Abstract
Conventional mass spectrometry image preprocessing methods used for denoising, such as the Savitzky-Golay smoothing or discrete wavelet transformation, typically do not only remove noise but also weak signals. Recently, memory-efficient principal component analysis (PCA) in conjunction with random projections (RP) has been proposed for reversible compression and analysis of large mass spectrometry imaging datasets. It considers single-pixel spectra in their local context and consequently offers the prospect of using information from the spectra of adjacent pixels for denoising or signal enhancement. However, little systematic analysis of key RP-PCA parameters has been reported so far, and the utility and validity of this method for context-dependent enhancement of known medically or pharmacologically relevant weak analyte signals in linear-mode matrix-assisted laser desorption/ionization (MALDI) mass spectra has not been explored yet. Here, we investigate MALDI imaging datasets from mouse models of Alzheimer’s disease and gastric cancer to systematically assess the importance of selecting the right number of random projections k and of principal components (PCs) L for reconstructing reproducibly denoised images after compression. We provide detailed quantitative data for comparison of RP-PCA-denoising with the Savitzky-Golay and wavelet-based denoising in these mouse models as a resource for the mass spectrometry imaging community. Most importantly, we demonstrate that RP-PCA preprocessing can enhance signals of low-intensity amyloid-β peptide isoforms such as Aβ1-26 even in sparsely distributed Alzheimer’s β-amyloid plaques and that it enables enhanced imaging of multiply acetylated histone H4 isoforms in response to pharmacological histone deacetylase inhibition in vivo. We conclude that RP-PCA denoising may be a useful preprocessing step in biomarker discovery workflows.
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References
Gessel MM, Norris JL, Caprioli RM (2014) MALDI imaging mass spectrometry: spatial molecular analysis to enable a new age of discovery. J Proteome 107C:71–82. doi:10.1016/j.jprot.2014.03.021
Jones EA, Deininger SO, Hogendoorn PC, Deelder AM, McDonnell LA (2012) Imaging mass spectrometry statistical analysis. J Proteome 75(16):4962–4989. doi:10.1016/j.jprot.2012.06.014
Ellis SR, Bruinen AL, Heeren RM (2014) A critical evaluation of the current state-of-the-art in quantitative imaging mass spectrometry. Anal Bioanal Chem 406(5):1275–1289. doi:10.1007/s00216-013-7478-9
Alexandrov T (2012) MALDI imaging mass spectrometry: statistical data analysis and current computational challenges. BMC Bioinforma 13(Suppl 16):S11. doi:10.1186/1471-2105-13-S16-S11
Trede D, Kobarg JH, Oetjen J, Thiele H, Maass P, Alexandrov T (2012) On the importance of mathematical methods for analysis of MALDI-imaging mass spectrometry data. J Integr Bioinforma 9(1):189. doi:10.2390/biecoll-jib-2012-189
Norris JL, Cornett DS, Mobley JA, Andersson M, Seeley EH, Chaurand P, Caprioli RM (2007) Processing MALDI mass spectra to improve mass spectral direct tissue analysis. Int J Mass Spectrom 260(2–3):212–221. doi:10.1016/j.ijms.2006.10.005
McDonnell LA, van Remoortere A, van Zeijl RJ, Deelder AM (2008) Mass spectrometry image correlation: quantifying colocalization. J Proteome Res 7(8):3619–3627. doi:10.1021/pr800214d
McDonnell LA, van Remoortere A, de Velde N, van Zeijl RJ, Deelder AM (2010) Imaging mass spectrometry data reduction: automated feature identification and extraction. J Am Soc Mass Spectrom 21(12):1969–1978. doi:10.1016/j.jasms.2010.08.008
Alexandrov T, Kobarg JH (2011) Efficient spatial segmentation of large imaging mass spectrometry datasets with spatially aware clustering. Bioinformatics 27(13):i230–i238. doi:10.1093/bioinformatics/btr246
