Imaging and spatially resolved mass spectrometry applications in nephrology.

Brittney L Gorman, Catelynn C Shafer, Nagarjunachary Ragi, Kumar Sharma, Elizabeth K Neumann, Christopher R Anderton
Author Information
  1. Brittney L Gorman: Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, WA, USA. ORCID
  2. Catelynn C Shafer: Department of Chemistry, University of California, Davis, Davis, CA, 95695, USA.
  3. Nagarjunachary Ragi: Center for Precision Medicine, The University of Texas Health San Antonio, San Antonio, TX, USA.
  4. Kumar Sharma: Center for Precision Medicine, The University of Texas Health San Antonio, San Antonio, TX, USA. ORCID
  5. Elizabeth K Neumann: Department of Chemistry, University of California, Davis, Davis, CA, 95695, USA.
  6. Christopher R Anderton: Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, WA, USA. Christopher.Anderton@pnnl.gov. ORCID

Abstract

The application of spatially resolved mass spectrometry (MS) and MS imaging approaches for studying biomolecular processes in the kidney is rapidly growing. These powerful methods, which enable label-free and multiplexed detection of many molecular classes across omics domains (including metabolites, drugs, proteins and protein post-translational modifications), are beginning to reveal new molecular insights related to kidney health and disease. The complexity of the kidney often necessitates multiple scales of analysis for interrogating biofluids, whole organs, functional tissue units, single cells and subcellular compartments. Various MS methods can generate omics data across these spatial domains and facilitate both basic science and pathological assessment of the kidney. Optimal processes related to sample preparation and handling for different MS applications are rapidly evolving. Emerging technology and methods, improvement of spatial resolution, broader molecular characterization, multimodal and multiomics approaches and the use of machine learning and artificial intelligence approaches promise to make these applications even more valuable in the field of nephology. Overall, spatially resolved MS and MS imaging methods have the potential to fill much of the omics gap in systems biology analysis of the kidney and provide functional outputs that cannot be obtained using genomics and transcriptomic methods.

References

  1. Chen, S. et al. Analysis of cell glycogen with quantitation and determination of branching using liquid chromatography���mass spectrometry. Anal. Chem. 95, 12884���12892 (2023). [PMID: 37584460]
  2. Heiles, S. Advanced tandem mass spectrometry in metabolomics and lipidomics ��� methods and applications. Anal. Bioanal. Chem. 413, 5927���5948 (2021). [PMID: 34142202]
  3. Ro, S. Y. et al. Native top-down mass spectrometry provides insights into the copper centers of membrane-bound methane monooxygenase. Nat. Commun. 10, 2675 (2019). [PMID: 31209220]
  4. Wohlschlager, T. et al. Native mass spectrometry combined with enzymatic dissection unravels glycoform heterogeneity of biopharmaceuticals. Nat. Commun. 9, 1713 (2018). [PMID: 29712889]
  5. Corchete, L. A. et al. Systematic comparison and assessment of RNA-seq procedures for gene expression quantitative analysis. Sci. Rep. 10, 19737 (2020). [PMID: 33184454]
  6. Larsson, L., Fris��n, J. & Lundeberg, J. Spatially resolved transcriptomics adds a new dimension to genomics. Nat. Methods 18, 15���18 (2021). [PMID: 33408402]
  7. Hussey, G. S. et al. Lipidomics and RNA sequencing reveal a novel subpopulation of nanovesicle within extracellular matrix biomaterials. Sci. Adv. 6, eaay4361
  8. Eddy, S., Mariani, L. H. & Kretzler, M. Integrated multi-omics approaches to improve classification of chronic kidney disease. Nat. Rev. Nephrol. 16, 657���668 (2020). [PMID: 32424281]
  9. El-Achkar, T. M. et al. Precision medicine in nephrology: an integrative framework of multidimensional data in the kidney precision medicine project. Am. J. Kidney Dis. 83, 402���410 (2024). [PMID: 37839688]
  10. El-Achkar, T. M. et al. A multimodal and integrated approach to interrogate human kidney biopsies with rigor and reproducibility: guidelines from the Kidney Precision Medicine Project. Physiol. Genom. 53, 1���11 (2020). [DOI: 10.1152/physiolgenomics.00104.2020]
  11. Snyder, M. P. et al. The human body at cellular resolution: the NIH Human Biomolecular Atlas Program. Nature 574, 187���192 (2019). [DOI: 10.1038/s41586-019-1629-x]
  12. Darshi, M., Van Espen, B. & Sharma, K. Metabolomics in diabetic kidney disease: unraveling the biochemistry of a silent killer. Am. J. Nephrol. 44, 92���103 (2016). [PMID: 27410520]
  13. Chen, C.-J., Lee, D.-Y., Yu, J., Lin, Y.-N. & Lin, T.-M. Recent advances in LC-MS-based metabolomics for clinical biomarker discovery. Mass Spectrom. Rev. 42, 2349���2378 (2023). [PMID: 35645144]
  14. Ahmed, S. et al. A robust, accurate, sensitive LC���MS/MS method to measure indoxyl sulfate, validated for plasma and kidney cells. Biomed. Chromatogr. 36, e5307 (2022). [PMID: 34978088]
  15. Lin, L. et al. Direct infusion mass spectrometry or liquid chromatography mass spectrometry for human metabonomics? A serum metabonomic study of kidney cancer. Analyst 135, 2970���2978 (2010). [PMID: 20856980]
  16. Zhao, Y.-Y., Vaziri, N. D. & Lin, R.-C. in Advances in Clinical Chemistry Vol. 68 (ed Makowski, G. S.) 153���175 (Elsevier, 2015).
