A network module for the perseus software for computational proteomics facilitates proteome interaction graph analysis

Proteomics data analysis strongly benefits from not studying single proteins in isolation but taking their multivariate interdependence into account. We introduce PerseusNet, the new Perseus network module for the biological analysis of proteomics data. Proteomics is commonly used to generate networks, e.g., with affinity purification experiments, but networks are also used to explore proteomics data. PerseusNet supports the biomedical researcher for both modes of data analysis with a multitude of activities. For affinity purification, a volcano-plot-based statistical analysis method for network generation is featured which is scalable to large numbers of baits. For posttranslational modifications of proteins, such as phosphorylation, a collection of dedicated network analysis tools helps in elucidating cellular signaling events. Co-expression network analysis of proteomics data adopts established tools from transcriptome co-expression analysis. PerseusNet is extensible through a plugin architecture in a multi-lingual way, integrating analyses in C#, Python, and R, and is freely available at http://www.perseus-framework.org.publishedVersio

Accurate and Automated High-Coverage Identification of Chemically Cross-Linked Peptides with MaxLynx

Cross-linking combined with mass spectrometry (XL-MS) provides a wealth of information about the three-dimensional (3D) structure of proteins and their interactions. We introduce MaxLynx, a novel computational proteomics workflow for XL-MS integrated into the MaxQuant environment. It is applicable to noncleavable and MS-cleavable cross-linkers. For both, we have generalized the Andromeda peptide database search engine to efficiently identify cross-linked peptides. For noncleavable peptides, we implemented a novel dipeptide Andromeda score, which is the basis for a computationally efficient N-squared search engine. Additionally, partial scores summarize the evidence for the two constituents of the dipeptide individually. A posterior error probability (PEP) based on total and partial scores is used to control false discovery rates (FDRs). For MS-cleavable cross-linkers, a score of signature peaks is combined with the conventional Andromeda score on the cleavage products. The MaxQuant 3D peak detection was improved to ensure more accurate determination of the monoisotopic peak of isotope patterns for heavy molecules, which cross-linked peptides typically are. A wide selection of filtering parameters can replace the manual filtering of identifications, which is often necessary when using other pipelines. On benchmark data sets of synthetic peptides, MaxLynx outperforms all other tested software on data for both types of cross-linkers and on a proteome-wide data set of cross-linked Drosophila melanogaster cell lysate. The workflow also supports ion mobility-enhanced MS data. MaxLynx runs on Windows and Linux, contains an interactive viewer for displaying annotated cross-linked spectra, and is freely available at https://www.maxquant.org/.publishedVersio

Continuous families of isospectral Heisenberg spin systems and the limits of inference from measurements

We investigate classes of quantum Heisenberg spin systems which have different coupling constants but the same energy spectrum and hence the same thermodynamical properties. To this end we define various types of isospectrality and establish conditions for their occurence. The triangle and the tetrahedron whose vertices are occupied by spins 1/2 are investigated in some detail. The problem is also of practical interest since isospectrality presents an obstacle to the experimental determination of the coupling constants of small interacting spin systems such as magnetic molecules

On Cox rings of K3-surfaces

We study Cox rings of K3-surfaces. A first result is that a K3-surface has a finitely generated Cox ring if and only if its effective cone is polyhedral. Moreover, we investigate degrees of generators and relations for Cox rings of K3-surfaces of Picard number two, and explicitly compute the Cox rings of generic K3-surfaces with a non-symplectic involution that have Picard number 2 to 5 or occur as double covers of del Pezzo surfaces.Comment: minor corrections, to appear in Compositio Mathematica, 32 page

Role for ribosome-associated quality control in sampling proteins for MHC class I-mediated antigen presentation

Pathogens and tumors are detected by the immune system through the display of intracellular peptides on MHC-I complexes. These peptides are generated by the ubiquitin−proteasome system preferentially from newly synthesized polypeptides. Here we show that the ribosome-associated quality control (RQC) pathway, responsible for proteasomal degradation of polypeptide chains that stall during translation, mediates efficient antigen presentation of model proteins independent of their intrinsic folding properties. Immunopeptidome characterization of RQC-deficient cells shows that RQC contributes to the presentation of a wide variety of proteins, including proteins that may otherwise evade presentation due to efficient folding. By identifying endogenous substrates of the RQC pathway in human cells, our results also enable the analysis of common principles causing ribosome stalling under physiological conditions.publishedVersio

Securin Is Not Required for Chromosomal Stability in Human Cells

Abnormalities of chromosome number are frequently observed in cancers. The mechanisms regulating chromosome segregation in human cells are therefore of great interest. Recently it has been reported that human cells without an hSecurin gene lose chromosomes at a high frequency. Here we show that, after hSecurin knockout through homologous recombination, chromosome losses are only a short, transient effect. After a few passages hSecurin(−/−) cells became chromosomally stable and executed mitoses normally. This was unexpected, as the securin loss resulted in a persisting reduction of the sister-separating protease separase and inefficient cleavage of the cohesin subunit Scc1. Our data demonstrate that securin is dispensable for chromosomal stability in human cells. We propose that human cells possess efficient mechanisms to compensate for the loss of genes involved in chromosome segregation

A novel chromatographic method allows online reanalyses in proteomic investigations and acquiring more information from biological samples

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