlin, Livia S.
- Molecular & Cellular Proteomics, Vol. 15, Issue 5
Cardinal : an R package for statistical analysis of mass spectrometry-based imaging experiments: Fig. 1.
journal, March 2015
- Bemis, Kyle D.; Harry, April; Eberlin, Livia S.
- Bioinformatics, Vol. 31, Issue 14
Statistical significance for genomewide studies
journal, July 2003
- Storey, J. D.; Tibshirani, R.
- Proceedings of the National Academy of Sciences, Vol. 100, Issue 16, p. 9440-9445
Sequencing technology does not eliminate biological variability
journal, July 2011
- Hansen, Kasper D.; Wu, Zhijin; Irizarry, Rafael A.
- Nature Biotechnology, Vol. 29, Issue 7
False-Positive Psychology: Undisclosed Flexibility in Data Collection and Analysis Allows Presenting Anything as Significant
journal, October 2011
- Simmons, Joseph P.; Nelson, Leif D.; Simonsohn, Uri
- Psychological Science, Vol. 22, Issue 11
Works referencing / citing this record:
Colocalization Features for Classification of Tumors Using Desorption Electrospray Ionization Mass Spectrometry Imaging
journal, May 2019
- Inglese, Paolo; Correia, Gonçalo; Pruski, Pamela
- Analytical Chemistry
Colocalization Features for Classification of Tumors Using Desorption Electrospray Ionization Mass Spectrometry Imaging.
text, January 2019
- Inglese, Paolo; Correia, Gonçalo; Pruski, Pamela
- Apollo - University of Cambridge Repository