  17. Dabija, L. G., Yousefi-Taemeh, M., Duli, E., Lemaire, M. & Ifa, D. R. Assessment of MALDI matrices for the detection and visualization of phosphatidylinositols and phosphoinositides in mouse kidneys through matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI). Anal. Bioanal. Chem. 416, 1857���1865 (2024). [PMID: 38319357]
  18. Sharma, K. et al. Endogenous adenine mediates kidney injury in diabetic models and predicts diabetic kidney disease in patients. J. Clin. Invest. 133, e170341 (2023). [PMID: 37616058]
  19. Asowata, E. O. et al. Multi-omics and imaging mass cytometry characterization of human kidneys to identify pathways and phenotypes associated with impaired kidney function. Kidney Int. 106, 85���97 (2024). [PMID: 38431215]
  20. Li, H. et al. Transcriptomic, epigenomic, and spatial metabolomic cell profiling redefines regional human kidney anatomy. Cell Metab. 36, 1105���1125.e10 (2024). [PMID: 38513647]
  21. Golf, O. et al. Rapid evaporative ionization mass spectrometry imaging platform for direct mapping from bulk tissue and bacterial growth media. Anal. Chem. 87, 2527���2534 (2015). [PMID: 25671656]
  22. Balog, J. et al. Intraoperative tissue identification using rapid evaporative ionization mass 5(194):194ra93spectrometry. Sci. Transl. Med. 5, 194ra93 (2013). [PMID: 23863833]
  23. Zhang, J. et al. Clinical translation and evaluation of a handheld and biocompatible mass spectrometry probe for surgical use. Clin. Chem. 67, 1271���1280 (2021). [PMID: 34263289]
  24. Garza, K. Y. et al. Rapid screening of COVID-19 directly from clinical nasopharyngeal swabs using the MasSpec pen. Anal. Chem. 93, 12582���12593 (2021). [PMID: 34432430]
  25. Harkin, C. et al. On-tissue chemical derivatization in mass spectrometry imaging. Mass Spectrom. Rev. 41, 662���694 (2022). [PMID: 33433028]
  26. Yagnik, G., Liu, Z., Rothschild, K. J. & Lim, M. J. Highly multiplexed immunohistochemical MALDI-MS imaging of biomarkers in tissues. J. Am. Soc. Mass. Spectrom. 32, 977���988 (2021). [PMID: 33631930]
  27. Bender, K. J. et al. Sample preparation method for MALDI mass spectrometry imaging of fresh-frozen spines. Anal. Chem. 95, 17337���17346 (2023). [PMID: 37886878]
  28. Xiao, Y. et al. Recent advances of ambient mass spectrometry imaging for biological tissues: a review. Anal. Chim. Acta 1117, 74���88 (2020). [PMID: 32408956]
  29. Taylor, M. J., Lukowski, J. K. & Anderton, C. R. Spatially resolved mass spectrometry at the single cell: recent innovations in proteomics and metabolomics. J. Am. Soc. Mass. Spectrom. 32, 872���894 (2021). [PMID: 33656885]
  30. Alexandrov, T. Spatial metabolomics and imaging mass spectrometry in the age of artificial intelligence. Annu. Rev. Biomed. Data Sci. 3, 61���87 (2020). [PMID: 34056560]
  31. Doble, P. A., de Vega, R. G., Bishop, D. P., Hare, D. J. & Clases, D. Laser ablation���inductively coupled plasma���mass spectrometry imaging in biology. Chem. Rev. 121, 11769���11822 (2021). [PMID: 34019411]
  32. Gorman, B. L. et al. Applying multimodal mass spectrometry to image tumors undergoing ferroptosis following in vivo treatment with a ferroptosis inducer. J. Am. Soc. Mass Spectrom. 35, 5���12 (2024). [PMID: 38079508]
  33. He, M. J. et al. Comparing DESI-MSI and MALDI-MSI mediated spatial metabolomics and their applications in cancer studies. Front. Oncol. 12, 891018 (2022). [PMID: 35924152]
  34. Noun, M., Akoumeh, R. & Abbas, I. Cell and tissue imaging by TOF-SIMS and MALDI-TOF: an overview for biological and pharmaceutical analysis. Microsc. Microanal. 28, 1���26 (2022). [PMID: 34809729]
  35. Palmer, A., Trede, D. & Alexandrov, T. Where imaging mass spectrometry stands: here are the numbers. Metabolomics 12, 107 (2016). [DOI: 10.1007/s11306-016-1047-0]
  36. Zeng, Q. et al. Recent developments in ionization techniques for single-cell mass spectrometry. Front. Chem. 11, 1293533 (2023). [PMID: 38130875]
  37. Chughtai, K. & Heeren, R. M. A. Mass spectrometric imaging for biomedical tissue analysis. Chem. Rev. 110, 3237���3277 (2010). [PMID: 20423155]
  38. Stopka, S. A. et al. Ambient metabolic profiling and imaging of biological samples with ultrahigh molecular resolution using laser ablation electrospray ionization 21 Tesla FTICR mass spectrometry. Anal. Chem. 91, 5028���5035 (2019). [PMID: 30821434]
  39. Wang, M. F. et al. Lipidomic analysis of mouse brain to evaluate the efficacy and preservation of different tissue preparatory techniques by IR-MALDESI-MSI. J. Am. Soc. Mass Spectrom. 34, 869���877 (2023). [PMID: 36988291]
  40. M��ller, W. H., De Pauw, E., Far, J., Malherbe, C. & Eppe, G. Imaging lipids in biological samples with surface-assisted laser desorption/ionization mass spectrometry: a concise review of the last decade. Prog. Lipid Res. 83, 101114 (2021). [PMID: 34217733]
  41. Nu��ez, J., Renslow, R., Cliff, J. B. III & Anderton, C. R. NanoSIMS for biological applications: current practices and analyses. Biointerphases 13, 03B301 (2017). [PMID: 28954518]
  42. Harper, J. D. et al. Low-temperature plasma probe for ambient desorption ionization. Anal. Chem. 80, 9097���9104 (2008). [PMID: 19551980]
