Data-Driven and Machine Learning-Based Framework for Image-Guided Single-Cell Mass Spectrometry

Overview

Journal J Proteome Res

Publisher American Chemical Society

Specialty Biochemistry

Date 2023 Jan 25

PMID 36695570

Authors

Yuxuan Richard Xie

Varsha K Chari

Daniel C Castro

Romans Grant

Stanislav S Rubakhin

Jonathan V Sweedler

Affiliations

Soon will be listed here.

Abstract

Improved throughput of analysis and lowered limits of detection have allowed single-cell chemical analysis to go beyond the detection of a few molecules in such volume-limited samples, enabling researchers to characterize different functional states of individual cells. Image-guided single-cell mass spectrometry leverages optical and fluorescence microscopy in the high-throughput analysis of cellular and subcellular targets. In this work, we propose DATSIGMA (ta-driven ools for ingle-cell analysis using mage-uided ss spectrometry), a workflow based on data-driven and machine learning approaches for feature extraction and enhanced interpretability of complex single-cell mass spectrometry data. Here, we implemented our toolset with user-friendly programs and tested it on multiple experimental data sets that cover a wide range of biological applications, including classifying various brain cell types. Because it is open-source, it offers a high level of customization and can be easily adapted to other types of single-cell mass spectrometry data.

Citing Articles

Mass-Guided Single-Cell MALDI Imaging of Low-Mass Metabolites Reveals Cellular Activation Markers.

Cairns J, Huber J, Lewen A, Jung J, Maurer S, Bausbacher T Adv Sci (Weinh). 2024; 12(5):e2410506.

PMID: 39665230 PMC: 11791930. DOI: 10.1002/advs.202410506.

Single Cell mass spectrometry: Towards quantification of small molecules in individual cells.

Lan Y, Zou Z, Yang Z Trends Analyt Chem. 2024; 174.

PMID: 39391010 PMC: 11465888. DOI: 10.1016/j.trac.2024.117657.

Recent Developments in Machine Learning for Mass Spectrometry.

Beck A, Muhoberac M, Randolph C, Beveridge C, Wijewardhane P, Kenttamaa H ACS Meas Sci Au. 2024; 4(3):233-246.

PMID: 38910862 PMC: 11191731. DOI: 10.1021/acsmeasuresciau.3c00060.

Single Cell Analysis of Proteoforms.

Su P, Hollas M, Butun F, Kanchustambham V, Rubakhin S, Ramani N J Proteome Res. 2024; 23(6):1883-1893.

PMID: 38497708 PMC: 11406863. DOI: 10.1021/acs.jproteome.4c00075.

References

Comi T, Neumann E, Do T, Sweedler J . microMS: A Python Platform for Image-Guided Mass Spectrometry Profiling. J Am Soc Mass Spectrom. 2017; 28(9):1919-1928. PMC: 5711600. DOI: 10.1007/s13361-017-1704-1. View

Spraggins J, Djambazova K, Rivera E, Migas L, Neumann E, Fuetterer A . High-Performance Molecular Imaging with MALDI Trapped Ion-Mobility Time-of-Flight (timsTOF) Mass Spectrometry. Anal Chem. 2019; 91(22):14552-14560. PMC: 7382025. DOI: 10.1021/acs.analchem.9b03612. View

Peng H, Xie P, Liu L, Kuang X, Wang Y, Qu L . Morphological diversity of single neurons in molecularly defined cell types. Nature. 2021; 598(7879):174-181. PMC: 8494643. DOI: 10.1038/s41586-021-03941-1. View

Wolf F, Angerer P, Theis F . SCANPY: large-scale single-cell gene expression data analysis. Genome Biol. 2018; 19(1):15. PMC: 5802054. DOI: 10.1186/s13059-017-1382-0. View

Lake B, Ai R, Kaeser G, Salathia N, Yung Y, Liu R . Neuronal subtypes and diversity revealed by single-nucleus RNA sequencing of the human brain. Science. 2016; 352(6293):1586-90. PMC: 5038589. DOI: 10.1126/science.aaf1204. View

