SFLD (Structure-Function Linkage Database) is a hierarchical classification of enzymes that relates specific sequence-structure features to specific chemical capabilities.

NCBIfam is a collection of protein families, featuring curated multiple sequence alignments, hidden Markov models (HMMs) and annotation, which provides a tool for identifying functionally related proteins based on sequence homology. NCBIfam is maintained at the National Center for Biotechnology Information (Bethesda, MD). NCBIfam includes models from TIGRFAMs, another database of protein families developed at The Institute for Genomic Research, then at the J. Craig Venter Institute (Rockville, MD, US).

SUPERFAMILY is a library of profile hidden Markov models that represent all proteins of known structure. The library is based on the SCOP classification of proteins: each model corresponds to a SCOP domain and aims to represent the entire SCOP superfamily that the domain belongs to. SUPERFAMILY is based at the University of Bristol, UK.

SMART (a Simple Modular Architecture Research Tool) allows the identification and annotation of genetically mobile domains and the analysis of domain architectures. SMART is based at EMBL, Heidelberg, Germany.

HAMAP stands for High-quality Automated and Manual Annotation of Proteins. HAMAP profiles are manually created by expert curators. They identify proteins that are part of well-conserved protein families or subfamilies. HAMAP is based at the SIB Swiss Institute of Bioinformatics, Geneva, Switzerland.

This project contains raw data, intermediate files and results used to create the integrated map of protein expression in human cancer (including data from cell lines and tumours). The map is based on joint reanalysis of 11 large-scale quantitative proteomics studies. The datasets were primarily retrieved from the PRIDE database, as well as MassIVE database and CPTAC data portal. The raw files were manually curated in order to capture mass spectrometry acquisition parameters, experimental design and sample characteristics. The raw files were jointly processed with MaxQuant computational platform using standard settings (see Data Processing Protocol). Due to size of the data, the processing was done in two batches denoted as “celllines” and “tumours” analysis. In total, using a 1% peptide spectrum match and protein false discovery rates, the analysis allowed identification of 21,580 protein groups in the cell lines dataset (MQ search results available in ‘txt-celllines’ folder), and 13,441 protein groups in the tumours dataset (MQ search results available in ‘txt-tumours’ folder).

Basal expression profiles of 1,000 human cancer cell lines in the Genomics of Drug Sensitivity in Cancer (GDSC) panel [upcoming version], profiled using a diverse collection of 265 compounds. We have carried out an extensive computational exploration of the data to determine (1) to what extent does the mutational landscape of cancer cell lines recapitulate that seen in primary tumours, (2) what effect the status of these genomic features have on the variation in drug response; (3) whether genomic alterations acting in concert explain more of the variation in drug response; and (4) what is the predictive ability of these individual data-omics and at what extent this is improved when they are combined. [See publication]

We generated a systematic, quantitative and deep proteome and transcriptome abundance atlas from 29 paired healthy human to serve as a molecular baseline to study human biology.

Partial remission (PR) occurs in only half of patients with new-onset type 1 diabetes (T1D) and correspond to a transient period characterized by low daily insulin needs, low glycemic fluctuations and increased endogenous insulin secretion. While identification of newly-onset T1D patients with significant residual beta-cell function may foster patient-specific interventions, reliable predictive biomarkers of PR occurrence currently lack. We analyzed the plasma of children with new-onset T1D to identify biomarkers present at diagnosis that predicted PR at 3 months post-diagnosis. We first performed an extensive shotgun proteomic analysis using Liquid Chromatography-Tandem-Mass-Spectrometry (LCMS/MS) on the plasma of 16 children with new-onset T1D and quantified nearly 1500 unique proteins with 98 significantly correlating with Insulin-Dose Adjusted glycated hemoglobin A1c score (IDAA1C). We next applied a series of both qualitative and statistical filters that yielded to the selection of 26 protein candidates that were associated to pathophysiological mechanisms related to T1D. Finally, we translationally validated several of the candidates using single-shot targeted proteomic (PRM method) on raw plasma. Taken together, we identified plasmatic biomarkers present at diagnosis that may predict the occurrence of PR in a single mass-spectrometry run. We believe that the identification of new predictive biomarkers of PR and β-cell function is key to stratify patients with new-onset T1D for β-cell preservation therapies

Here, we apply a recently-developed approach for de novo protein structure determination based on the incorporation of short-distance crosslinking data as constraints in discrete molecular dynamics simulations (CL-DMD), for the determination of the conformational ensemble of tau protein in solution. The predicted structure may facilitate an understanding of the misfolding and oligomerization pathways of the tau protein.

