Spatial Proteomics & MALDI-MSI

Advancing digital pathology and biomarker discovery through Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging (MALDI-MSI) and machine learning.

Spatial Proteomics combined with MALDI-MSI offers an unprecedented, label-free approach to mapping molecular distributions directly within intact tissue architectures.

Our research leverages high-resolution mass spectrometry imaging to extract complex molecular fingerprints from tissue samples. By coupling these massive proteomic datasets with advanced computational pathology and machine learning algorithms, we identify novel biomarkers, distinguish challenging tumor histologies, and uncover the distinct pathogenic pathways driving disease progression.

Spatial Proteomics MALDI-MSI Computational Pathology

The Power of Mass Spectrometry Imaging

Traditional histology relies heavily on morphology, which can sometimes result in ambiguous diagnoses for borderline or highly heterogeneous lesions. MALDI-MSI bridges the gap between molecular biology and morphology by maintaining the spatial context of proteins, peptides, and metabolites.

The core advantages of our approach include:

  • Untargeted Discovery: Unlike immunohistochemistry, MALDI-MSI does not require a priori knowledge of the target. We can analyze hundreds of molecules simultaneously in a single tissue section.
  • Morphological Correlation: Extracted mass spectra are directly mapped to specific regions of interest (ROIs) annotated by expert pathologists, linking pure molecular data to histological ground truth.
  • Diagnostic Precision: By identifying unique spatial proteomic signatures, we can stratify tumor subtypes, assess mutational statuses (e.g., NRAS mutations), and minimize diagnostic uncertainty.

Our Research Focus & Methodologies

Across multiple ongoing studies, our group develops and applies robust statistical and machine learning frameworks to handle the high dimensionality of MALDI-MSI data.

  • Feature Selection & Classification: We employ supervised and unsupervised machine learning models to sift through thousands of signals. This allows us to isolate the most impactful proteomic features responsible for disease classification.
  • Translational Biomarker Identification: Once key spatial signals are isolated, we utilize nanoscale liquid chromatography electrospray ionization tandem mass spectrometry (nLC-ESI-MS/MS) to confidently identify the underlying proteins, translating raw signals into actionable biological insights.
  • Multi-Tissue Applications: While we have extensively applied these pipelines to indeterminate thyroid neoplasms, our computational workflows are designed to be scalable and adaptable to a wide range of oncological and pathological challenges.

Research Highlights

High-Throughput MSI

Utilizing state-of-the-art MALDI-TOF/TOF systems to extract spatially resolved molecular features directly from tissue microarrays and whole slides.

AI-Driven Discovery

Applying dimensionality reduction and classification algorithms to decode complex molecular spectra into reliable diagnostic models.

Clinical Translation

Bridging the gap between untargeted omics and digital pathology to provide reliable ancillary tools for personalized medicine.

Core Publication

2026

  1. Improving the Annotation for Spatial Proteomics: A Computational Approach to Enhance Molecular Characterization of Thyroid Nodules
    Vasco Coelho, Nicole Monza, Natalia S Porto, and 4 more authors
    Journal of Proteome Research, 2026
  2. Spatial Proteomics Uncovers Region-Specific Proteomic Signatures in Autoimmune Liver Diseases
    Elisa Merelli, Vanna Denti, Giulia Capitoli, and 8 more authors
    Digestive and Liver Disease, 2026

2025

  1. Well begun Is half done: The impact of pre-processing in MALDI mass spectrometry imaging analysis applied to a case study of thyroid nodules
    Giulia Capitoli, Kirsten CJ Abeelen, Isabella Piga, and 4 more authors
    Stats, 2025
  2. Machine Learning ensemble algorithms for classification of thyroid nodules through proteomics: Extending the method of Shapley values from binary to multi-class tasks
    Giulia Capitoli, Simone Magnaghi, Andrea D’Amicis, and 6 more authors
    Stats, 2025
  3. Biomarker identification through spatial proteomics for the characterization of indeterminate thyroid nodules
    Giulia Capitoli, Antonio Maria Alviano, Nicole Monza, and 8 more authors
    Endocrine, 2025

2024

  1. MALDI-MS imaging in niftp diagnosis: an alternative approach
    Fabio Pagni, Angela Greco, Vanna Denti, and 7 more authors
    In Endocrine Abstracts, 2024
  2. Spatial resolution of renal amyloid deposits through MALDI-MSI: a combined digital and molecular approach to monoclonal gammopathies
    Greta Bindi, Andrew Smith, Glenda Oliveira, and 8 more authors
    Journal of Clinical Pathology, 2024

2023

  1. Unsupervised neural networks as a support tool for pathology diagnosis in MALDI-MSI experiments: A case study on thyroid biopsies
    Marco S Nobile, Giulia Capitoli, Virgil Sowirono, and 8 more authors
    Expert Systems with Applications, 2023
  2. Segmenting Brain MALDI-MSI Data Under Separate Exchangeability
    Francesco Denti, Cecilia Balocchi, and Giulia Capitoli
    In Interational Conference on Bayesian Young Statistician Meeting, 2023

2021

  1. Lipidomic typing of colorectal cancer tissue containing tumour-infiltrating lymphocytes by MALDI mass spectrometry imaging
    Vanna Denti, Allia Mahajneh, Giulia Capitoli, and 8 more authors
    Metabolites, 2021

2020

  1. Molecular trait of follicular-patterned thyroid neoplasms defined by MALDI-imaging
    Isabella Piga, Giulia Capitoli, Francesca Clerici, and 8 more authors
    Biochimica et Biophysica Acta (BBA)-Proteins and Proteomics, 2020
  2. Analysis of Hashimoto’s thyroiditis on fine needle aspiration samples by MALDI-Imaging
    Giulia Capitoli, Isabella Piga, Francesca Clerici, and 8 more authors
    Biochimica et Biophysica Acta (BBA)-Proteins and Proteomics, 2020

2019

  1. Molecular signatures of medullary thyroid carcinoma by matrix-assisted laser desorption/ionisation mass spectrometry imaging
    Andrew Smith, Manuel Galli, Isabella Piga, and 8 more authors
    Journal of proteomics, 2019
  2. Feasibility study for the MALDI-MSI analysis of thyroid fine needle aspiration biopsies: evaluating the morphological and proteomic stability over time
    Isabella Piga, Giulia Capitoli, Silvia Tettamanti, and 8 more authors
    PROTEOMICS–Clinical Applications, 2019