An individualized protein-based prognostic model to stratify pediatric patients with papillary thyroid carcinoma.

Pediatric papillary thyroid carcinomas (PPTCs) exhibit high inter-tumor heterogeneity and currently lack widely adopted recurrence risk stratification criteria. Hence, we propose a machine learning-based objective method to individually predict their recurrence risk. We retrospectively collect and evaluate the clinical factors and proteomes of 83 pediatric benign (PB), 85 pediatric malignant (PM) and 66 adult malignant (AM) nodules, and quantify 10,426 proteins by mass spectrometry. We find 243 and 121 significantly dysregulated proteins from PM vs. PB and PM vs. AM, respectively. Function and pathway analyses show the enhanced activation of the inflammatory and immune system in PM patients compared with the others. Nineteen proteins are selected to predict recurrence using a machine learning model with an accuracy of 88.24%. Our study generates a protein-based personalized prognostic prediction model that can stratify PPTC patients into high- or low-recurrence risk groups, providing a reference for clinical decision-making and individualized treatment.

Comparative Evaluation of Proteome Discoverer and FragPipe for the TMT-Based Proteome Quantification.

Isobaric labeling-based proteomics is widely applied in deep proteome quantification. Among the platforms for isobaric labeled proteomic data analysis, the commercial software Proteome Discoverer (PD) is widely used, incorporating the search engine CHIMERYS, while FragPipe (FP) is relatively new, free for noncommercial purposes, and integrates the engine MSFragger. Here, we compared PD and FP over three public proteomic data sets labeled using 6plex, 10plex, and 16plex tandem mass tags. Our results showed the protein abundances generated by the two software are highly correlated. PD quantified more proteins (10.02%, 15.44%, 8.19%) than FP with comparable NA ratios (0.00% vs. 0.00%, 0.85% vs. 0.38%, and 11.74% vs. 10.52%) in the three data sets. Using the 16plex data set, PD and FP outputs showed high consistency in quantifying technical replicates, batch effects, and functional enrichment in differentially expressed proteins. However, FP saved 93.93%, 96.65%, and 96.41% of processing time compared to PD for analyzing the three data sets, respectively. In conclusion, while PD is a well-maintained commercial software integrating various additional functions and can quantify more proteins, FP is freely available and achieves similar output with a shorter computational time. Our results will guide users in choosing the most suitable quantification software for their needs.