rMSIcleanup: An open-source tool for matrix-related peak annotation in mass spectrometry imaging and its application to silver-assisted laser desorption/ionization

Abstract

14Mass spectrometry imaging (MSI) has become a mature, widespread analytical technique to 15 perform non-targeted spatial metabolomics. However, the compounds used to promote 16 desorption and ionization of the analyte during acquisition cause spectral interferences in the 17 low mass range that hinder downstream data processing in metabolomics applications. Thus, it 18 is advisable to annotate and remove matrix-related peaks to reduce the number of redundant 19and non-biologically-relevant variables in the dataset. We have developed rMSIcleanup, an 20 open-source R package to annotate and remove matrix-related signals based on its chemical 21 formula and the spatial distribution of its ions. To validate the annotation method, rMSIcleanup 22was challenged with several images acquired using silver-assisted laser desorption ionization 23 MSI (AgLDI MSI). The algorithm was able to correctly classify m/z signals related to silver clusters. 24Visual exploration of the data using Principal Component Analysis (PCA) demonstrated that 25 annotation and removal of matrix-related signals improved spectral data post-processing. The 26 results highlight the need for including matrix-related peak annotation tools such as 27 rMSIcleanup in MSI workflows. 28

Surface‐assisted laser desorption/ionization mass spectrometry imaging: A review

“…The SALDI mass spectra of the samples can also be internally mass calibrated using the nanosubstrate ions or cluster ions (e.g., Au n +/− and Ag n +/− clusters) (Kolárova et al, 2017;Prysiazhnyi et al, 2019;Ràfols et al, 2018 (Baquer et al, 2020). In this context, silver-based nanosubstrates are particularly adapted thanks to the two abundant and stable natural isotopes of silver, 107 Ag (51.839%) and 109 Ag (48.161%), which can be distinguished in the mass spectrum.…”

“…Pure metal: Au (Chau et al, 2017 ; Dufresne et al, 2016 ; Hansen et al, 2019 ; Rafols et al 2018 ; Tang et al, 2010 , 2011a , 2011b ), Ag (Baquer et al, 2020 ; Dufresne et al, 2013 ; Hansen et al, 2019 ; Lauzon et al, 2015 ; Yang et al, 2020 ), Pt (Hansen et al, 2019 ; Ozawa et al, 2016 ), Cu (Hansen et al, 2019 ), Ti (Hansen et al, 2019 ), Ni (Hansen et al, 2019 );…”

“…Nevertheless, the ionization of the LDI‐assisting substrate in SALDI‐MSI does not significantly increase the chemical background of the spectra in the low m/z values, which is not the case in MALDI‐MS. Moreover, recently developed chemometric approaches enable to annotate the signals attributed to the nanosubstrate in SALDI‐MSI and thus, to clean up the mass spectra from the LDI‐assisting substrate signals (Baquer et al, 2020 ). In this context, silver‐based nanosubstrates are particularly adapted thanks to the two abundant and stable natural isotopes of silver, 107 Ag (51.839%) and 109 Ag (48.161%), which can be distinguished in the mass spectrum.…”

“…Moreover, abnormal Na + and K + distributions may result from an alteration of the ATP metabolism underlying a disease (Guan et al, 2018 ). However, close attention has to be paid to the SALDI‐MSI data processing due to the high heterogeneity in the formation of adducts between biological compounds from the sample and silver cations (Baquer et al, 2020 ).…”

“…Summary of the different types of samples analyzed by SALDI-MSISample type ReferencesMurine brainAgeta et al (2009);Baquer et al (2020);Cha and Yeung (2007);Dufresne et al (2013);Fincher et al (2019aFincher et al ( , 2020b; Goto-Inoue et al (2010); Guan et al (2018); Iakab et al (2020); Kim et al (2011); Lee et al (2012); Lopez de Laorden et al (2015); Muller et al (2017); Müller et al (2020); Patti et al (2010a, 2010b); Rafols et al (2018); Shrivas et al (2011); Stopka et al (2016); Taira et al (2008); Wu et al (2017); Yanes et al (2009); Yang et al (2020); Zhou et al (2017) Murine kidney Baquer et al (2020); Chau et al (2017); Cheng et al (2019a, 2019b); Dufresne et al (2013); Iakab et al (2020); Krasny et al (2015); Stopka et al (2016) Tata et al (2014); Vidova et al . (2016); Guinan et al (2015a, 2015c); Iakab et al (2020); Lauzon et al (2015); Niziol and Ruman (2013b); Sekula et al (2015a, 2015b); Schnapp et al (2016); Skriba and Havlicek (2018); Tang et al (2010); Yang et al (2019); Wang et al (2020b) Tumoral and cancerous samples Huang et al 2015; Morosi et al (2013); Niziol et al (2016, 2020); O'Brien et al (2013); Rudd et al (2019); Tang et al (2011b); Tata et al (2012); Tseng et al (2017); Zhou et al (2017) Flowers Dutkiewicz et al (2019); Jun et al (2010); Niziol and Ruman (2013b); Patti et al (2010b); Wang et al (2020) Leaves Ozawa et al (2016) Fruits De Oliveira et al (2014); Niziol et al (2019); Zhang et al (2007) Roots and bulbs Hansen et al (2019); Jun et al (2010); Misiorek et al (2017); Sekula et al (2015a); Shiono and Taira (2020) Stems Dutkiewicz et al (2019); Niziol and Ruman (2013b); Patti et al (2010b) Seeds Hansen et al (2019) Bacteria and fungi Chen et al (2018); Dutkiewicz et al (2019) Cells and embryos Ferreira et al (2014); Liu et al (2007); McLaughlin et al (2020); Stopka and Vertes (Ronci et al (2012); Rudd et al (2015) T A B L E 4 Summary of the deposition/utilization of the nanosubstrates…”