A Completely Reimplemented MPI Bioinformatics Toolkit with a New HHpred Server at its Core

Post-transcriptional gene regulation (PTGR) concerns processes involved in the maturation, transport, stability and translation of coding and non-coding RNAs. RNA-binding proteins (RBPs) and ribonucleoproteins coordinate RNA processing and PTGR. The introduction of large-scale quantitative methods, such as next-generation sequencing and modern protein mass spectrometry, has renewed interest in the investigation of PTGR and the protein factors involved at a systems-biology level. Here, we present a census of 1,542 manually curated RBPs that we have analysed for their interactions with different classes of RNA, their evolutionary conservation, their abundance and their tissue-specific expression. Our analysis is a critical step towards the comprehensive characterization of proteins involved in human RNA metabolism.

/pdf/a-census-of-human-rna-binding-proteins-1mii7pfs5y.pdf

A census of human RNA-binding proteins.

Potent Neutralizing Antibodies against SARS-CoV-2 Identified by High-Throughput Single-Cell Sequencing of Convalescent Patients' B Cells.

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. We additionally discuss any new software, the new hardware infrastructure, our webservices and web site. Lastly we survey updates to some of the key predictive algorithms available through our website.

The PSIPRED Protein Analysis Workbench: 20 years on.

The origin and cellular complexity of eukaryotes represent a major enigma in biology. Current data support scenarios in which an archaeal host cell and an alphaproteobacterial (mitochondrial) endosymbiont merged together, resulting in the first eukaryotic cell. The host cell is related to Lokiarchaeota, an archaeal phylum with many eukaryotic features. The emergence of the structural complexity that characterizes eukaryotic cells remains unclear. Here we describe the 'Asgard' superphylum, a group of uncultivated archaea that, as well as Lokiarchaeota, includes Thor-, Odin- and Heimdallarchaeota. Asgard archaea affiliate with eukaryotes in phylogenomic analyses, and their genomes are enriched for proteins formerly considered specific to eukaryotes. Notably, thorarchaeal genomes encode several homologues of eukaryotic membrane-trafficking machinery components, including Sec23/24 and TRAPP domains. Furthermore, we identify thorarchaeal proteins with similar features to eukaryotic coat proteins involved in vesicle biogenesis. Our results expand the known repertoire of 'eukaryote-specific' proteins in Archaea, indicating that the archaeal host cell already contained many key components that govern eukaryotic cellular complexity.

/pdf/asgard-archaea-illuminate-the-origin-of-eukaryotic-cellular-3q3aexzc7f.pdf

Asgard archaea illuminate the origin of eukaryotic cellular complexity

Phyre2 is a web-based tool for predicting and analyzing protein structure and function. Phyre2 uses advanced remote homology detection methods to build 3D models, predict ligand binding sites, and analyze amino acid variants in a protein sequence. Phyre2 is a suite of tools available on the web to predict and analyze protein structure, function and mutations. The focus of Phyre2 is to provide biologists with a simple and intuitive interface to state-of-the-art protein bioinformatics tools. Phyre2 replaces Phyre, the original version of the server for which we previously published a paper in Nature Protocols. In this updated protocol, we describe Phyre2, which uses advanced remote homology detection methods to build 3D models, predict ligand binding sites and analyze the effect of amino acid variants (e.g., nonsynonymous SNPs (nsSNPs)) for a user's protein sequence. Users are guided through results by a simple interface at a level of detail they determine. This protocol will guide users from submitting a protein sequence to interpreting the secondary and tertiary structure of their models, their domain composition and model quality. A range of additional available tools is described to find a protein structure in a genome, to submit large number of sequences at once and to automatically run weekly searches for proteins that are difficult to model. The server is available at http://www.sbg.bio.ic.ac.uk/phyre2
 . A typical structure prediction will be returned between 30 min and 2 h after submission.

/pdf/the-phyre2-web-portal-for-protein-modeling-prediction-and-xppnx59tej.pdf

The Phyre2 web portal for protein modeling, prediction and analysis

PhyreRisk: A Dynamic Web Application to Bridge Genomics, Proteomics and 3D Structural Data to Guide Interpretation of Human Genetic Variants

http://spiral.imperial.ac.uk/bitstream/10044/1/27480/11/1-s2.0-S0022283615006105-main.pdf

PhyreStorm: A web server for fast structural searches against the PDB.

/pdf/phyre-and-phyrerisk-integrating-genetic-variant-data-with-ml5p68mwea.pdf

Stefans Mezulis

Papers

The Phyre2 web portal for protein modeling, prediction and analysis

PhyreRisk: A Dynamic Web Application to Bridge Genomics, Proteomics and 3D Structural Data to Guide Interpretation of Human Genetic Variants

PhyreStorm: A web server for fast structural searches against the PDB.

Phyre and PhyreRisk – Integrating genetic variant data with experimental and predicted protein structures and their complexes