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The Impact of Histological Annotations for Accurate Tissue Classification Using Mass Spectrometry Imaging.

ABSTRACT: Knowing the precise location of analytes in the tissue has the potential to provide information about the organs' function and predict its behavior. It is especially powerful when used in diagnosis and prognosis prediction of pathologies, such as cancer. Spatial proteomics, in particular mass spectrometry imaging, together with machine learning approaches, has been proven to be a very helpful tool in answering some histopathology conundrums. To gain accurate information about the tissue, there is a need to build robust classification models. We have investigated the impact of histological annotation on the classification accuracy of different tumor tissues. Intrinsic tissue heterogeneity directly impacts the efficacy of the annotations, having a more pronounced effect on more heterogeneous tissues, as pancreatic ductal adenocarcinoma, where the impact is over 20% in accuracy. On the other hand, in more homogeneous samples, such as kidney tumors, histological annotations have a slenderer impact on the classification accuracy.

SUBMITTER: Goncalves JPL

PROVIDER: S-EPMC8624953 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The primary diagnosis of thyroid tumors based on histopathological patterns can be ambiguous in some cases, so proper classification of thyroid diseases might be improved if molecular biomarkers support cytological and histological assessment. In this work, tissue microarrays representative for major types of thyroid malignancies-papillary thyroid cancer (classical and follicular variant), follicular thyroid cancer, anaplastic thyroid cancer, and medullary thyroid cancer-and benign thyroid follicular adenoma and normal thyroid were analyzed by mass spectrometry imaging (MSI), and then different computation approaches were implemented to test the suitability of the registered profiles of tryptic peptides for tumor classification. Molecular similarity among all seven types of thyroid specimens was estimated, and multicomponent classifiers were built for sample classification using individual MSI spectra that corresponded to small clusters of cells. Moreover, MSI components showing the most significant differences in abundance between the compared types of tissues detected and their putative identity were established by annotation with fragments of proteins identified by liquid chromatography-tandem mass spectrometry in corresponding tissue lysates. In general, high accuracy of sample classification was associated with low inter-tissue similarity index and a high number of components with significant differences in abundance between the tissues. Particularly, high molecular similarity was noted between three types of tumors with follicular morphology (adenoma, follicular cancer, and follicular variant of papillary cancer), whose differentiation represented the major classification problem in our dataset. However, low level of the intra-tissue heterogeneity increased the accuracy of classification despite high inter-tissue similarity (which was exemplified by normal thyroid and benign adenoma). We compared classifiers based on all detected MSI components (n = 1536) and the subset of the most abundant components (n = 147). Despite relatively higher contribution of components with significantly different abundance and lower overall inter-tissue similarity in the latter case, the precision of classification was generally higher using all MSI components. Moreover, the classification model based on individual spectra (a single-pixel approach) outperformed the model based on mean spectra of tissue cores. Our result confirmed the high feasibility of MSI-based approaches to multi-class detection of cancer types and proved the good performance of sample classification based on individual spectra (molecular image pixels) that overcame problems related to small amounts of heterogeneous material, which limit the applicability of classical proteomics.

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The Impact of Histological Annotations for Accurate Tissue Classification Using Mass Spectrometry Imaging.

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