Rapid Multivariate Analysis Approach to Explore Differential Spatial Protein Profiles in Tissue.

Autor:	Sharman K; Mass Spectrometry Research Center, Vanderbilt University, Nashville, Tennessee 37235, United States.; Program in Chemical & Physical Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States., Patterson NH; Mass Spectrometry Research Center, Vanderbilt University, Nashville, Tennessee 37235, United States.; Department of Biochemistry, Vanderbilt University, Nashville, Tennessee 37232, United States., Weiss A; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee 37212, United States., Neumann EK; Mass Spectrometry Research Center, Vanderbilt University, Nashville, Tennessee 37235, United States.; Department of Biochemistry, Vanderbilt University, Nashville, Tennessee 37232, United States., Guiberson ER; Mass Spectrometry Research Center, Vanderbilt University, Nashville, Tennessee 37235, United States.; Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235, United States., Ryan DJ; Pfizer Inc., Chesterfield, Missouri 63017, United States., Gutierrez DB; Mass Spectrometry Research Center, Vanderbilt University, Nashville, Tennessee 37235, United States., Spraggins JM; Mass Spectrometry Research Center, Vanderbilt University, Nashville, Tennessee 37235, United States.; Department of Biochemistry, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235, United States.; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee 37235, United States., Van de Plas R; Mass Spectrometry Research Center, Vanderbilt University, Nashville, Tennessee 37235, United States.; Department of Biochemistry, Vanderbilt University, Nashville, Tennessee 37232, United States.; Delft Center for Systems and Control, Delft University of Technology, 2628 CD Delft, The Netherlands., Skaar EP; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee 37212, United States.; Department of Medicine, Vanderbilt University, Nashville, Tennessee 37232, United States., Caprioli RM; Mass Spectrometry Research Center, Vanderbilt University, Nashville, Tennessee 37235, United States.; Department of Biochemistry, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235, United States.; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232, United States.
Jazyk:	angličtina
Zdroj:	Journal of proteome research [J Proteome Res] 2023 May 05; Vol. 22 (5), pp. 1394-1405. Date of Electronic Publication: 2022 Jul 18.
DOI:	10.1021/acs.jproteome.2c00206
Abstrakt:	Spatially targeted proteomics analyzes the proteome of specific cell types and functional regions within tissue. While spatial context is often essential to understanding biological processes, interpreting sub-region-specific protein profiles can pose a challenge due to the high-dimensional nature of the data. Here, we develop a multivariate approach for rapid exploration of differential protein profiles acquired from distinct tissue regions and apply it to analyze a published spatially targeted proteomics data set collected from Staphylococcus aureus -infected murine kidney, 4 and 10 days postinfection. The data analysis process rapidly filters high-dimensional proteomic data to reveal relevant differentiating species among hundreds to thousands of measured molecules. We employ principal component analysis (PCA) for dimensionality reduction of protein profiles measured by microliquid extraction surface analysis mass spectrometry. Subsequently, k -means clustering of the PCA-processed data groups samples by chemical similarity. Cluster center interpretation revealed a subset of proteins that differentiate between spatial regions of infection over two time points. These proteins appear involved in tricarboxylic acid metabolomic pathways, calcium-dependent processes, and cytoskeletal organization. Gene ontology analysis further uncovered relationships to tissue damage/repair and calcium-related defense mechanisms. Applying our analysis in infectious disease highlighted differential proteomic changes across abscess regions over time, reflecting the dynamic nature of host-pathogen interactions.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu