A5089774776- Advanced Proteomics Techniques and Applications
- RNA and protein synthesis mechanisms
- Protein Structure and Dynamics
- Mass Spectrometry Techniques and Applications
- Computational Drug Discovery Methods
- Bacterial Genetics and Biotechnology
- Ubiquitin and proteasome pathways
- Protein Degradation and Inhibitors
- Bioinformatics and Genomic Networks
- Machine Learning in Bioinformatics
- Genomics and Chromatin Dynamics
- Hydrocarbon exploration and reservoir analysis
- Gene expression and cancer classification
- RNA Research and Splicing
- Histone Deacetylase Inhibitors Research
- Chemical Synthesis and Analysis
- Endoplasmic Reticulum Stress and Disease
- Geological Formations and Processes Exploration
- RNA modifications and cancer
- ATP Synthase and ATPases Research
- Genomics and Phylogenetic Studies
- SARS-CoV-2 and COVID-19 Research
- Viral Infectious Diseases and Gene Expression in Insects
- Advanced Biosensing Techniques and Applications
- Data-Driven Disease Surveillance
European Molecular Biology Laboratory
2018-2024
European Molecular Biology Laboratory
2018-2022
European Molecular Biology Organization
2018-2021
Heidelberg University
2014-2021
German Cancer Research Center
2015-2017
European Molecular Biology Laboratory
2017
University of Oxford
2016
MRC Brain Network Dynamics Unit
2016
Medical Research Council
2016
Heidelberg University
2014
Abstract A better understanding of proteostasis in health and disease requires robust methods to determine protein half-lives. Here we improve the precision accuracy peptide ion intensity-based quantification, enabling more accurate turnover determination non-dividing cells by dynamic SILAC-based proteomics. This approach allows exact half-lives ranging from 10 >1000 h. We identified 4000–6000 proteins several cell types, corresponding 9699 unique identifications over entire data set....
Abstract Adenosine triphosphate (ATP) plays fundamental roles in cellular biochemistry and was recently discovered to function as a biological hydrotrope. Here, we use mass spectrometry interrogate ATP-mediated regulation of protein thermal stability solubility on proteome-wide scale. Thermal proteome profiling reveals high affinity interactions ATP substrate an allosteric modulator that has widespread influence complexes their stability. Further, develop strategy for profiling, discover...
Article24 July 2018Open Access Transparent process Thermal proteome profiling in bacteria: probing protein state vivo André Mateus orcid.org/0000-0001-6870-0677 Genome Biology Unit, European Molecular Laboratory, Heidelberg, Germany Search for more papers by this author Jacob Bobonis Faculty of Biosciences, Heidelberg University, Nils Kurzawa orcid.org/0000-0002-7846-2817 Frank Stein Proteomics Core Facility, Dominic Helm Johannes Hevler Athanasios Typas Corresponding Author [email...
ChIP-seq has become a widely adopted genomic assay in recent years to determine binding sites for transcription factors or enrichments specific histone modifications. Beside detection of enriched bound regions, an important question is differences between conditions. While this common analysis gene expression, which large number computational approaches have been validated, the same particularly challenging owing complexity data terms noisiness and variability. Many different tools developed...
Detecting the targets of drugs and other molecules in intact cellular contexts is a major objective drug discovery biology more broadly. Thermal proteome profiling (TPP) pursues this aim at proteome-wide scale by inferring target engagement from its effects on temperature-dependent protein denaturation. However, key challenge TPP statistical analysis measured melting curves with controlled false rates high coverage detection power. We present nonparametric response (NPARC), method for based...
Abstract Reversible protein phosphorylation is an important mechanism for regulating (dis)assembly of biomolecular condensates. However, condensate-specific phosphosites remain largely unknown, thereby limiting our understanding the underlying mechanisms. Here, we combine solubility proteome profiling with phosphoproteomics to quantitatively map several hundred enriched in either soluble or condensate-bound subpopulations, including a subset modulating protein–RNA interactions. We show that...
