A5013130910- Mass Spectrometry Techniques and Applications
- Metabolomics and Mass Spectrometry Studies
- Advanced Proteomics Techniques and Applications
- Spectroscopy and Chemometric Analyses
- Spectroscopy Techniques in Biomedical and Chemical Research
- Analytical Chemistry and Chromatography
- Endometriosis Research and Treatment
- Nuclear Physics and Applications
- Ion-surface interactions and analysis
- Infrared Thermography in Medicine
- Reproductive System and Pregnancy
- Cell Image Analysis Techniques
- AI in cancer detection
- Health, Environment, Cognitive Aging
- Isotope Analysis in Ecology
- Single-cell and spatial transcriptomics
- Molecular Biology Techniques and Applications
- Radiomics and Machine Learning in Medical Imaging
- Bioinformatics and Genomic Networks
- Endometrial and Cervical Cancer Treatments
- Renal and related cancers
- Uterine Myomas and Treatments
- Cancer Genomics and Diagnostics
- Chronic Kidney Disease and Diabetes
- Glycosylation and Glycoproteins Research
Delft University of Technology
2016-2025
Vanderbilt University
2016-2025
Vanderbilt University Medical Center
2015-2021
Fund for Scientific Research
2012
KU Leuven
2006-2010
Oulu University Hospital
2007
Transformative technologies are enabling the construction of three dimensional (3D) maps tissues with unprecedented spatial and molecular resolution. Over next seven years, NIH Common Fund Human Biomolecular Atlas Program (HuBMAP) intends to develop a widely accessible framework for comprehensively mapping human body at single-cell resolution by supporting technology development, data acquisition, detailed mapping. HuBMAP will integrate its efforts other funding agencies, programs,...
Zinc co-crystallizes with insulin in dense core secretory granules, but its role biosynthesis, storage and secretion is unknown. In this study we assessed the of zinc transporter ZnT8 using ZnT8-knockout ( −/− ) mice. Absence expression caused loss release upon stimulation exocytosis, normal rates content preserved glucose-induced release. Ultrastructurally, mature granules were rare beta cells replaced by immature, pale “progranules,” which larger than +/+ islets. When mice fed a control...
Imaging mass spectrometry (IMS) enables the spatially targeted molecular assessment of biological tissues at cellular resolutions. New developments and technologies are essential for uncovering drivers native physiological function disease. Instrumentation must maximize spatial resolution, throughput, sensitivity, specificity, because tissue imaging experiments consist thousands to millions pixels. Here, we report development application a matrix-assisted laser desorption/ionization (MALDI)...
Non‐small cell lung cancer (NSCLC) is the leading cause of death globally. To develop better diagnostics and more effective treatments, research in past decades has focused on identification molecular changes genome, transcriptome, proteome, recently also metabolome. Phospholipids, which nevertheless play a central role functioning, remain poorly explored. Here, using mass spectrometry (MS)‐based phospholipidomics approach, we profiled 179 phospholipid species malignant matched non‐malignant...
Tensor completion recently emerged as a generalization of matrix for higher order arrays. This problem formulation allows one to exploit the structure data that intrinsically have multiple dimensions. In this work, we recall convex minimum (multilinear) ranks arrays arbitrary order. Successively focus on partially observed spectral images; latter can be naturally represented third tensors and typically exhibit intraband correlations. We compare different formulations assess them through case studies.
The correlation of imaging mass spectrometry (IMS) with histopathology can help relate novel molecular findings obtained through IMS to the well-characterized and validated knowledge base. quality between these two modalities is limited by spatial mapping that registration image types. In this work, we develop workflows for MALDI IMS-to-microscopy data analysis using nondestructive IMS-compatible wide field autofluorescence (AF) microscopy combined computational registration. First, a...
Lipids are a structurally diverse class of molecules with important biological functions including cellular signaling and energy storage. Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) allows for direct mapping biomolecules in tissues. Fully characterizing the structural diversity lipids remains challenge due to presence isobaric isomeric species, which greatly complicates data interpretation when only m/z information is available. Integrating ion...
Multimodal imaging by matrix-assisted laser desorption ionisation mass spectrometry (MALDI MSI) and microscopy holds potential for understanding pathological mechanisms mapping molecular signatures from the tissue microenvironment to specific cell populations. However, existing software solutions MALDI MSI data analysis are incomplete, require programming skills contain laborious manual steps, hindering broadly applicable, reproducible, high-throughput generate impactful biological...
