Deep learning for the PSIPRED Protein Analysis Workbench.

The PSIRED Workbench is a long established and popular bioinformatics web service offering a wide range of machine learning based analyses for characterizing protein structure and function. In this paper we provide an update of the recent additions and developments to the webserver, with a focus on new Deep Learning based methods. We briefly discuss some trends in server usage since the publication of AlphaFold2 and we give an overview of some upcoming developments for the service.

Improving cell type identification with Gaussian noise-augmented single-cell RNA-seq contrastive learning.

Cell type identification is an important task for single-cell RNA-sequencing (scRNA-seq) data analysis. Many prediction methods have recently been proposed, but the predictive accuracy of difficult cell type identification tasks is still low. In this work, we proposed a novel Gaussian noise augmentation-based scRNA-seq contrastive learning method (GsRCL) to learn a type of discriminative feature representations for cell type identification tasks.

Use of 3D Navigation Versus Traditional Fluoroscopy for Posterior Pelvic Ring Fixation.

Unstable pelvic ring disruption is most commonly treated with closed reduction and percutaneous screw fixation. Traditional methods involve screw placement under fluoroscopic imaging, but with recent technologic advances, intraoperative 3D navigation can now be used to help with the insertion of sacroiliac screws. Various cadaver studies have shown that placement of sacroiliac screws under 3D navigation is more accurate than placement under traditional fluoroscopic guidance.

The Genome3D Consortium for Structural Annotations of Selected Model Organisms.

Genome3D consortium is a collaborative project involving protein structure prediction and annotation resources developed by six world-leading structural bioinformatics groups, based in the United Kingdom (namely Blundell, Murzin, Gough, Sternberg, Orengo, and Jones). The main objective of Genome3D serves as a common portal to provide both predicted models and annotations of proteins in model organisms, using several resources developed by these labs such as CATH-Gene3D, DOMSERF, pDomTHREADER, PHYRE, SUPERFAMILY, FUGUE/TOCATTA, and VIVACE. These resources primarily use SCOP- and/or CATH-based protein domain assignments.

Genome3D: integrating a collaborative data pipeline to expand the depth and breadth of consensus protein structure annotation.

Genome3D (https://www.genome3d.eu) is a freely available resource that provides consensus structural annotations for representative protein sequences taken from a selection of model organisms.

Learning a functional grammar of protein domains using natural language word embedding techniques.

In this paper, using Word2vec, a widely-used natural language processing method, we demonstrate that protein domains may have a learnable implicit semantic "meaning" in the context of their functional contributions to the multi-domain proteins in which they are found. Word2vec is a group of models which can be used to produce semantically meaningful embeddings of words or tokens in a fixed-dimension vector space. In this work, we treat multi-domain proteins as "sentences" where domain identifiers are tokens which may be considered as "words.

The PSIPRED Protein Analysis Workbench: 20 years on.

The PSIPRED Workbench is a web server offering a range of predictive methods to the bioscience community for 20 years. Here, we present the work we have completed to update the PSIPRED Protein Analysis Workbench and make it ready for the next 20 years. The main focus of our recent website upgrade work has been the acceleration of analyses in the face of increasing protein sequence database size.

Isolated Treatment of a Comminuted Capitate Fracture: A Case Report.

Case: Comminuted fractures of the capitate, in the absence of associated carpal injuries, are exceedingly rare. Treatment of this complex injury is not well-documented in the literature. We describe the case of a comminuted capitate fracture that was successfully managed with Kirschner wire fixation.

Improved protein contact predictions with the MetaPSICOV2 server in CASP12.

In this paper, we present the results for the MetaPSICOV2 contact prediction server in the CASP12 community experiment (http://predictioncenter.org). Over the 35 assessed Free Modelling target domains the MetaPSICOV2 server achieved a mean precision of 43.

Predictions of Backbone Dynamics in Intrinsically Disordered Proteins Using De Novo Fragment-Based Protein Structure Predictions.

Intrinsically disordaered proteins (IDPs) are a prevalent phenomenon with over 30% of human proteins estimated to have long disordered regions. Computational methods are widely used to study IDPs, however, nearly all treat disorder in a binary fashion, not accounting for the structural heterogeneity present in disordered regions. Here, we present a new de novo method, FRAGFOLD-IDP, which addresses this problem.

EigenTHREADER: analogous protein fold recognition by efficient contact map threading.

Motivation: Protein fold recognition when appropriate, evolutionarily-related, structural templates can be identified is often trivial and may even be viewed as a solved problem. However in cases where no homologous structural templates can be detected, fold recognition is a notoriously difficult problem ( Moult et al., 2014 ).