  43. Mart��nez-Jarqu��n, S. & Winkler, R. Low-temperature plasma (LTP) jets for mass spectrometry (MS): ion processes, instrumental set-ups, and application examples. Trends Analyt. Chem. 89, 133���145 (2017). [DOI: 10.1016/j.trac.2017.01.013]
  44. Mart��nez-Jarqu��n, S., Herrera-Ubaldo, H., de Folter, S. & Winkler, R. In vivo monitoring of nicotine biosynthesis in tobacco leaves by low-temperature plasma mass spectrometry. Talanta 185, 324���327 (2018). [PMID: 29759207]
  45. Ma, S. et al. High spatial resolution mass spectrometry imaging for spatial metabolomics: advances, challenges, and future perspectives. Trends Analyt. Chem. 159, 116902 (2023). [DOI: 10.1016/j.trac.2022.116902]
  46. Shariatgorji, M. et al. Direct imaging of elemental distributions in tissue sections by laser ablation mass spectrometry. Methods 104, 86���92 (2016). [PMID: 27263025]
  47. Van Acker, T. et al. High-resolution laser ablation-inductively coupled plasma-mass spectrometry imaging of cisplatin-induced nephrotoxic side effects. Anal. Chim. Acta 945, 23���30 (2016). [PMID: 27968712]
  48. Unsihuay, D. et al. High-resolution imaging and identification of biomolecules using Nano-DESI coupled to ion mobility spectrometry. Anal. Chim. Acta 1186, 339085 (2021). [PMID: 34756271]
  49. Kumar, B. S. Desorption electrospray ionization mass spectrometry imaging (DESI-MSI) in disease diagnosis: an overview. Anal. Methods 15, 3768���3784 (2023). [PMID: 37503728]
  50. Laskin, J., Heath, B. S., Roach, P. J., Cazares, L. & Semmes, O. J. Tissue imaging using nanospray desorption electrospray ionization mass spectrometry. Anal. Chem. 84, 141���148 (2012). [PMID: 22098105]
  51. Hendriks, T. F. E. et al. MALDI-MSI-LC-MS/MS workflow for single-section single step combined proteomics and quantitative lipidomics. Anal. Chem. 96, 4266���4274 (2024). [PMID: 38469638]
  52. Piehowski, P. D. et al. Automated mass spectrometry imaging of over 2000 proteins from tissue sections at 100-��m spatial resolution. Nat. Commun. 11, 8 (2020). [PMID: 31911630]
  53. Zhu, Y. et al. Spatially resolved proteome mapping of laser capture microdissected tissue with automated sample transfer to nanodroplets. Mol. Cell. Proteomics 17, 1864���1874 (2018). [PMID: 29941660]
  54. Sigdel, T. K. et al. Near-single-cell proteomics profiling of the proximal tubular and glomerulus of the normal human kidney. Front. Med. 7, 499 (2020). [DOI: 10.3389/fmed.2020.00499]
  55. Hansen, J. et al. A reference tissue atlas for the human kidney. Sci. Adv. 8, eabn4965 (2022). [PMID: 35675394]
  56. Lukowski, J. K. et al. Storage conditions of human kidney tissue sections affect spatial lipidomics analysis reproducibility. J. Am. Soc. Mass Spectrom. 31, 2538���2546 (2020). [PMID: 32897710]
  57. Walch, A., Rauser, S., Deininger, S.-O. & H��fler, H. MALDI imaging mass spectrometry for direct tissue analysis: a new frontier for molecular histology. Histochem. Cell Biol. 130, 421���434 (2008). [PMID: 18618129]
  58. Tasca, P. et al. Application of spatial-omics to the classification of kidney biopsy samples in transplantation. Nat. Rev. Nephrol. 20, 755���766 (2024). [PMID: 38965417]
  59. Nwosu, A. J. et al. In-depth mass spectrometry-based proteomics of formalin-fixed, paraffin-embedded tissues with a spatial resolution of 50���200 ��m. J. Proteome Res. 21, 2237���2245 (2022). [PMID: 35916235]
  60. Powers, T. W. et al. MALDI imaging mass spectrometry profiling of N-glycans in formalin-fixed paraffin embedded clinical tissue blocks and tissue microarrays. PLoS ONE 9, e106255 (2014). [PMID: 25184632]
  61. Ferri-Borgogno, S. et al. Molecular, metabolic, and subcellular mapping of the tumor immune microenvironment via 3D targeted and non-targeted multiplex multi-omics analyses. Cancers 16, 846 (2024). [PMID: 38473208]
  62. Patterson, N. H., Tuck, M., Van de Plas, R. & Caprioli, R. M. Advanced registration and analysis of MALDI imaging mass spectrometry measurements through autofluorescence microscopy. Anal. Chem. 90, 12395���12403 (2018). [PMID: 30272960]
  63. Fiehn, O. et al. The metabolomics standards initiative (MSI). Metabolomics 3, 175���178 (2007). [DOI: 10.1007/s11306-007-0070-6]
  64. Gonz��lez-Dom��nguez, R., Gonz��lez-Dom��nguez, ��., Sayago, A. & Fern��ndez-Recamales, ��. Recommendations and best practices for standardizing the pre-analytical processing of blood and urine samples in metabolomics. Metabolites 10, 229 (2020). [PMID: 32503183]
  65. Smith, L. et al. Important considerations for sample collection in metabolomics studies with a special focus on applications to liver functions. Metabolites 10, 104 (2020). [PMID: 32178364]
  66. Yin, P., Lehmann, R. & Xu, G. Effects of pre-analytical processes on blood samples used in metabolomics studies. Anal. Bioanal. Chem. 407, 4879���4892 (2015). [PMID: 25736245]
  67. Hoyer, K. J. R., Dittrich, S., Bartram, M. P. & Rinschen, M. M. Quantification of molecular heterogeneity in kidney tissue by targeted proteomics. J. Proteomics 193, 85���92 (2019). [PMID: 29522878]
  68. Varnavides, G. et al. In search of a universal method: a comparative survey of bottom-up proteomics sample preparation methods. J. Proteome Res. 21, 2397���2411 (2022). [PMID: 36006919]
  69. Vuckovic, D. in Proteomic and Metabolomic Approaches to Biomarker Discovery (eds Issaq, H. J. & Veenstra, T. D.) 51���75 (Academic Press, 2013).
