DeepPep: Deep proteome inference from peptide profiles

Protein inference, the identification of the protein set that is the origin of a given peptide profile, is a fundamental challenge in proteomics. We present DeepPep, a deep-convolutional neural network framework that predicts the protein set from a proteomics mixture, given the sequence universe of possible proteins and a target peptide profile. In its core, DeepPep quantifies the change in probabilistic score of peptide-spectrum matches in the presence or absence of a specific protein, hence selecting as candidate proteins with the largest impact to the peptide profile. Application of the method across datasets argues for its competitive predictive ability (AUC of 0.80±0.18, AUPR of 0.84±0.28) in inferring proteins without need of peptide detectability on which the most competitive methods rely. We find that the convolutional neural network architecture outperforms the traditional artificial neural network architectures without convolution layers in protein inference. We expect that similar deep learning architectures that allow learning nonlinear patterns can be further extended to problems in metagenome profiling and cell type inference. The source code of DeepPep and the benchmark datasets used in this study are available at https://deeppep.github.io/DeepPep/.Author Summary: The accurate identification of proteins in a proteomics sample, called the protein inference problem, is a fundamental challenge in biomedical sciences. Current approaches are based on applications of traditional neural networks, linear optimization and Bayesian techniques. We here present DeepPep, a deep-convolutional neural network framework that predicts the protein set from a standard proteomics mixture, given all protein sequences and a peptide profile. Comparison to leading methods shows that DeepPep has most robust performance with various instruments and datasets. Our results provide evidence that using sequence-level location information of a peptide in the context of proteome sequence can result in more accurate and robust protein inference. We conclude that Deep Learning on protein sequence leads to superior platforms for protein inference that can be further refined with additional features and extended for far reaching applications.