We describe a single-step centrifugal elutriation method to produce synchronous G1-phase procyclic trypanosomes at a scale amenable for proteomic analysis of the cell cycle. Using ten-plex tandem mass tag technology, we quantified 5,325 proteins across the cell cycle in this parasite, providing a useful resource for the scientific community. Of these, 384 proteins were classified as cell cycle regulated and these were subdivided into nine distinct clusters of temporal regulation. A number of known cell cycle regulators in trypanosomes were detected in these groups, validating our approach, as well as forty novel and essential cell cycle regulated proteins that could be considered as future drug targets. Through cross-comparison to the TrypTag microscopy database, we were able to validate the cell cycle regulated patterns of expression for many of these proteins of unknown function. A convenient interface to access and interrogate these data is also presented.

We sequence mRNA from single mESCs from three culture conditions: serum + LIF, 2i + LIF and alternative 2i + LIF. We extensively analysed population and single cell gene expression to identify differences and similarities between conditions. This is a subset of data from ArrayExpress accession E-ERAD-186 (ENA: ERP003293)

Beta cells within the pancreatic islet represent a heterogenous population wherein individual sub-groups of cells make distinct contributions to the overall control of insulin secretion. These include a subpopulation of highly-connected ‘hub’ cells, important for the propagation of intercellular Ca2+ waves. Functional subpopulations have also been demonstrated in human beta cells, with an altered subtype distribution apparent in type 2 diabetes. At present, the molecular mechanisms through which beta cell hierarchy is established are poorly understood. Changes at the level of the epigenome provide one such possibility which we explore here by focussing on the imprinted gene neuronatin(Nnat), which is required for normal insulin synthesis and secretion.

Not available

The biological process of RNA translation is fundamental to cellular life and has wide-ranging implications for human disease. Yet, accurately delineating the variation in RNA translation represents a significant challenge. Here, we develop RiboTIE, a transformer model-based approach to map global RNA translation. We find that RiboTIE offers unparalleled precision and sensitivity for ribosome profiling data. Application of RiboTIE to normal brain and medulloblastoma cancer samples enables high-resolution insights into disease regulation of RNA translation.

This dataset covers the development of 7 organs (brain, cerebellum, heart, kidney, liver, ovary and testis) from 4 weeks post conception to adulthood (including ageing).

Alternative splicing, a fundamental step in gene expression, is deregulated in many diseases. Splicing factors (SFs), which regulate this process, are up- or down regulated or mutated in several diseases including cancer. To date, there are no inhibitors that directly inhibit the activity of SFs. We designed decoy oligonucleotides, composed of several repeats of a RNA motif, which is recognized by a single SF. Here we show that decoy oligonucleotides targeting splicing factors RBFOX1/2, SRSF1 and PTBP1, can specifically bind to their respective SFs and inhibit their splicing and biological activities both in vitro and in vivo. These decoy oligonucleotides present a novel approach to specifically downregulate SF activity and have the potential to treat diseases where SFs are up-regulated, such as cancer.

Quantitative study of the N-terminal acetylome variations in Arabidopsis thaliana, looking at the effect of a N-acetyltransferase KO.

Dynamic proteins and multi-protein complexes govern most biological processes. Cross-linking/mass spectrometry (CLMS) is increasingly successful in providing residue-resolution data on static proteinaceous structures. In order to investigate the technical feasibility of recording dynamic processes using isotope-labelling for quantitation, we generated a model dataset by cross-linking human serum albumin (HSA) with the readily available cross-linker BS3-d0/d4 in different heavy/light ratios.

Bacterial meningitis is usually fatal without treatment and prompt and accurate diagnosis coupled with the timely administration of parenteral antibiotics, are necessary in order to save lives. The diagnosis can sometimes be delayed whilst samples are analysed in a laboratory using traditional methods of microscopy and antigen testing. The objective of our project is to define specific protein signatures in cerebrospinal fluid associated with Streptococcus pneumoniae infection which could lead to the development of assays or point-of-care devices to improve the speed and accuracy of diagnosis, and guide the clinicians in the treatment and prognosis of children with bacterial meningitis. The associated research paper is in preparation.