  70. Bligh, E. G. & Dyer, W. J. A rapid method of total lipid extraction and purification. Can. J. Biochem. Physiol. 37, 911���917 (1959). [PMID: 13671378]
  71. Matyash, V., Liebisch, G., Kurzchalia, T. V., Shevchenko, A. & Schwudke, D. Lipid extraction by methyl-tert-butyl ether for high-throughput lipidomics. J. Lipid Res. 49, 1137���1146 (2008). [PMID: 18281723]
  72. L��fgren, L. et al. The BUME method: a novel automated chloroform-free 96-well total lipid extraction method for blood plasma. J. Lipid Res. 53, 1690���1700 (2012). [PMID: 22645248]
  73. Cui, M., Cheng, C. & Zhang, L. High-throughput proteomics: a methodological mini-review. Lab. Invest. 102, 1170���1181 (2022). [PMID: 35922478]
  74. Lukowski, J. K. et al. An optimized approach and inflation media for obtaining complimentary mass spectrometry-based omics data from human lung tissue. Front. Mol. Biosci. 9, 1022775 (2022). [PMID: 36465564]
  75. Nicora, C. D. et al. in MERS Coronavirus: Methods and Protocols (ed Vijay, R.) 173���194 (Springer, 2020).
  76. Halket, J. M. et al. Chemical derivatization and mass spectral libraries in metabolic profiling by GC/MS and LC/MS/MS. J. Exp. Bot. 56, 219���243 (2005). [PMID: 15618298]
  77. Su, P. et al. Highly multiplexed, label-free proteoform imaging of tissues by individual ion mass spectrometry. Sci. Adv. 8, eabp9929 (2022). [PMID: 35947651]
  78. Schlosser, P., Grams, M. E. & Rhee, E. P. Proteomics: progress and promise of high-throughput proteomics in chronic kidney disease. Mol. Cell. Proteomics 22, 100550 (2023). [PMID: 37076045]
  79. Li, X. et al. A simple, rapid and sensitive HILIC LC-MS/MS method for simultaneous determination of 16 purine metabolites in plasma and urine. Talanta 267, 125171 (2024). [PMID: 37696233]
  80. Wen, D. et al. Metabolite profiling of CKD progression in the chronic renal insufficiency cohort study. JCI Insight 7, e161696 (2022). [PMID: 36048534]
  81. Sharma, K. et al. Metabolomics reveals signature of mitochondrial dysfunction in diabetic kidney disease. J. Am. Soc. Nephrol. 24, 1901���1912 (2013). [PMID: 23949796]
  82. Azushima, K. et al. Abnormal lactate metabolism is linked to albuminuria and kidney injury in diabetic nephropathy. Kidney Int. 104, 1135���1149 (2023). [PMID: 37843477]
  83. Ragi, N. et al. Assessment of uremic toxins in advanced chronic kidney disease patients on maintenance hemodialysis by LC-ESI-MS/MS. Metabolomics 19, 14 (2023). [PMID: 36826619]
  84. Ragi, N. et al. Screening DNA damage in the rat kidney and liver by untargeted DNA adductomics. Chem. Res. Toxicol. 37, 340���360 (2024). [PMID: 38194517]
  85. Joshi, N., Garapati, K., Ghose, V., Kandasamy, R. K. & Pandey, A. Recent progress in mass spectrometry-based urinary proteomics. Clin. Proteom. 21, 14 (2024). [DOI: 10.1186/s12014-024-09462-z]
  86. Ram��rez Medina, C. R. et al. Proteomic signature associated with chronic kidney disease (CKD) progression identified by data-independent acquisition mass spectrometry. Clin. Proteom. 20, 19 (2023). [DOI: 10.1186/s12014-023-09405-0]
  87. Nimer, R. M., Alfaqih, M. A., Shehabat, E. R., Mujammami, M. & Abdel Rahman, A. M. Label-free quantitative proteomics analysis for type 2 diabetes mellitus early diagnostic marker discovery using data-independent acquisition mass spectrometry (DIA-MS). Sci. Rep. 13, 20880 (2023). [PMID: 38012280]
  88. Rinschen, M. M. & Saez-Rodriguez, J. The tissue proteome in the multi-omic landscape of kidney disease. Nat. Rev. Nephrol. 17, 205���219 (2021). [PMID: 33028957]
  89. Reilly, D. F. & Breyer, M. D. The use of genomics to drive kidney disease drug discovery and development. Clin. J. Am. Soc. Nephrol. 15, 1342���1351 (2020). [PMID: 32193173]
  90. Lin, W. et al. Integrated metabolomics and proteomics reveal biomarkers associated with hemodialysis in end-stage kidney disease. Front. Pharmacol. 14, 1243505 (2023). [PMID: 38089059]
  91. Wilmes, A. et al. Application of integrated transcriptomic, proteomic and metabolomic profiling for the delineation of mechanisms of drug induced cell stress. J. Proteom. 79, 180���194 (2013). [DOI: 10.1016/j.jprot.2012.11.022]
  92. Debeljak, ��. et al. MALDI TOF mass spectrometry imaging of blood smear: method development and evaluation. Int. J. Mol. Sci. 22, 585 (2021). [PMID: 33430160]
  93. Wang, Z. et al. Spatial-resolved metabolomics reveals tissue-specific metabolic reprogramming in diabetic nephropathy by using mass spectrometry imaging. Acta Pharm. Sin. B 11, 3665���3677 (2021). [PMID: 34900545]
  94. Unsihuay, D., Mesa Sanchez, D. & Laskin, J. Quantitative mass spectrometry imaging of biological systems. Annu. Rev. Phys. Chem. 72, 307���329 (2021). [PMID: 33441032]
  95. Chumbley, C. W. et al. Absolute quantitative MALDI imaging mass spectrometry: a case of rifampicin in liver tissues. Anal. Chem. 88, 2392���2398 (2016). [PMID: 26814665]
  96. Holbrook, J. H., Kemper, G. E. & Hummon, A. B. Quantitative mass spectrometry imaging: therapeutics & biomolecules. Chem. Commun. 60, 2137���2151 (2024). [DOI: 10.1039/D3CC05988J]
