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Protein phosphorylation is one of the most abundant reversible post-translational modifications in eukaryotes. It is involved in virtually all cellular processes by regulating protein function, localization and stability and by mediating protein-protein interactions. Furthermore, aberrant protein phosphorylation is implicated in the onset and progression of human diseases such as cancer and neurodegenerative disorders. In the last years, tens of thousands of in vivo phosphorylation events have been identified by large-scale quantitative phospho-proteomics experiment suggesting that a large fraction of the proteome might be regulated by phosphorylation. This data explosion is increasingly enabling the development of computational approaches, often combined with experimental validation, aiming at prioritizing phosphosites and assessing their functional relevance. Some computational approaches also address the inference of specificity determinants of protein kinases/phosphatases and the identification of phosphoresidue recognition domains. In this context, several challenging issues are still open regarding phosphorylation, including a better understanding of the interplay between phosphorylation and allosteric regulation, agents and mechanisms disrupting or promoting abnormal phosphorylation in diseases, the identification and modulation of novel phosphorylation inhibitors, and so forth. Furthermore, the determinants of kinase and phosphatase recognition and binding specificity are still unknown in several cases, as well as the impact of disease mutations on phosphorylation-mediated signaling. The articles included in this Research Topic illustrate the very diverse aspects of phosphorylation, ranging from structural changes induced by phosphorylation to the peculiarities of phosphosite evolution. Some also provide a glimpse into the huge complexity of phosphorylation networks and pathways in health and disease, and underscore that a deeper knowledge of such processes is essential to identify disease biomarkers, on one hand, and design more effective therapeutic strategies, on the other.

Background A large number of PROSITE patterns select false positives and/or miss known true positives. It is possible that – at least in some cases – the weak specificity and/or sensitivity of a pattern is due to the fact that one, or maybe more, functional and/or structural key residues are not represented in the pattern. Multiple sequence alignments are commonly used to build functional sequence patterns. If residues structurally conserved in proteins sharing a function cannot be aligned in a multiple sequence alignment, they are likely to be missed in a standard pattern construction procedure. Results Here we present a new procedure aimed at improving the sensitivity and/ or specificity of poorly-performing patterns. The procedure can be summarised as follows: 1. residues structurally conserved in different proteins, that are true positives for a pattern, are identified by means of a computational technique and by visual inspection. 2. the sequence positions of the structurally conserved residues falling outside the pattern are used to build extended sequence patterns. 3. the extended patterns are optimised on the SWISS-PROT database for their sensitivity and specificity. The method was applied to eight PROSITE patterns. Whenever structurally conserved residues are found in the surface region close to the pattern (seven out of eight cases), the addition of information inferred from structural analysis is shown to improve pattern selectivity and in some cases selectivity and sensitivity as well. In some of the cases considered the procedure allowed the identification of functionally interesting residues, whose biological role is also discussed. Conclusion Our method can be applied to any type of functional motif or pattern (not only PROSITE ones) which is not able to select all and only the true positive hits and for which at least two true positive structures are available. The computational technique for the identification of structurally conserved residues is already available on request and will be soon accessible on our web server. The procedure is intended for the use of pattern database curators and of scientists interested in a specific protein family for which no specific or selective patterns are yet available.

Contains fulltext : 171819.pdf (Publisher’s version ) (Open Access) Life sciences are yielding huge data sets that underpin scientific discoveries fundamental to improvement in human health, agriculture and the environment. In support of these discoveries, a plethora of databases and tools are deployed, in technically complex and diverse implementations, across a spectrum of scientific disciplines. The corpus of documentation of these resources is fragmented across the Web, with much redundancy, and has lacked a common standard of information. The outcome is that scientists must often struggle to find, understand, compare and use the best resources for the task at hand.Here we present a community-driven curation effort, supported by ELIXIR-the European infrastructure for biological information-that aspires to a comprehensive and consistent registry of information about bioinformatics resources. The sustainable upkeep of this Tools and Data Services Registry is assured by a curation effort driven by and tailored to local needs, and shared amongst a network of engaged partners.As of November 2015, the registry includes 1785 resources, with depositions from 126 individual registrations including 52 institutional providers and 74 individuals. With community support, the registry can become a standard for dissemination of information about bioinformatics resources: we welcome everyone to join us in this common endeavour. The registry is freely available at https://bio.tools.

Relatively few protein structures are known, compared to the enormous amount of sequence data produced in the sequencing of different genomes, and relatively few protein complexes are deposited in the PDB with respect to the great amount of interaction data coming from high-throughput experiments (two-hybrid or affinity purification of protein complexes and mass spectrometry). Nevertheless, we can rely on computational techniques for the extraction of high-quality and information-rich data from the known structures and for their spreading in the protein sequence space. We describe here the ongoing research projects in our group: we analyse the protein complexes stored in the PDB and, for each complex involving one domain belonging to a family of interaction domains for which some interaction data are available, we can calculate its probability of interaction with any protein sequence. We analyse the structures of proteins encoding a function specified in a PROSITE pattern, which exhibits relatively low selectivity and specificity, and build extended patterns. To this aim, we consider residues that are well-conserved in the structure, even if their conservation cannot easily be recognized in the sequence alignment of the proteins holding the function. We also analyse protein surface regions and, through the annotation of the solvent-exposed residues, we annotate protein surface patches via a structural comparison performed with stringent parameters and independently of the residue order in the sequence. Local surface comparison may also help in identifying new sequence patterns, which could not be highlighted with other sequence-based methods. © 2003 John Wiley & Sons, Ltd.

Summary: Rapid technological advances have led to an explosion of biomedical data in recent years. The pace of change has inspired new collaborative approaches for sharing materials and resources to help train life scientists both in the use of cutting-edge bioinformatics tools and databases and in how to analyse and interpret large datasets. A prototype platform for sharing such training resources was recently created by the Bioinformatics Training Network (BTN). Building on this work, we have created a centralized portal for sharing training materials and courses, including a catalogue of trainers and course organizers, and an announcement service for training events. For course organizers, the portal provides opportunities to promote their training events; for trainers, the portal offers an environment for sharing materials, for gaining visibility for their work and promoting their skills; for trainees, it offers a convenient one-stop shop for finding suitable training resources and identifying relevant training events and activities locally and worldwide. Availability and implementation: http://mygoblet.org/training-portal Contact: manuel.corpas@tgac.ac.uk