PT  - JOURNAL ARTICLE
AU  - John A. Bachman
AU  - Benjamin M. Gyori
AU  - Peter K. Sorger
TI  - Assembling a corpus of phosphoproteomic annotations using ProtMapper to normalize site information from databases and text mining
AID  - 10.1101/822668
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 822668
4099  - http://biorxiv.org/content/early/2019/10/29/822668.short
4100  - http://biorxiv.org/content/early/2019/10/29/822668.full
AB  - A major challenge in analyzing large phosphoproteomic datasets is that information on phosphorylating kinases and other upstream regulators is limited to a small fraction of phosphosites. One approach to addressing this problem is to aggregate and normalize information from all available information sources, including both curated databases and large-scale text mining. However, when we attempted to aggregate information on post-translational modifications (PTMs) from six databases and three text mining systems, we found that a substantial proportion of phosphosites were positioned on non-canonical residue positions. These errors were attributable to the use of residue numbers from non-canonical isoforms, mouse or rat proteins, post-translationally processed proteins and also from errors in curation and text mining. Published mass spectrometry datasets from large-scale efforts such as the Clinical Proteomic Tumor Analysis Consortium (CPTAC) also localize many PTMs to non-canonical sequences, precluding their accurate annotation. To address these problems, we developed ProtMapper, an open-source Python tool that automatically normalizes site positions to human protein reference sequences using data from PhosphoSitePlus and Uniprot. ProtMapper identifies valid reference positions with high precision and reasonable recall, making it possible to filter out machine reading errors from text mining and thereby assemble a corpus of 29,400 regulatory annotations for 13,668 sites, a 2.8-fold increase over PhosphoSitePlus, the current gold standard. To our knowledge this corpus represents the most comprehensive source of literature-derived information about phosphosite regulation currently available and its assembly illustrates the importance of sequence normalization. Combining the expanded corpus of annotations with normalization of CPTAC data nearly doubled the number of CPTAC annotated sites and the mean number of annotations per site. ProtMapper is available under an open source BSD 2-clause license at https://github.com/indralab/protmapper, and the corpus of phosphosite annotations is available as Supplementary Data with this paper under a CC-BY-NC-SA license. All results from the paper are reproducible from code available at https://github.com/johnbachman/protmapper_paper.