  97. Mesa Sanchez, D. et al. Mass spectrometry imaging of diclofenac and its metabolites in tissues using nanospray desorption electrospray ionization. Anal. Chim. Acta 1233, 340490 (2022). [PMID: 36283780]
  98. Liebisch, G. et al. Update on LIPID MAPS classification, nomenclature, and shorthand notation for MS-derived lipid structures. J. Lipid Res. 61, 1539���1555 (2020). [PMID: 33037133]
  99. Cockcroft, S. Mammalian lipids: structure, synthesis and function. Essays Biochem. 65, 813���845 (2021). [PMID: 34415021]
  100. Levental, I. & Lyman, E. Regulation of membrane protein structure and function by their lipid nano-environment. Nat. Rev. Mol. Cell Biol. 24, 107���122 (2023). [PMID: 36056103]
  101. Yan, J. & Horng, T. Lipid metabolism in regulation of macrophage functions. Trends Cell Biol. 30, 979���989 (2020). [PMID: 33036870]
  102. Oshima, M. et al. Trajectories of kidney function in diabetes: a clinicopathological update. Nat. Rev. Nephrology 17, 740���750 (2021). [PMID: 34363037]
  103. Butt, L. et al. A molecular mechanism explaining albuminuria in kidney disease. Nat. Metab. 2, 461���474 (2020). [PMID: 32694662]
  104. Cannata-And��a, J. B. et al. Chronic kidney disease ��� mineral and bone disorders: pathogenesis and management. Calcif. Tissue Int. 108, 410���422 (2021). [PMID: 33190187]
  105. Vallon, V. & Thomson, S. C. The tubular hypothesis of nephron filtration and diabetic kidney disease. Nat. Rev. Nephrol. 16, 317���336 (2020). [PMID: 32152499]
  106. Harkin, C. et al. Spatial localization of ��-unsaturated aldehyde markers in murine diabetic kidney tissue by mass spectrometry imaging. Anal. Bioanal. Chem. 414, 6657���6670 (2022). [PMID: 35881173]
  107. Wang, G. et al. Analyzing cell-type-specific dynamics of metabolism in kidney repair. Nat. Metab. 4, 1109���1118 (2022). [PMID: 36008550]
  108. Mart��n-Saiz, L. et al. Using the synergy between HPLC-MS and MALDI-MS imaging to explore the lipidomics of clear cell renal cell carcinoma. Anal. Chem. 95, 2285���2293 (2023). [PMID: 36638042]
  109. Erlmeier, F. et al. Matrix-assisted laser desorption/ionization mass spectrometry imaging: diagnostic pathways and metabolites for renal tumor entities. Oncology 101, 126���133 (2023). [PMID: 36198279]
  110. Rietjens, R. G. J. et al. Phosphatidylinositol metabolism of the renal proximal tubule S3 segment is disturbed in response to diabetes. Sci. Rep. 13, 6261 (2023). [PMID: 37069341]
  111. Mondal, S. et al. Rapid molecular evaluation of human kidney tissue sections by in situ mass spectrometry and machine learning to classify the nephrotic syndrome. J. Proteome Res. 22, 967���976 (2023). [PMID: 36696358]
  112. Zhang, X. et al. Comparison of local metabolic changes in diabetic rodent kidneys using mass spectrometry imaging. Metabolites 13, 324 (2023). [PMID: 36984764]
  113. Heuckeroth, S. et al. On-tissue dataset-dependent MALDI-TIMS-MS2 bioimaging. Nat. Commun. 14, 7495 (2023). [PMID: 37980348]
  114. Neumann, E. K. et al. Spatial metabolomics of the human kidney using MALDI trapped ion mobility imaging mass spectrometry. Anal. Chem. 92, 13084���13091 (2020). [PMID: 32668145]
  115. van Veelen, P. A. et al. Direct peptide profiling of single neurons by matrix-assisted laser desorption���ionization mass spectrometry. Org. Mass Spectrom. 28, 1542���1546 (1993). [DOI: 10.1002/oms.1210281229]
  116. Spraggins, J. M. et al. Next-generation technologies for spatial proteomics: integrating ultra-high speed MALDI-TOF and high mass resolution MALDI FTICR imaging mass spectrometry for protein analysis. Proteomics 16, 1678���1689 (2016). [PMID: 27060368]
  117. Zemaitis, K. J. et al. Enhanced spatial mapping of histone proteoforms in human kidney through MALDI-MSI by high-field UHMR-Orbitrap detection. Anal. Chem. 94, 12604���12613 (2022). [PMID: 36067026]
  118. Hale, O. J. & Cooper, H. J. Native mass spectrometry imaging of proteins and protein complexes by nano-DESI. Anal. Chem. 93, 4619���4627 (2021). [PMID: 33661614]
  119. Hale, O. J., Sisley, E. K., Griffiths, R. L., Styles, I. B. & Cooper, H. J. Native LESA TWIMS-MSI: spatial, conformational, and mass analysis of proteins and protein complexes. J. Am. Soc. Mass Spectrom. 31, 873���879 (2020). [PMID: 32159346]
  120. Javanshad, R., Honarvar, E. & Venter, A. R. Addition of serine enhances protein analysis by DESI-MS. J. Am. Soc. Mass Spectrom. 30, 694���703 (2019). [PMID: 30771107]
  121. Yang, M. et al. Proteoform-selective imaging of tissues using mass spectrometry. Angew. Chem. Int. Ed. 61, (2022).
  122. Yang, M. et al. Nano-DESI mass spectrometry imaging of proteoforms in biological tissues with high spatial resolution. Anal. Chem. 95, 5214���5222 (2023). [PMID: 36917636]
  123. Kiss, A., Smith, D. F., Reschke, B. R., Powell, M. J. & Heeren, R. M. A. Top-down mass spectrometry imaging of intact proteins by laser ablation ESI FT-ICR MS. Proteomics 14, 1283���1289 (2014). [PMID: 24375984]
  124. Kooijman, P. C., Mathew, A., Ellis, S. R. & Heeren, R. M. A. Infrared laser desorption and electrospray ionisation of non-covalent protein complexes: generation of intact, multiply charged species. Anal. Sens. 1, 44���47 (2021).