Alexandrov T, Becker M, Deininger SO, Ernst G, Wehder L, Grasmair M, von Eggeling F, Thiele H, Maass P (2010) Spatial segmentation of imaging mass spectrometry data with edge-preserving image denoising and clustering. J Proteome Res 9(12):6535–6546. doi:10.1021/pr100734z
Jardin-Mathe O, Bonnel D, Franck J, Wisztorski M, Macagno E, Fournier I, Salzet M (2008) MITICS (MALDI Imaging Team Imaging Computing System): a new open source mass spectrometry imaging software. J Proteome 71(3):332–345. doi:10.1016/j.jprot.2008.07.004
Hanselmann M, Kothe U, Kirchner M, Renard BY, Amstalden ER, Glunde K, Heeren RM, Hamprecht FA (2009) Toward digital staining using imaging mass spectrometry and random forests. J Proteome Res 8(7):3558–3567. doi:10.1021/pr900253y
Savitzky A, Golay MJE (1964) Smoothing and differentiation of data by simplified least squares procedures. Anal Chem 36(8):1627–1639. doi:10.1021/ac60214a047
Vivo-Truyols G, Schoenmakers PJ (2006) Automatic selection of optimal Savitzky-Golay smoothing. Anal Chem 78(13):4598–4608. doi:10.1021/ac0600196
Yang C, He Z, Yu W (2009) Comparison of public peak detection algorithms for MALDI mass spectrometry data analysis. BMC Bioinforma 10:4. doi:10.1186/1471-2105-10-4
Kallback P, Shariatgorji M, Nilsson A, Andren PE (2012) Novel mass spectrometry imaging software assisting labeled normalization and quantitation of drugs and neuropeptides directly in tissue sections. J Proteome 75(16):4941–4951. doi:10.1016/j.jprot.2012.07.034
van de Plas R, de Moor B, Waelkens E (2008) Discrete wavelet transform-based multivariate exploration of tissue via imaging mass spectrometry. Proceedings of the 23rd annual ACM symposium on applied computing 1307–1308. doi: 10.1145/1363686.1363989
Alexandrov T, Decker J, Mertens B, Deelder AM, Tollenaar RA, Maass P, Thiele H (2009) Biomarker discovery in MALDI-TOF serum protein profiles using discrete wavelet transformation. Bioinformatics 25(5):643–649. doi:10.1093/bioinformatics/btn662
Lagarrigue M, Alexandrov T, Dieuset G, Perrin A, Lavigne R, Baulac S, Thiele H, Martin B, Pineau C (2012) New analysis workflow for MALDI imaging mass spectrometry: application to the discovery and identification of potential markers of childhood absence epilepsy. J Proteome Res 11(11):5453–5463. doi:10.1021/pr3006974
Morris JS, Coombes KR, Koomen J, Baggerly KA, Kobayashi R (2005) Feature extraction and quantification for mass spectrometry in biomedical applications using the mean spectrum. Bioinformatics 21(9):1764–1775. doi:10.1093/bioinformatics/bti254
Coombes KR, Tsavachidis S, Morris JS, Baggerly KA, Hung MC, Kuerer HM (2005) Improved peak detection and quantification of mass spectrometry data acquired from surface-enhanced laser desorption and ionization by denoising spectra with the undecimated discrete wavelet transform. Proteomics 5(16):4107–4117. doi:10.1002/pmic.200401261
Mostacci E, Truntzer C, Cardot H, Ducoroy P (2010) Multivariate denoising methods combining wavelets and principal component analysis for mass spectrometry data. Proteomics 10(14):2564–2572. doi:10.1002/pmic.200900185
McCombie G, Staab D, Stoeckli M, Knochenmuss R (2005) Spatial and spectral correlations in MALDI mass spectrometry images by clustering and multivariate analysis. Anal Chem 77(19):6118–6124. doi:10.1021/ac051081q
Palmer AD, Bunch J, Styles IB (2013) Randomized approximation methods for the efficient compression and analysis of hyperspectral data. Anal Chem 85(10):5078–5086. doi:10.1021/ac400184g
Halko MA, Datta A, Plow EB, Scaturro J, Bikson M, Merabet LB (2011) Neuroplastic changes following rehabilitative training correlate with regional electrical field induced with tDCS. Neuroimage 57(3):885–891. doi:10.1016/j.neuroimage.2011.05.026