Zhu Y, Piehowski P, Zhao R, Chen J, Shen Y, Moore R . Nanodroplet processing platform for deep and quantitative proteome profiling of 10-100 mammalian cells. Nat Commun. 2018; 9(1):882. PMC: 5830451. DOI: 10.1038/s41467-018-03367-w. View

Rompp A, Schramm T, Hester A, Klinkert I, Both J, Heeren R . imzML: Imaging Mass Spectrometry Markup Language: A common data format for mass spectrometry imaging. Methods Mol Biol. 2010; 696:205-24. DOI: 10.1007/978-1-60761-987-1_12. View

Becht E, McInnes L, Healy J, Dutertre C, Kwok I, Ng L . Dimensionality reduction for visualizing single-cell data using UMAP. Nat Biotechnol. 2018; . DOI: 10.1038/nbt.4314. View

Lombard-Banek C, Moody S, Nemes P . Single-Cell Mass Spectrometry for Discovery Proteomics: Quantifying Translational Cell Heterogeneity in the 16-Cell Frog (Xenopus) Embryo. Angew Chem Int Ed Engl. 2016; 55(7):2454-8. PMC: 4755155. DOI: 10.1002/anie.201510411. View

10.

Zhang L, Vertes A . Single-Cell Mass Spectrometry Approaches to Explore Cellular Heterogeneity. Angew Chem Int Ed Engl. 2017; 57(17):4466-4477. DOI: 10.1002/anie.201709719. View

11.

Kiselev V, Andrews T, Hemberg M . Challenges in unsupervised clustering of single-cell RNA-seq data. Nat Rev Genet. 2019; 20(5):273-282. DOI: 10.1038/s41576-018-0088-9. View

12.

Castro D, Xie Y, Rubakhin S, Romanova E, Sweedler J . Image-guided MALDI mass spectrometry for high-throughput single-organelle characterization. Nat Methods. 2021; 18(10):1233-1238. PMC: 8490150. DOI: 10.1038/s41592-021-01277-2. View

13.

Scigelova M, Hornshaw M, Giannakopulos A, Makarov A . Fourier transform mass spectrometry. Mol Cell Proteomics. 2011; 10(7):M111.009431. PMC: 3134075. DOI: 10.1074/mcp.M111.009431. View

14.

Phares G, Lloyd P . Purification, primary structure, and neuronal localization of cerebral peptide 1 from Aplysia. Peptides. 1996; 17(5):753-61. DOI: 10.1016/0196-9781(96)00081-2. View

15.

Yang J, Rubel O, Prabhat , Mahoney M, Bowen B . Identifying important ions and positions in mass spectrometry imaging data using CUR matrix decompositions. Anal Chem. 2015; 87(9):4658-66. DOI: 10.1021/ac5040264. View

16.

Xie Y, Castro D, Bell S, Rubakhin S, Sweedler J . Single-Cell Classification Using Mass Spectrometry through Interpretable Machine Learning. Anal Chem. 2020; 92(13):9338-9347. PMC: 7374983. DOI: 10.1021/acs.analchem.0c01660. View

17.

Argelaguet R, Cuomo A, Stegle O, Marioni J . Computational principles and challenges in single-cell data integration. Nat Biotechnol. 2021; 39(10):1202-1215. DOI: 10.1038/s41587-021-00895-7. View

18.

Oomen P, Aref M, Kaya I, Phan N, Ewing A . Chemical Analysis of Single Cells. Anal Chem. 2018; 91(1):588-621. DOI: 10.1021/acs.analchem.8b04732. View

19.

Shaw J, Lin T, Leach 3rd F, Tolmachev A, Tolic N, Robinson E . 21 Tesla Fourier Transform Ion Cyclotron Resonance Mass Spectrometer Greatly Expands Mass Spectrometry Toolbox. J Am Soc Mass Spectrom. 2016; 27(12):1929-1936. DOI: 10.1007/s13361-016-1507-9. View

20.

Molyneaux B, Arlotta P, Menezes J, Macklis J . Neuronal subtype specification in the cerebral cortex. Nat Rev Neurosci. 2007; 8(6):427-37. DOI: 10.1038/nrn2151. View