  125. Pu, F. et al. High-throughput intact protein analysis for drug discovery using infrared matrix-assisted laser desorption electrospray ionization mass spectrometry. Anal. Chem. 94, 13566���13574 (2022). [PMID: 36129783]
  126. Williams, S. M. et al. Automated coupling of nanodroplet sample preparation with liquid chromatography���mass spectrometry for high-throughput single-cell proteomics. Anal. Chem. 92, 10588���10596 (2020). [PMID: 32639140]
  127. Li, Z.-Y. et al. Nanoliter-scale oil-air-droplet chip-based single cell proteomic analysis. Anal. Chem. 90, 5430���5438 (2018). [PMID: 29551058]
  128. Park, M., Casini, A. & Strittmatter, N. Seeing the invisible: preparative strategies to visualise elusive molecules using mass spectrometry imaging. Trends Anal. Chem. 168, 117304 (2023). [DOI: 10.1016/j.trac.2023.117304]
  129. Giesen, C. et al. Highly multiplexed imaging of tumor tissues with subcellular resolution by mass cytometry. Nat. Methods 11, 417���422 (2014). [PMID: 24584193]
  130. Keren, L. et al. MIBI-TOF: a multiplexed imaging platform relates cellular phenotypes and tissue structure. Sci. Adv. 5, eaax5851 (2019). [PMID: 31633026]
  131. Damond, N. et al. A map of human type 1 diabetes progression by imaging mass cytometry. Cell Metab. 29, 755���768.e5 (2019). [PMID: 30713109]
  132. Baxter, R. M. et al. Expansion of extrafollicular B and T cell subsets in childhood-onset systemic lupus erythematosus. Front. Immunol. 14, 1208282 (2023). [PMID: 37965329]
  133. Duivenvoorden, A. A. M. et al. Lipidomic phenotyping of human small intestinal organoids using matrix-assisted laser desorption/ionization mass spectrometry imaging. Anal. Chem. 95, 18443���18450 (2023). [PMID: 38060464]
  134. Lim, M. J. et al. MALDI HiPLEX-IHC: multiomic and multimodal imaging of targeted intact proteins in tissues. Front. Chem. 11, 1182404 (2023). [PMID: 37201132]
  135. Dunne, J. et al. Evaluation of antibody-based single cell type imaging techniques coupled to multiplexed imaging of N-glycans and collagen peptides by matrix-assisted laser desorption/ionization mass spectrometry imaging. Anal. Bioanal. Chem. 415, 7011���7024 (2023). [PMID: 37843548]
  136. Young, L. E. A. et al. Utilizing multimodal mass spectrometry imaging for profiling immune cell composition and N-glycosylation across colorectal carcinoma disease progression. Front. Pharmacol. 14, 1337319 (2024). [PMID: 38273829]
  137. Groseclose, M. R., Andersson, M., Hardesty, W. M. & Caprioli, R. M. Identification of proteins directly from tissue: in situ tryptic digestions coupled with imaging mass spectrometry. J. Mass Spectrom. 42, 254���262 (2007). [PMID: 17230433]
  138. Cillero-Pastor, B. & Heeren, R. M. A. Matrix-assisted laser desorption ionization mass spectrometry imaging for peptide and protein analyses: a critical review of on-tissue digestion. J. Proteome Res. 13, 325���335 (2014). [PMID: 24087847]
  139. Angel, P. M. et al. Mapping extracellular matrix proteins in formalin-fixed, paraffin-embedded tissues by MALDI imaging mass spectrometry. J. Proteome Res. 17, 635���646 (2018). [PMID: 29161047]
  140. Clift, C. L., Drake, R. R., Mehta, A. & Angel, P. M. Multiplexed imaging mass spectrometry of the extracellular matrix using serial enzyme digests from formalin-fixed paraffin-embedded tissue sections. Anal. Bioanal. Chem. 413, 2709���2719 (2021). [PMID: 33206215]
  141. Enthaler, B. et al. MALDI imaging in human skin tissue sections: focus on various matrices and enzymes. Anal. Bioanal. Chem. 405, 1159���1170 (2013). [PMID: 23138471]
  142. Drake, R. R., West, C. A., Mehta, A. S. & Angel, P. M. in Glycobiophysics (eds Yamaguchi, Y. & Kato, K.) 59���76 (Springer, 2018).
