Scop3P : a comprehensive resource of human phosphosites within their full context

Protein phosphorylation is a key post-translational modification in many biological processes and is associated to human diseases such as cancer and metabolic disorders. The accurate identification, annotation, and functional analysis of phosphosites are therefore crucial to understand their various roles. Phosphosites are mainly analyzed through phosphoproteomics, which has led to increasing amounts of publicly available phosphoproteomics data. Several resources have been built around the resulting phosphosite information, but these are usually restricted to the protein sequence and basic site metadata. What is often missing from these resources, however, is context, including protein structure mapping, experimental provenance information, and biophysical predictions. We therefore developed Scop3P: a comprehensive database of human phosphosites within their full context. Scop3P integrates sequences (UniProtKB/Swiss-Prot), structures (PDB), and uniformly reprocessed phosphoproteomics data (PRIDE) to annotate all known human phosphosites. Furthermore, these sites are put into biophysical context by annotating each phosphoprotein with per-residue structural propensity, solvent accessibility, disordered probability, and early folding information. Scop3P, available at https://iomics.ugent.be/scop3p, presents a unique resource for visualization and analysis of phosphosites and for understanding of phosphosite structure–function relationships

Ionbot : a novel, innovative and sensitive machine learning approach to LC-MS/MS peptide identification

Mass spectrometry-based proteomics generates vast amounts of signal data that require computational interpretation to obtain peptide identifications. Dozens of algorithms for this task exist, but all exploit only part of the acquired data to judge a peptide-to-spectrum match (PSM), ignoring important information such as the observed retention time and fragment ion peak intensity pattern. Moreover, only few identification algorithms allow open modification searches that can substantially increase peptide identifications. We here therefore introduce ionbot, a novel open modification search engine that is the first to fully merge machine learning with peptide identification. This core innovation brings the ability to include a much larger range of experimental data into PSM scoring, and even to adapt this scoring to the specifics of the data itself. As a result, ionbot substantially increases PSM confidence for open searches, and even enables a further increase in peptide identification rate of up to 30% by also considering highly plausible, lower-ranked, co-eluting matches for a fragmentation spectrum. Moreover, the exclusive use of machine learning for scoring also means that any future improvements to predictive models for peptide behavior will also result in more sensitive and accurate peptide identification

PDBe-KB: collaboratively defining the biological context of structural data

none71: The Protein Data Bank in Europe - Knowledge Base (PDBe-KB, https://pdbe-kb.org) is an open collaboration between world-leading specialist data resources contributing functional and biophysical annotations derived from or relevant to the Protein Data Bank (PDB). The goal of PDBe-KB is to place macromolecular structure data in their biological context by developing standardised data exchange formats and integrating functional annotations from the contributing partner resources into a knowledge graph that can provide valuable biological insights. Since we described PDBe-KB in 2019, there have been significant improvements in the variety of available annotation data sets and user functionality. Here, we provide an overview of the consortium, highlighting the addition of annotations such as predicted covalent binders, phosphorylation sites, effects of mutations on the protein structure and energetic local frustration. In addition, we describe a library of reusable web-based visualisation components and introduce new features such as a bulk download data service and a novel superposition service that generates clusters of superposed protein chains weekly for the whole PDB archive.noneVaradi, Mihaly; Anyango, Stephen; Armstrong, David; Berrisford, John; Choudhary, Preeti; Deshpande, Mandar; Nadzirin, Nurul; Nair, Sreenath S; Pravda, Lukas; Tanweer, Ahsan; Al-Lazikani, Bissan; Andreini, Claudia; Barton, Geoffrey J; Bednar, David; Berka, Karel; Blundell, Tom; Brock, Kelly P; Carazo, Jose Maria; Damborsky, Jiri; David, Alessia; Dey, Sucharita; Dunbrack, Roland; Recio, Juan Fernandez; Fraternali, Franca; Gibson, Toby; Helmer-Citterich, Manuela; Hoksza, David; Hopf, Thomas; Jakubec, David; Kannan, Natarajan; Krivak, Radoslav; Kumar, Manjeet; Levy, Emmanuel D; London, Nir; Macias, Jose Ramon; Srivatsan, Madhusudhan M; Marks, Debora S; Martens, Lennart; McGowan, Stuart A; McGreig, Jake E; Modi, Vivek; Parra, R Gonzalo; Pepe, Gerardo; Piovesan, Damiano; Prilusky, Jaime; Putignano, Valeria; Radusky, Leandro G; Ramasamy, Pathmanaban; Rausch, Atilio O; Reuter, Nathalie; Rodriguez, Luis A; Rollins, Nathan J; Rosato, Antonio; Rubach, Paweł; Serrano, Luis; Singh, Gulzar; Skoda, Petr; Sorzano, Carlos Oscar S; Stourac, Jan; Sulkowska, Joanna I; Svobodova, Radka; Tichshenko, Natalia; Tosatto, Silvio C E; Vranken, Wim; Wass, Mark N; Xue, Dandan; Zaidman, Daniel; Thornton, Janet; Sternberg, Michael; Orengo, Christine; Velankar, SameerVaradi, Mihaly; Anyango, Stephen; Armstrong, David; Berrisford, John; Choudhary, Preeti; Deshpande, Mandar; Nadzirin, Nurul; Nair, Sreenath S; Pravda, Lukas; Tanweer, Ahsan; Al-Lazikani, Bissan; Andreini, Claudia; Barton, Geoffrey J; Bednar, David; Berka, Karel; Blundell, Tom; Brock, Kelly P; Carazo, Jose Maria; Damborsky, Jiri; David, Alessia; Dey, Sucharita; Dunbrack, Roland; Recio, Juan Fernandez; Fraternali, Franca; Gibson, Toby; Helmer-Citterich, Manuela; Hoksza, David; Hopf, Thomas; Jakubec, David; Kannan, Natarajan; Krivak, Radoslav; Kumar, Manjeet; Levy, Emmanuel D; London, Nir; Macias, Jose Ramon; Srivatsan, Madhusudhan M; Marks, Debora S; Martens, Lennart; Mcgowan, Stuart A; Mcgreig, Jake E; Modi, Vivek; Parra, R Gonzalo; Pepe, Gerardo; Piovesan, Damiano; Prilusky, Jaime; Putignano, Valeria; Radusky, Leandro G; Ramasamy, Pathmanaban; Rausch, Atilio O; Reuter, Nathalie; Rodriguez, Luis A; Rollins, Nathan J; Rosato, Antonio; Rubach, Paweł; Serrano, Luis; Singh, Gulzar; Skoda, Petr; Sorzano, Carlos Oscar S; Stourac, Jan; Sulkowska, Joanna I; Svobodova, Radka; Tichshenko, Natalia; Tosatto, Silvio C E; Vranken, Wim; Wass, Mark N; Xue, Dandan; Zaidman, Daniel; Thornton, Janet; Sternberg, Michael; Orengo, Christine; Velankar, Samee