Single-cell polyadenylation site mapping reveals 3' isoform choice variability
Cell-to-cell variability in gene expression is important for many processes in biology, including embryonic development and stem cell homeostasis. While heterogeneity of gene expression levels has been extensively studied, less attention has been paid to mRNA polyadenylation isoform choice. 3' untranslated regions regulate mRNA fate, and their choice is tightly controlled during development, but how 3' isoform usage varies within genetically and developmentally homogeneous cell populations has not been explored. Here, we perform genome-wide quantification of polyadenylation site usage in single mouse embryonic and neural s...
Source: Molecular Systems Biology - June 3, 2015 Category: Molecular Biology Authors: Velten, L., Anders, S., Pekowska, A., Jarvelin, A. I., Huber, W., Pelechano, V., Steinmetz, L. M. Tags: Chromatin, Epigenetics, Genomics & Functional Genomics, Computational Biology, Methods & Resources Articles Source Type: research
Systems-wide analysis of BCR signalosomes and downstream phosphorylation and ubiquitylation
B-cell receptor (BCR) signaling is essential for the development and function of B cells; however, the spectrum of proteins involved in BCR signaling is not fully known. Here we used quantitative mass spectrometry-based proteomics to monitor the dynamics of BCR signaling complexes (signalosomes) and to investigate the dynamics of downstream phosphorylation and ubiquitylation signaling. We identify most of the previously known components of BCR signaling, as well as many proteins that have not yet been implicated in this system. BCR activation leads to rapid tyrosine phosphorylation and ubiquitylation of the receptor-proxim...
Source: Molecular Systems Biology - June 2, 2015 Category: Molecular Biology Authors: Satpathy, S., Wagner, S. A., Beli, P., Gupta, R., Kristiansen, T. A., Malinova, D., Francavilla, C., Tolar, P., Bishop, G. A., Hostager, B. S., Choudhary, C. Tags: Post-translational Modifications, Proteolysis & Proteomics, Signal Transduction Articles Source Type: research
The making of Tara Oceans: funding blue skies research for our Blue Planet
(Source: Molecular Systems Biology)
Source: Molecular Systems Biology - May 21, 2015 Category: Molecular Biology Authors: Karsenti, E. Tags: Genome-Scale & Integrative Biology Editorials Source Type: research
Computational eco-systems biology in Tara Oceans: translating data into knowledge
(Source: Molecular Systems Biology)
Source: Molecular Systems Biology - May 21, 2015 Category: Molecular Biology Authors: Sunagawa, S., Karsenti, E., Bowler, C., Bork, P. Tags: Computational Biology, Genome-Scale & Integrative Biology, Microbiology, Virology & Host Pathogen Interaction Editorials Source Type: research
Genome-wide study of mRNA degradation and transcript elongation in Escherichia coli
(Source: Molecular Systems Biology)
Source: Molecular Systems Biology - May 11, 2015 Category: Molecular Biology Authors: Chen, H., Shiroguchi, K., Ge, H., Xie, X. S. Tags: Corrigendum Source Type: research
Fractional killing arises from cell-to-cell variability in overcoming a caspase activity threshold
When cells are exposed to death ligands such as TRAIL, a fraction undergoes apoptosis and a fraction survives; if surviving cells are re-exposed to TRAIL, fractional killing is once again observed. Therapeutic antibodies directed against TRAIL receptors also cause fractional killing, even at saturating concentrations, limiting their effectiveness. Fractional killing arises from cell-to-cell fluctuations in protein levels (extrinsic noise), but how this results in a clean bifurcation between life and death remains unclear. In this paper, we identify a threshold in the rate and timing of initiator caspase activation that dis...
Source: Molecular Systems Biology - May 7, 2015 Category: Molecular Biology Authors: Roux, J., Hafner, M., Bandara, S., Sims, J. J., Hudson, H., Chai, D., Sorger, P. K. Tags: Autophagy & Cell Death, Quantitative Biology & Dynamical Systems, Signal Transduction Articles Source Type: research
Orthogonal control of expression mean and variance by epigenetic features at different genomic loci
While gene expression noise has been shown to drive dramatic phenotypic variations, the molecular basis for this variability in mammalian systems is not well understood. Gene expression has been shown to be regulated by promoter architecture and the associated chromatin environment. However, the exact contribution of these two factors in regulating expression noise has not been explored. Using a dual-reporter lentiviral model system, we deconvolved the influence of the promoter sequence to systematically study the contribution of the chromatin environment at different genomic locations in regulating expression noise. By in...
Source: Molecular Systems Biology - May 5, 2015 Category: Molecular Biology Authors: Dey, S. S., Foley, J. E., Limsirichai, P., Schaffer, D. V., Arkin, A. P. Tags: Chromatin, Epigenetics, Genomics & Functional Genomics, Quantitative Biology & Dynamical Systems, Transcription Articles Source Type: research
Tuning noise in gene expression
The relative contribution of promoter architecture and the associated chromatin environment in regulating gene expression noise has remained elusive. In their recent work, Arkin, Schaffer and colleagues (Dey et al, 2015) show that mean expression and noise for a given promoter at different genomic loci are uncorrelated and influenced by the local chromatin environment. (Source: Molecular Systems Biology)
Source: Molecular Systems Biology - May 5, 2015 Category: Molecular Biology Authors: Tyagi, S. Tags: Chromatin, Epigenetics, Genomics & Functional Genomics, Quantitative Biology & Dynamical Systems, Transcription News [amp ] Views Source Type: research
Systematic discovery of drug interaction mechanisms
Drug combinations are increasingly important in disease treatments, for combating drug resistance, and for elucidating fundamental relationships in cell physiology. When drugs are combined, their individual effects on cells may be amplified or weakened. Such drug interactions are crucial for treatment efficacy, but their underlying mechanisms remain largely unknown. To uncover the causes of drug interactions, we developed a systematic approach based on precise quantification of the individual and joint effects of antibiotics on growth of genome-wide Escherichia coli gene deletion strains. We found that drug interactions be...
Source: Molecular Systems Biology - April 29, 2015 Category: Molecular Biology Authors: Chevereau, G., Bollenbach, T. Tags: Pharmacology & Drug Discovery, Quantitative Biology & Dynamical Systems Reports Source Type: research
Using light to shape chemical gradients for parallel and automated analysis of chemotaxis
Numerous molecular components have been identified that regulate the directed migration of eukaryotic cells toward sources of chemoattractant. However, how the components of this system are wired together to coordinate multiple aspects of the response, such as directionality, speed, and sensitivity to stimulus, remains poorly understood. Here we developed a method to shape chemoattractant gradients optically and analyze cellular chemotaxis responses of hundreds of living cells per well in 96-well format by measuring speed changes and directional accuracy. We then systematically characterized migration and chemotaxis phenot...
Source: Molecular Systems Biology - April 23, 2015 Category: Molecular Biology Authors: Collins, S. R., Yang, H. W., Bonger, K. M., Guignet, E. G., Wandless, T. J., Meyer, T. Tags: Methods & Resources, Signal Transduction Articles Source Type: research
Inferring causal metabolic signals that regulate the dynamic TORC1-dependent transcriptome
Cells react to nutritional cues in changing environments via the integrated action of signaling, transcriptional, and metabolic networks. Mechanistic insight into signaling processes is often complicated because ubiquitous feedback loops obscure causal relationships. Consequently, the endogenous inputs of many nutrient signaling pathways remain unknown. Recent advances for system-wide experimental data generation have facilitated the quantification of signaling systems, but the integration of multi-level dynamic data remains challenging. Here, we co-designed dynamic experiments and a probabilistic, model-based method to in...