  143. Wallace, E. N. et al. An N-glycome tissue atlas of 15 human normal and cancer tissue types determined by MALDI-imaging mass spectrometry. Sci. Rep. 14, 489 (2024). [PMID: 38177192]
  144. B��low, R. D. & Boor, P. Extracellular matrix in kidney fibrosis: more than just a scaffold. J. Histochem. Cytochem. 67, 643���661 (2019). [PMID: 31116062]
  145. Naba, A. Ten years of extracellular matrix proteomics: accomplishments, challenges, and future perspectives. Mol. Cell. Proteomics 22, 100528 (2023). [PMID: 36918099]
  146. Angel, P. M. et al. Extracellular matrix alterations in low-grade lung adenocarcinoma compared with normal lung tissue by imaging mass spectrometry. J. Mass Spectrom. 55, e4450 (2020). [PMID: 31654589]
  147. Lennon, R. et al. Global analysis reveals the complexity of the human glomerular extracellular matrix. J. Am. Soc. Nephrol. 25, 939���951 (2014). [PMID: 24436468]
  148. Varki, A. Biological roles of glycans. Glycobiology 27, 3���49 (2017). [PMID: 27558841]
  149. Bermingham, M. L. et al. N-glycan profile and kidney disease in type 1 diabetes. Diabetes Care 41, 79���87 (2017). [PMID: 29146600]
  150. Shayman, J. A. Targeting glycosphingolipid metabolism to treat kidney disease. Nephron 134, 37���42 (2016). [PMID: 26954668]
  151. Natoli, T. A., Modur, V. & Ibraghimov-Beskrovnaya, O. Glycosphingolipid metabolism and polycystic kidney disease. Cell. Signal. 69, 109526 (2020). [PMID: 31911181]
  152. Drake, R. R. et al. Defining the human kidney N-glycome in normal and cancer tissues using MALDI imaging mass spectrometry. J. Mass Spectrom. 55, e4490 (2020). [PMID: 31860772]
  153. Veli��kovi��, D. et al. Rapid automated annotation and analysis of N-glycan mass spectrometry imaging data sets using NGlycDB in METASPACE. Anal. Chem. 93, 13421���13425 (2021). [PMID: 34581565]
  154. Veli��kovi��, D., Sharma, K., Alexandrov, T., Hodgin, J. B. & Anderton, C. R. Controlled humidity levels for fine spatial detail information in enzyme-assisted N-glycan MALDI MSI. J. Am. Soc. Mass Spectrom. 33, 1577���1580 (2022). [PMID: 35802124]
  155. Piras, D. et al. Kidney size in relation to ageing, gender, renal function, birthweight and chronic kidney disease risk factors in a general population. Nephrol. Dial. Transplant. 35, 640���647 (2020). [PMID: 30169833]
  156. Neumann, E. K. et al. Highly multiplexed immunofluorescence of the human kidney using co-detection by indexing. Kidney Int. 101, 137���143 (2022). [PMID: 34619231]
  157. Haug, S. et al. Multi-omic analysis of human kidney tissue identified medulla-specific gene expression patterns. Kidney Int. 105, 293���311 (2024). [PMID: 37995909]
  158. Bowman, A. P. et al. Evaluation of lipid coverage and high spatial resolution MALDI-imaging capabilities of oversampling combined with laser post-ionisation. Anal. Bioanal. Chem. 412, 2277���2289 (2020). [PMID: 31879798]
  159. Niehaus, M., Soltwisch, J., Belov, M. E. & Dreisewerd, K. Transmission-mode MALDI-2 mass spectrometry imaging of cells and tissues at subcellular resolution. Nat. Methods 16, 925���931 (2019). [PMID: 31451764]
  160. Bien, T., Bessler, S., Dreisewerd, K. & Soltwisch, J. Transmission-mode MALDI mass spectrometry imaging of single cells: optimizing sample preparation protocols. Anal. Chem. 93, 4513���4520 (2021). [PMID: 33646746]
  161. Soltwisch, J. et al. MALDI-2 on a trapped ion mobility quadrupole time-of-flight instrument for rapid mass spectrometry imaging and ion mobility separation of complex lipid profiles. Anal. Chem. 92, 8697���8703 (2020). [PMID: 32449347]
  162. Fu, T. et al. In situ isobaric lipid mapping by MALDI���ion mobility separation���mass spectrometry imaging. J. Mass Spectrom. 55, e4531 (2020). [PMID: 32567158]
  163. Tokunaga, E., Yamamoto, T., Ito, E. & Shibata, N. Understanding the thalidomide chirality in biological processes by the self-disproportionation of enantiomers. Sci. Rep. 8, 17131 (2018). [PMID: 30459439]
  164. Rivera, E. S., Djambazova, K. V., Neumann, E. K., Caprioli, R. M. & Spraggins, J. M. Integrating ion mobility and imaging mass spectrometry for comprehensive analysis of biological tissues: a brief review and perspective. J. Mass Spectrom. 55, e4614 (2020). [PMID: 32955134]
  165. Causon, T. J., Kurulugama, R. T. & Hann, S. in Ion Mobility-Mass Spectrometry : Methods and Protocols (eds Paglia, G. & Astarita, G.) 79���94 (Springer, 2020).
  166. Hale, O. J., Hughes, J. W. & Cooper, H. J. Simultaneous spatial, conformational, and mass analysis of intact proteins and protein assemblies by nano-DESI travelling wave ion mobility mass spectrometry imaging. Int. J. Mass Spectrom. 468, 116656 (2021). [DOI: 10.1016/j.ijms.2021.116656]
  167. Chacon, A. et al. On-tissue chemical derivatization of 3-methoxysalicylamine for MALDI-imaging mass spectrometry. J. Mass Spectrom. 46, 840���846 (2011). [PMID: 21834023]
  168. Merdas, M. et al. On-tissue chemical derivatization reagents for matrix-assisted laser desorption/ionization mass spectrometry imaging. J. Mass Spectrom. 56, e4731 (2021). [PMID: 34080257]
  169. Zemaitis, K. J. et al. Expanded coverage of phytocompounds by mass spectrometry imaging using on-tissue chemical derivatization by 4-APEBA. Anal. Chem. 95, 12701���12709 (2023). [PMID: 37594382]
  170. Smith, K. W. et al. Spatial localization of vitamin D metabolites in mouse kidney by mass spectrometry imaging. ACS Omega 5, 13430���13437 (2020). [PMID: 32548531]
  171. Sun, C., Liu, W., Geng, Y. & Wang, X. On-tissue derivatization strategy for mass spectrometry imaging of carboxyl-containing metabolites in biological tissues. Anal. Chem. 92, 12126���12131 (2020). [PMID: 32786442]
