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Cell Systems

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https://www.readbyqxmd.com/read/28647475/advanced-cell-classifier-user-friendly-machine-learning-based-software-for-discovering-phenotypes-in-high-content-imaging-data
#1
Filippo Piccinini, Tamas Balassa, Abel Szkalisity, Csaba Molnar, Lassi Paavolainen, Kaisa Kujala, Krisztina Buzas, Marie Sarazova, Vilja Pietiainen, Ulrike Kutay, Kevin Smith, Peter Horvath
High-content, imaging-based screens now routinely generate data on a scale that precludes manual verification and interrogation. Software applying machine learning has become an essential tool to automate analysis, but these methods require annotated examples to learn from. