Dimension reduction techniques for the integrative analysis of multi-omics data.
Briefings in Bioinformatics 17(4):628 (2016)
State-of-the-art next-generation sequencing, transcriptomics, proteomics and other high-throughput 'omics' technologies enable the efficient generation of large experimental data sets. These data may yield unprecedented knowledge about molecular pathways in cells and their role in disease. Dimen...
Immunomodulatory drugs disrupt the cereblon-CD147-MCT1 axis to exert antitumor activity and teratogenicity.
Nature Medicine 22(7):735 (2016)
Immunomodulatory drugs (IMiDs), such as thalidomide and its derivatives lenalidomide and pomalidomide, are key treatment modalities for hematologic malignancies, particularly multiple myeloma (MM) and del(5q) myelodysplastic syndrome (MDS). Cereblon (CRBN), a substrate receptor of the CRL4 ubiqu...
Chemical Proteomics Reveals Ferrochelatase as a Common Off-target of Kinase Inhibitors.
ACS Chemical Biology 11(5):1245 (2016)
Many protein kinases are valid drug targets in oncology because they are key components of signal transduction pathways. The number of clinical kinase inhibitors is on the rise, but these molecules often exhibit polypharmacology, potentially eliciting desired and toxic effects. Therefore, a comp...
MALDI-TOF and nESI Orbitrap MS/MS identify orthogonal parts of the phosphoproteome.
Proteomics 16(10):1447 (2016)
Phosphorylation is a reversible posttranslational protein modification which plays a pivotal role in intracellular signaling. Despite extensive efforts, phosphorylation site mapping of proteomes is still incomplete motivating the exploration of alternative methods that complement existing workfl...
Towards Understanding Male Infertility After Spinal Cord Injury Using Quantitative Proteomics.
Molecular & Cellular Proteomics 15(4):1424 (2016)
The study of male infertility after spinal cord injury (SCI) has enhanced the understanding of seminal plasma (SP) as an important regulator of spermatozoa function. However, the most important factors leading to the diminished sperm motility and viability observed in semen of men with SCI remai...
moCluster: Identifying Joint Patterns Across Multiple Omics Data Sets.
Journal of Proteome Research 15(3):755 (2016)
Increasingly, multiple omics approaches are being applied to understand the complexity of biological systems. Yet, computational approaches that enable the efficient integration of such data are not well developed. Here, we describe a novel algorithm, termed moCluster, which discovers joint patt...
Translatomics combined with transcriptomics and proteomics reveals novel functional, recently evolved orphan genes in Escherichia coli O157:H7 (EHEC).
BMC Genomics 17(1):133 (2016)
Genomes of E. coli, including that of the human pathogen Escherichia coli O157:H7 (EHEC) EDL933, still harbor undetected protein-coding genes which, apparently, have escaped annotation due to their small size and non-essential function. To find such genes, global gene expression of EHEC EDL933 w...
Evaluation of Kinase Activity Profiling Using Chemical Proteomics.
ACS Chemical Biology 10(12):2743 (2015)
Protein kinases are important mediators of intracellular signaling and are reversibly activated by phosphorylation. Immobilized kinase inhibitors can be used to enrich these often low-abundance proteins, to identify targets of kinase inhibitors, or to probe their selectivity. It has been suggest...
Optimized Plk1 PBD Inhibitors Based on Poloxin Induce Mitotic Arrest and Apoptosis in Tumor Cells.
ACS Chemical Biology 10(11):2570 (2015)
Polo-like kinase 1 (Plk1) is a central regulator of mitosis and has been validated as a target for antitumor therapy. The polo-box domain (PBD) of Plk1 regulates its kinase activity and mediates the subcellular localization of Plk1 and its interactions with a subset of its substrates. Functional...
Inhibitor-based affinity probes for the investigation of JAK signaling pathways.
Proteomics 15(17):3066 (2015)
The Janus Kinase (JAK) signaling pathway plays a key role for many cellular processes and has recently been correlated with neuronal disorders. In order to understand new links of JAK family members with other signaling pathways, chemical proteomics tools with broad kinase coverage are desirable...
A Scalable Approach for Protein False Discovery Rate Estimation in Large Proteomic Data Sets.
Molecular & Cellular Proteomics 14(9):2394 (2015)
Calculating the number of confidently identified proteins and estimating false discovery rate (FDR) is a challenge when analyzing very large proteomic data sets such as entire human proteomes. Biological and technical heterogeneity in proteomic experiments further add to the challenge and there ...
Semi-supervised Learning Predicts Approximately One Third of the Alternative Splicing Isoforms as Functional Proteins.
Cell Reports 12(2):183 (2015)
Alternative splicing acts on transcripts from almost all human multi-exon genes. Notwithstanding its ubiquity, fundamental ramifications of splicing on protein expression remain unresolved. The number and identity of spliced transcripts that form stably folded proteins remain the sources of cons...
Chemical Proteomics Uncovers EPHA2 as a Mechanism of Acquired Resistance to Small Molecule EGFR Kinase Inhibition.
Journal of Proteome Research 14(6):2617 (2015)
Tyrosine kinase inhibitors (TKIs) have become an important therapeutic option for treating several forms of cancer. Gefitinib, an inhibitor of the epidermal growth factor receptor (EGFR), is in clinical use for treating non-small cell lung cancer (NSCLC) harboring activating EGFR mutations. Howe...
Molecular mechanisms behind the antimicrobial activity of hop iso-α-acids in Lactobacillus brevis.
Food Microbiology 46:553 (2015)
The main bittering component in beer, hop iso-α-acids, have been characterised as weak acids, which act as ionophores impairing microbial cells' function under acidic conditions as present in beer. Besides medium pH, divalent cations play a central role regarding the efficacy of the antimicrobia...
Optimized chemical proteomics assay for kinase inhibitor profiling.
Journal of Proteome Research 14(3):1574 (2015)
Solid supported probes have proven to be an efficient tool for chemical proteomics. The kinobeads technology features kinase inhibitors covalently attached to Sepharose for affinity enrichment of kinomes from cell or tissue lysates. This technology, combined with quantitative mass spectrometry, ...
DENEDDYLASE1 deconjugates NEDD8 from non-cullin protein substrates in Arabidopsis thaliana.
Plant Cell 27(3):741 (2015)
The evolutionarily conserved 8-kD protein NEDD8 (NEURAL PRECURSOR CELL EXPRESSED, DEVELOPMENTALLY DOWN-REGULATED8) belongs to the family of ubiquitin-like modifiers. Like ubiquitin, NEDD8 is conjugated to and deconjugated from target proteins. Many targets and functions of ubiquitylation have be...
Quantitative proteome profiling of human myoma and myometrium tissue reveals kinase expression signatures with potential for therapeutic intervention.
Proteomics 15(2-3):356 (2015)
Uterine leiomyomas are benign tumors affecting a large proportion of the female population. Despite the very high prevalence, the molecular basis for understanding the onset and development of the disease are still poorly understood. In this study, we profiled the proteomes and kinomes of leiomy...
De novo discovery of phenotypic intratumour heterogeneity using imaging mass spectrometry.
Journal of Pathology 235(1):3 (2015)
An essential and so far unresolved factor influencing the evolution of cancer and the clinical management of patients is intratumour clonal and phenotypic heterogeneity. However, the de novo identification of tumour subpopulations is so far both a challenging and an unresolved task. Here we pres...
Novel Flp pilus biogenesis-dependent natural transformation.
Frontiers in Microbiology 6:84 (2015)
Natural transformation has been described in bacterial species spread through nearly all major taxonomic groups. However, the current understanding of the structural components and the regulation of competence development is derived from only a few model organisms. Although natural transformatio...
Comprehensive and reproducible phosphopeptide enrichment using iron immobilized metal ion affinity chromatography (Fe-IMAC) columns.
Molecular & Cellular Proteomics 14(1):205 (2015)
Advances in phosphopeptide enrichment methods enable the identification of thousands of phosphopeptides from complex samples. Current offline enrichment approaches using TiO(2), Ti, and Fe immobilized metal ion affinity chromatography (IMAC) material in batch or microtip format are widely used, ...