Source: Molecular Systems Biology - April 17, 2015 Category: Molecular Biology Authors: Oliveira, A. P., Dimopoulos, S., Busetto, A. G., Christen, S., Dechant, R., Falter, L., Haghir Chehreghani, M., Jozefczuk, S., Ludwig, C., Rudroff, F., Schulz, J. C., Gonzalez, A., Soulard, A., Stracka, D., Aebersold, R., Buhmann, J. M., Hall, M. N., Pete Tags: Genome-Scale & Integrative Biology, Metabolism Articles Source Type: research
Differential genetic interactions of yeast stress response MAPK pathways
In this study, we have performed a large-scale genetic interaction analysis in Saccharomyces cerevisiae involving approximately 49 x 1,200 double mutants in the presence of five different stress conditions, including osmotic, oxidative and cell wall-altering stresses. This resulted in the generation of a differential E-MAP (or dE-MAP) comprising over 250,000 measurements of conditional interactions. We found an extensive number of conditional genetic interactions that recapitulate known stress-specific functional associations. Furthermore, we have also uncovered previously unrecognized roles involving the phospha...
Source: Molecular Systems Biology - April 17, 2015 Category: Molecular Biology Authors: Martin, H., Shales, M., Fernandez-Pinar, P., Wei, P., Molina, M., Fiedler, D., Shokat, K. M., Beltrao, P., Lim, W., Krogan, N. J. Tags: Chromatin, Epigenetics, Genomics & Functional Genomics, Network Biology Articles Source Type: research
Integrative network analysis reveals molecular mechanisms of blood pressure regulation
Genome-wide association studies (GWAS) have identified numerous loci associated with blood pressure (BP). The molecular mechanisms underlying BP regulation, however, remain unclear. We investigated BP-associated molecular mechanisms by integrating BP GWAS with whole blood mRNA expression profiles in 3,679 individuals, using network approaches. BP transcriptomic signatures at the single-gene and the coexpression network module levels were identified. Four coexpression modules were identified as potentially causal based on genetic inference because expression-related SNPs for their corresponding genes demonstrated enrichment...
Source: Molecular Systems Biology - April 16, 2015 Category: Molecular Biology Authors: Huan, T., Meng, Q., Saleh, M. A., Norlander, A. E., Joehanes, R., Zhu, J., Chen, B. H., Zhang, B., Johnson, A. D., Ying, S., Courchesne, P., Raghavachari, N., Wang, R., Liu, P., The International Consortium for Blood Pressure GWAS (ICBP), O'Donnell, C. J. Tags: Genome-Scale & Integrative Biology, Molecular Biology of Disease Articles Source Type: research
A growth-rate composition formula for the growth of E. coli on co-utilized carbon substrates
When bacteria are cultured in medium with multiple carbon substrates, they frequently consume these substrates simultaneously. Building on recent advances in the understanding of metabolic coordination exhibited by Escherichia coli cells through cAMP-Crp signaling, we show that this signaling system responds to the total carbon-uptake flux when substrates are co-utilized and derive a mathematical formula that accurately predicts the resulting growth rate, based only on the growth rates on individual substrates. (Source: Molecular Systems Biology)
Source: Molecular Systems Biology - April 9, 2015 Category: Molecular Biology Authors: Hermsen, R., Okano, H., You, C., Werner, N., Hwa, T. Tags: Metabolism, Quantitative Biology & Dynamical Systems Reports Source Type: research
Kinase-two-hybrid: towards the conditional interactome
The dynamics of the protein–protein interaction network and how it responds to biological perturbations remain difficult to assay by most traditional techniques. A novel kinase-dependent yeast two-hybrid framework by Stelzl and colleagues (Grossmann et al, 2015) provides a new prism to study how tyrosine phosphorylation regulates the changes in the interactome under varying conditions. (Source: Molecular Systems Biology)
Source: Molecular Systems Biology - March 26, 2015 Category: Molecular Biology Authors: Ochoa, D., Beltrao, P. Tags: Network Biology, Post-translational Modifications, Proteolysis & Proteomics News [amp ] Views Source Type: research