Genome3D: exploiting structure to help users understand their sequences.

Genome3D (http://www.genome3d.eu) is a collaborative resource that provides predicted domain annotations and structural models for key sequences.

Scalable web services for the PSIPRED Protein Analysis Workbench.

Here, we present the new UCL Bioinformatics Group's PSIPRED Protein Analysis Workbench. The Workbench unites all of our previously available analysis methods into a single web-based framework. The new web portal provides a greatly streamlined user interface with a number of new features to allow users to better explore their results.

Protein function prediction by massive integration of evolutionary analyses and multiple data sources.

Background: Accurate protein function annotation is a severe bottleneck when utilizing the deluge of high-throughput, next generation sequencing data. Keeping database annotations up-to-date has become a major scientific challenge that requires the development of reliable automatic predictors of protein function. The CAFA experiment provided a unique opportunity to undertake comprehensive 'blind testing' of many diverse approaches for automated function prediction.

A large-scale evaluation of computational protein function prediction.

Automated annotation of protein function is challenging. As the number of sequenced genomes rapidly grows, the overwhelming majority of protein products can only be annotated computationally. If computational predictions are to be relied upon, it is crucial that the accuracy of these methods be high.

Genome3D: a UK collaborative project to annotate genomic sequences with predicted 3D structures based on SCOP and CATH domains.

Genome3D, available at http://www.genome3d.eu, is a new collaborative project that integrates UK-based structural resources to provide a unique perspective on sequence-structure-function relationships.

PSICOV: precise structural contact prediction using sparse inverse covariance estimation on large multiple sequence alignments.

Motivation: The accurate prediction of residue-residue contacts, critical for maintaining the native fold of a protein, remains an open problem in the field of structural bioinformatics. Interest in this long-standing problem has increased recently with algorithmic improvements and the rapid growth in the sizes of sequence families. Progress could have major impacts in both structure and function prediction to name but two benefits.

Predictions of hot spot residues at protein-protein interfaces using support vector machines.

Protein-protein interactions are critically dependent on just a few 'hot spot' residues at the interface. Hot spots make a dominant contribution to the free energy of binding and they can disrupt the interaction if mutated to alanine. Here, we present HSPred, a support vector machine(SVM)-based method to predict hot spot residues, given the structure of a complex.

Evolution of protein superfamilies and bacterial genome size.

We present the structural annotation of 56 different bacterial species based on the assignment of genes to 816 evolutionary superfamilies in the CATH domain structure database. These assignments have enabled us to analyse the recurrence of specific superfamilies within and across the genomes. We have selected the superfamilies that have a very broad representation and therefore appear to be universally distributed in a significant number of bacterial lineages.

A structural perspective on genome evolution.

Protein translations of over 100 complete genomes are now available. About half of these sequences can be provided with structural annotation, thereby enabling some profound insights into protein and pathway evolution. Whereas the major domain structure families are common to all kingdoms of life, these are combined in different ways in multidomain proteins to give various domain architectures that are specific to kingdoms or individual genomes, and contribute to the diverse phenotypes observed.

Gene3D: structural assignments for the biologist and bioinformaticist alike.

The Gene3D database (http://www.biochem.ucl.

Gene3D: structural assignment for whole genes and genomes using the CATH domain structure database.

We present a novel web-based resource, Gene3D, of precalculated structural assignments to gene sequences and whole genomes. This resource assigns structural domains from the CATH database to whole genes and links these to their curated functional and structural annotations within the CATH domain structure database, the functional Dictionary of Homologous Superfamilies (DHS) and PDBsum. Currently Gene3D provides annotation for 36 complete genomes (two eukaryotes, six archaea, and 28 bacteria).

The CATH extended protein-family database: providing structural annotations for genome sequences.

An automatic sequence search and analysis protocol (DomainFinder) based on PSI-BLAST and IMPALA, and using conservative thresholds, has been developed for reliably integrating gene sequences from GenBank into their respective structural families within the CATH domain database (http://www.biochem.ucl.

The CATH protein family database: a resource for structural and functional annotation of genomes.

Over the last decade, there have been huge increases in the numbers of protein sequences and structures determined. In parallel, many methods have been developed for recognising similarities between these proteins, arising from their common evolutionary background, and for clustering such relatives into protein families. Here we review some of the protein family resources available to the biologist and describe how these can be used to provide structural and functional annotations for newly determined sequences.