  172. Wang, L. et al. On-tissue chemical oxidation followed by derivatization for mass spectrometry imaging enables visualization of primary and secondary hydroxyl-containing metabolites in biological tissues. Anal. Chem. 95, 1975���1984 (2023). [DOI: 10.1021/acs.analchem.2c04316]
  173. Zang, Q. et al. Enhanced on-tissue chemical derivatization with hydrogel assistance for mass spectrometry imaging. Anal. Chem. 93, 15373���15380 (2021). [PMID: 34748327]
  174. Esselman, A. B. et al. In situ molecular profiles of glomerular cells by integrated imaging mass spectrometry and multiplexed immunofluorescence microscopy. Kidney Int. 107, 332���337 (2024). [PMID: 39571907]
  175. Neumann, E. K., Djambazova, K. V., Caprioli, R. M. & Spraggins, J. M. Multimodal imaging mass spectrometry: next generation molecular mapping in biology and medicine. J. Am. Soc. Mass Spectrom. 31, 2401���2415 (2020). [PMID: 32886506]
  176. Neumann, E. K. et al. Protocol for multimodal analysis of human kidney tissue by imaging mass spectrometry and CODEX multiplexed immunofluorescence. STAR Protoc. 2, 100747 (2021). [PMID: 34430920]
  177. Claes, B. S. R. et al. MALDI-IHC-guided in-depth spatial proteomics: targeted and untargeted MSI combined. Anal. Chem. 95, 2329���2338 (2023). [PMID: 36638208]
  178. Shafer, C. C. & Neumann, E. K. Optimized combination of MALDI MSI and immunofluorescence for neuroimaging of lipids within cellular microenvironments. Front. Chem. 12, 1334209 (2024). [PMID: 38406559]
  179. Lork, A. A., Vo, K. L. L. & Phan, N. T. N. Chemical imaging and analysis of single nerve cells by secondary ion mass spectrometry imaging and cellular electrochemistry. Front. Synaptic Neurosci. 14, 854957 (2022). [PMID: 35651734]
  180. Tuck, M. et al. Multimodal imaging based on vibrational spectroscopies and mass spectrometry imaging applied to biological tissue: a multiscale and multiomics review. Anal. Chem. 93, 445���477 (2021). [PMID: 33253546]
  181. Marx, V. Method of the Year: spatially resolved transcriptomics. Nat. Methods 18, 9���14 (2021). [PMID: 33408395]
  182. Moses, L. & Pachter, L. Museum of spatial transcriptomics. Nat. Methods 19, 534���546 (2022). [PMID: 35273392]
  183. Yang, E. et al. RaMALDI: enabling simultaneous Raman and MALDI imaging of the same tissue section. Biosens. Bioelectron. 239, 115597 (2023). [PMID: 37597501]
  184. Esselman, A. B. et al. Microscopy-directed imaging mass spectrometry for rapid high spatial resolution molecular imaging of glomeruli. J. Am. Soc. Mass Spectrom. 34, 1305���1314 (2023). [PMID: 37319264]
  185. Alexandrov, T. MALDI imaging mass spectrometry: statistical data analysis and current computational challenges. BMC Bioinforma. 13, S11 (2012). [DOI: 10.1186/1471-2105-13-S16-S11]
  186. Nguyen, D. D. et al. Facilitating imaging mass spectrometry of microbial specialized metabolites with METASPACE. Metabolites 11, 477 (2021). [PMID: 34436418]
  187. Eisenberg, S. M., Knizner, K. T. & Muddiman, D. C. Metabolite Annotation Confidence Score (MACS): a novel MSI identification scoring tool. J. Am. Soc. Mass Spectrom. 34, 2222���2231 (2023). [PMID: 37606933]
  188. Bemis, K. A., F��ll, M. C., Guo, D., Lakkimsetty, S. S. & Vitek, O. Cardinal v.3: a versatile open-source software for mass spectrometry imaging analysis. Nat. Methods 20, 1883���1886 (2023). [PMID: 37996752]
  189. Patterson, N. H. et al. Next generation histology-directed imaging mass spectrometry driven by autofluorescence microscopy. Anal. Chem. 90, 12404���12413 (2018). [PMID: 30274514]
  190. Tarolli, J. G., Jackson, L. M. & Winograd, N. Improving secondary ion mass spectrometry image quality with image fusion. J. Am. Soc. Mass Spectrom. 25, 2154���2162 (2014). [PMID: 24912432]
  191. Galli, M., Zoppis, I., Smith, A., Magni, F. & Mauri, G. Machine learning approaches in MALDI-MSI: clinical applications. Expert Rev. Proteom. 13, 685���696 (2016). [DOI: 10.1080/14789450.2016.1200470]
  192. Verbeeck, N., Caprioli, R. M. & Van de Plas, R. Unsupervised machine learning for exploratory data analysis in imaging mass spectrometry. Mass Spectrom. Rev. 39, 245���291 (2020). [PMID: 31602691]
  193. Enzlein, T. et al. Computational analysis of Alzheimer amyloid plaque composition in 2D- and elastically reconstructed 3D-MALDI MS images. Anal. Chem. 92, 14484���14493 (2020). [PMID: 33138378]
  194. Cao, J. et al. Mass spectrometry imaging of L-[ring-C]-labeled phenylalanine and tyrosine kinetics in non-small cell lung carcinoma.Cancer Metab. 9, 26 (2021). [PMID: 34116702]
  195. Gorman, B. L. & Kraft, M. L. High-resolution secondary ion mass spectrometry analysis of cell membranes. Anal. Chem. 92, 1645���1652 (2020). [PMID: 31854976]
  196. Ovchinnikova, K., Kovalev, V., Stuart, L. & Alexandrov, T. OffsampleAI: artificial intelligence approach to recognize off-sample mass spectrometry images. BMC Bioinformatics 21, 129 (2020). [PMID: 32245392]
  197. Wadie, B. et al. METASPACE-ML: context-specific metabolite annotation for imaging mass spectrometry using machine learning. Nat. Commun. 15, 9110 (2024). [PMID: 39438443]
  198. Palmer, A. et al. FDR-controlled metabolite annotation for high-resolution imaging mass spectrometry. Nat. Methods 14, 57���60 (2017). [PMID: 27842059]
  199. Zhang, H. et al. Recent advances in mass spectrometry imaging combined with artificial intelligence for spatially clarifying molecular profiles: toward biomedical applications. Trends Anal. Chem. 178, 117834 (2024). [DOI: 10.1016/j.trac.2024.117834]

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