Dawson MA, Kouzarides T (2012) Cancer epigenetics: from mechanism to therapy. Cell 150(1):12–27. doi:10.1016/j.cell.2012.06.013
Bantscheff M, Hopf C, Savitski MM, Dittmann A, Grandi P, Michon AM, Schlegl J, Abraham Y, Becher I, Bergamini G, Boesche M, Delling M, Dumpelfeld B, Eberhard D, Huthmacher C, Mathieson T, Poeckel D, Reader V, Strunk K, Sweetman G, Kruse U, Neubauer G, Ramsden NG, Drewes G (2011) Chemoproteomics profiling of HDAC inhibitors reveals selective targeting of HDAC complexes. Nat Biotechnol 29(3):255–265. doi:10.1038/nbt.1759
Munteanu B, Meyer B, von Reitzenstein C, Burgermeister E, Bog S, Pahl A, Ebert MP, Hopf C (2014) Label-free in situ monitoring of histone deacetylase drug target engagement by matrix-assisted laser desorption ionization-mass spectrometry biotyping and imaging. Anal Chem 86(10):4642–4647. doi:10.1021/ac500038j
Van Broeck B, Chen JM, Treton G, Desmidt M, Hopf C, Ramsden N, Karran E, Mercken M, Rowley A (2011) Chronic treatment with a novel gamma-secretase modulator, JNJ-40418677, inhibits amyloid plaque formation in a mouse model of Alzheimer’s disease. Br J Pharmacol 163(2):375–389. doi:10.1111/j.1476-5381.2011.01207.x
Golde TE, Koo EH, Felsenstein KM, Osborne BA, Miele L (2013) Gamma-Secretase inhibitors and modulators. Biochim Biophys Acta 1828(12):2898–2907. doi:10.1016/j.bbamem.2013.06.005
Oakley H, Cole SL, Logan S, Maus E, Shao P, Craft J, Guillozet-Bongaarts A, Ohno M, Disterhoft J, Van Eldik L, Berry R, Vassar R (2006) Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer’s disease mutations: potential factors in amyloid plaque formation. J Neurosci 26(40):10129–10140. doi:10.1523/JNEUROSCI. 1202-06.2006
Deininger SO, Cornett DS, Paape R, Becker M, Pineau C, Rauser S, Walch A, Wolski E (2011) Normalization in MALDI-TOF imaging datasets of proteins: practical considerations. Anal Bioanal Chem 401(1):167–181. doi:10.1007/s00216-011-4929-z
Moore BD, Chakrabarty P, Levites Y, Kukar TL, Baine AM, Moroni T, Ladd TB, Das P, Dickson DW, Golde TE (2012) Overlapping profiles of Abeta peptides in the Alzheimer’s disease and pathological aging brains. Alzheimers Res Ther 4(3):18. doi:10.1186/alzrt121
Ashby FG (2011) Statistical analysis of fMRI data. MIT Press, Cambridge, pp 254–255. ISBN 0-262-01504-8
Race AM, Steven RT, Palmer AD, Styles IB, Bunch J (2013) Memory efficient principal component analysis for the dimensionality reduction of large mass spectrometry imaging data sets. Anal Chem 85(6):3071–3078. doi:10.1021/ac302528v
Acknowledgments
The authors thank Viola Nordström and Hermann-Josef Gröne for brains from mouse models of Alzheimer’s disease and Bogdan Munteanu for helpful discussions. This work was supported by the following grants: Baden-Württemberg Ministry of Science and Culture INST 874/2-1 LAGG (to C.H.), “ZAFH ABIMAS” by ZO IV/Landesstiftung Baden-Württemberg and the European fund for regional development (EFRE; to C.H. and B.W.), and by EU CMST COST Action TD0905: Epigenetics: Bench to Bedside (to C.H.).
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Published in the topical collection Mass Spectrometry Imaging with guest editors Andreas Römpp and Uwe Karst.
Matthias Schwartz and Björn Meyer contributed equally to this publication.
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Schwartz, M., Meyer, B., Wirnitzer, B. et al. Standardized processing of MALDI imaging raw data for enhancement of weak analyte signals in mouse models of gastric cancer and Alzheimer’s disease. Anal Bioanal Chem 407, 2255–2264 (2015). https://doi.org/10.1007/s00216-014-8356-9
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DOI: https://doi.org/10.1007/s00216-014-8356-9