An early semi-invasive diagnosis of endometriosis has the potential to allow treatment and minimize disease progression but no such test is available at present. Our aim was perform a combined mRNA microarray proteomic analysis on same eutopic endometrium sample obtained from patients with without endometriosis. protein fractions were extracted 49 endometrial biopsies women laparoscopically proven presence (n= 31) or absence 18) during luteal 27) menstrual phase 22) analyzed using surface...
Multimodal mass spectrometric imaging identifies bacterial and host analytes in intact tissues during invasive infection mice.
Low molecular weight metabolites are essential for defining the phenotypes of cells. However, spatial metabolomics tools often lack sensitivity, specify, and resolution to provide comprehensive descriptions these species in tissue. MALDI imaging mass spectrometry (IMS) low ions is particularly challenging as matrix clusters nominally isobaric with multiple metabolite ions, requiring high resolving power instrumentation or derivatization circumvent this issue. An alternative perform ion...
Lung cancer is the leading cause of death. Beyond first line treatment, few therapeutic options are available, particularly for squamous cell carcinoma (SCC). Here, we have explored phospholipidomes 30 human SCCs and found that they almost invariably (in 96.7% cases) contain phospholipids with longer acyl chains compared to matched normal tissues. This trait was confirmed using in situ 2D-imaging MS on tissue sections by phospholipidomics tumor lung L-IkkαKA/KA mouse model SCC. In both...
The glomerulus is a multicellular functional tissue unit (FTU) of the nephron that responsible for blood filtration. Each contains multiple substructures and cell types are crucial their function. To understand normal aging disease in kidneys, methods high spatial resolution molecular imaging within these FTUs across whole slide images required. Here we demonstrate workflow using microscopy-driven selected sampling to enable 5 μm pixel size matrix-assisted laser desorption/ionization mass...
Histology-directed imaging mass spectrometry (IMS) is a spatially targeted IMS acquisition method informed by expert annotation that provides rapid molecular characterization of select tissue structures. The annotations are usually determined on digital whole slide images histological stains where the staining preparation incompatible with optimal preparation, necessitating serial sections: one for annotation, IMS. Registration then used to align onto section. Herein, we report...
The molecular identification of species interest is an important part imaging mass spectrometry (IMS) experiment. high resolution accurate capabilities Fourier transform ion cyclotron resonance (FT-ICR MS) have recently been shown to facilitate the proteins in matrix-assisted laser desorption/ionization (MALDI) IMS. However, these experiments are typically limited giving rise ions relatively low m/ z due difficulties transmitting and measuring large weight charge states. Herein we modified...
The search for molecular species that are differentially expressed between biological states is an important step towards discovering promising biomarker candidates. In imaging mass spectrometry (IMS), performing this manually often impractical due to the large size and high-dimensionality of IMS datasets. Instead, we propose interpretable machine learning workflow automatically identifies candidates by their mass-to-charge ratios, quantitatively estimates relevance recognizing a given class...
Identifying the spatial distributions of biomolecules in tissue is crucial for understanding integrated function. Imaging mass spectrometry (IMS) allows simultaneous mapping thousands biosynthetic products such as lipids but has needed a means identifying specific cell-types or functional states to correlate with molecular localization. We report, here, advances starting from identity marking genetically encoded fluorophore. The fluorescence emission data were IMS through multimodal image...
Although Staphylococcus aureus is the leading cause of biofilm-related infections, lipidomic distributions within these biofilms poorly understood. Here, mapping S. biofilm cross-sections was performed to investigate heterogeneity between horizontal layers.S. were grown statically, embedded in a mixture carboxymethylcellulose/gelatin, and prepared for downstream matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS). Trapped ion mobility (TIMS) also applied prior...
We introduce the spiked mixture model (SMM) to address problem of estimating a set signals from many randomly scaled and noisy observations. Subsequently, we design novel expectation-maximization (EM) algorithm recover all parameters SMM. Numerical experiments show that in low signal-to-noise ratio regimes, for data types where SMM is relevant, surpasses more traditional Gaussian (GMM) terms signal recovery performance. The broad relevance its corresponding EM demonstrated by applying...
We have developed a new class of dual polarity molecules for matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) capable sub 10 µm spatial resolution on commercial instruments. Aminated cinnamic acid analogs (ACAA) were tested vacuum stability, absorption at 355 nm, crystal size, and molecular coverage. Among them, 4-aminocinnamic (ACA) 4-(dimethylamino)cinnamic (DMACA) found to perform similar or superior levels lipid IMS compared conventional MALDI matrices....