Abstract The complexity of the functional proteome extends considerably beyond coding genome, resulting in millions proteoforms. Investigation proteoforms and their roles is important to understand cellular physiology its deregulation diseases but challenging perform systematically. Here we applied thermal profiling with deep peptide coverage detect proteoform groups acute lymphoblastic leukemia cell lines different cytogenetic aberrations. We detected 15,846 proteoforms, capturing...
The phosphatases PP1 and PP2A are responsible for the majority of dephosphorylation reactions on phosphoserine (pSer) phosphothreonine (pThr), involved in virtually all cellular processes numerous diseases. catalytic subunits exist cells form holoenzymes, which impart substrate specificity. contribution to recognition substrates is unclear. By developing a phosphopeptide library approach phosphoproteomic assay, we demonstrate that specificity holoenzymes towards pThr basic motifs adjacent...
Detecting ligand-protein interactions in living cells is a fundamental challenge molecular biology and drug research. Proteome-wide profiling of thermal stability as function ligand concentration promises to tackle this challenge. However, current data analysis strategies use preset thresholds that can lead suboptimal sensitivity/specificity tradeoffs limited comparability across datasets. Here, we present method based on statistical hypothesis testing curves, which provides control the...
Production of indigoidine can be enhanced by swapping a synthetic T domain into the NRPS IndC.
Protein aggregates have negative implications in disease. While reductionist experiments increased our understanding of aggregation processes, the systemic view biological context is still limited. To extend this understanding, we used mass spectrometry-based proteomics to characterize and disaggregation human cells after non-lethal heat shock. Aggregation-prone proteins were enriched nuclear proteins, high proportion intrinsically disordered regions, molecular mass, isoelectric point,...
Article16 February 2021Open Access Transparent process SARS-CoV-2 infection remodels the host protein thermal stability landscape Joel Selkrig orcid.org/0000-0003-2977-4408 Genome Biology Unit, European Molecular Laboratory (EMBL), Heidelberg, GermanyThese authors contributed equally to this work Search for more papers by author Megan Stanifer orcid.org/0000-0002-5606-1297 Department of Infectious Diseases, Virology, Heidelberg University Hospital, André Mateus orcid.org/0000-0001-6870-0677...
Rtpca is an R package implementing methods for inferring protein-protein interactions (PPIs) based on thermal proteome profiling experiments of a single condition or in differential setting via approach called proximity coaggregation. It offers user-friendly tools to explore datasets their PPI predictive performance and easily integrates with available packages.Rtpca from Bioconductor (https://bioconductor.org/packages/Rtpca).Supplementary data are at Bioinformatics online.
Single-gene deletions can affect the expression levels of other genes in same operon bacterial genomes. Here, we used proteomics for 133 Escherichia coli gene deletion mutants and transcriptome sequencing (RNA-seq) data from 71 to probe extent transcriptional post-transcriptional effects operons. Transcriptional were common on located downstream consistent across all members, with nearly 40% operons showing greater than 2-fold up- or downregulation. Surprisingly, observed an additional...
Summary Reversible protein phosphorylation regulates virtually every cellular process and is arguably the most well-studied post-translational modification. Still, less than 3% of sites identified in humans have annotated functions. Functionally-relevant are known to trigger conformational changes proteins and/or regulate their interactions with other proteins, nucleic acids small molecules - all which can be reflected thermal stability a protein. Thus, combining proteome profiling (TPP)...
Abstract Non-negative matrix factorization (NMF) has been widely used for the analysis of genomic data to perform feature extraction and signature identification due interpretability decomposed signatures. However, running a basic NMF requires installation multiple tools dependencies, along with steep learning curve computing time. To mitigate such obstacles, we developed ShinyButchR, novel R/Shiny application that provides complete NMF-based workflow, allowing user decomposition using NMF,...
Abstract Metazoans are crucially dependent on multiple layers of gene regulatory mechanisms which allow them to control expression across developmental stages, tissues and cell types. Multiple recent research consortia have aimed generate comprehensive datasets profile the activity these type- condition-specific landscapes many different lines primary cells. However, extraction genes or elements specific certain entities from remains challenging. We here propose a novel method based...