Modified DecisionTree with Custom Splitting LogicImproves Generalization across Multiple Brains’ Proteomic DataSets of Alzheimer’s Disease

Many factors negatively affect a generalization of the findings in discovery proteomics. They include differentiation between patient cohorts, a variety of experimental conditions, etc. We presented a machine-learning-based workflow for proteomics data analysis, aiming at improving generalizability across multiple data sets. In particular, we customized the decision tree model by introducing a new parameter, min_groups_leaf, which regulates the presence of the samples from each data set inside the model’s leaves. Further, we analyzed a trend for the feature importance’s curve as a function of the novel parameter for feature selection to a list of proteins with significantly improved generalization. The developed workflow was tested using five proteomic data sets obtained for post-mortem human brain samples of Alzheimer’s disease. The data sets consisted of 535 LC–MS/MS acquisition files. The results were obtained for two different pipelines of data processing: (1) MS1-only processing based on DirectMS1 search engine and (2) a standard MS/MS-based one. Using the developed workflow, we found seven proteins with expression patterns that were unique for asymptomatic Alzheimer patients. Two of them, Serotransferrin TRFE and DNA repair nuclease APEX1, may be potentially important for explaining the lack of dementia in patients with the presence of neuritic plaques and neurofibrillary tangles.