PhosphoSitePlus, 2014: mutations, PTMs and recalibrations.

Area of Science:

• Biochemistry
• Genomics
• Bioinformatics

Background:

• Mammalian post-translational modifications (PTMs) are crucial for cellular processes.
• PhosphoSitePlus (PSP) is a comprehensive database of PTMs, primarily derived from mass spectrometry (MS).
• Ensuring data reliability in large PTM datasets is essential for biological research.

Purpose of the Study:

• To improve the reliability of existing mass spectrometry data in the PhosphoSitePlus database.
• To introduce new curated datasets for enhanced data utility.
• To identify and characterize PTMs impacted by genetic variants (PTMVars) and their potential roles in disease.

Main Methods:

• Reanalysis of over 1,000,000 mass spectrometry spectra using a common analysis standard.
• Filtering of site assignments with P > 0.05 to enhance data quality.
• Integration of missense mutation data from UniPROTKB, TCGA, and other sources with PTM data.

Main Results:

• Over 330,000 non-redundant PTMs are available in PSP, with >95% from MS experiments.
• Reanalysis improved data reliability by applying consistent standards and filtering low-confidence sites.
• Two new datasets were released: 'Regulatory sites' and 'PTMVar', identifying over 25,000 PTMVars.
• PTMVars link missense mutations to over 2000 diseases and hundreds of cancers, including specific counts for phosphorylation, ubiquitylation, acetylation, methylation, and succinylation sites.

Conclusions:

• The reanalysis of MS data significantly enhances the reliability of the PhosphoSitePlus PTM database.
• The new 'Regulatory sites' and 'PTMVar' datasets provide valuable resources for understanding PTM regulation and variant-associated diseases.
• PTMVars represent a critical intersection of genetic variation and PTMs, offering insights into signaling pathway rewiring and disease mechanisms.