Aggregated Molecular Phenotype Scores: Enhancing Assessment and Visualization of Mass Spectrometry Imaging Data for Tissue-Based Diagnostics

Authors

Jessie R Chappel
Mary E King
Jonathon Fleming
Livia S Eberlin
David M Reif
Erin S Baker

Publication Date

8-29-2023

Journal

Analytical Chemistry

DOI

10.1021/acs.analchem.3c02389

PMID

37579019

PMCID

PMC10561690

PubMedCentral® Posted Date

10-9-2023

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Humans, Diagnostic Imaging, Spectrometry, Mass, Electrospray Ionization, Neoplasms, Metabolomics, Phenotype, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Molecular Imaging

Abstract

Mass spectrometry imaging (MSI) has gained increasing popularity for tissue-based diagnostics due to its ability to identify and visualize molecular characteristics unique to different phenotypes within heterogeneous samples. Data from MSI experiments are often assessed and visualized using various supervised and unsupervised statistical approaches. However, these approaches tend to fall short in identifying and concisely visualizing subtle, phenotype-relevant molecular changes. To address these shortcomings, we developed aggregated molecular phenotype (AMP) scores. AMP scores are generated using an ensemble machine learning approach to first select features differentiating phenotypes, weight the features using logistic regression, and combine the weights and feature abundances. AMP scores are then scaled between 0 and 1, with lower values generally corresponding to class 1 phenotypes (typically control) and higher scores relating to class 2 phenotypes. AMP scores, therefore, allow the evaluation of multiple features simultaneously and showcase the degree to which these features correlate with various phenotypes. Due to the ensembled approach, AMP scores are able to overcome limitations associated with individual models, leading to high diagnostic accuracy and interpretability. Here, AMP score performance was evaluated using metabolomic data collected from desorption electrospray ionization MSI. Initial comparisons of cancerous human tissues to their normal or benign counterparts illustrated that AMP scores distinguished phenotypes with high accuracy, sensitivity, and specificity. Furthermore, when combined with spatial coordinates, AMP scores allow visualization of tissue sections in one map with distinguished phenotypic borders, highlighting their diagnostic utility.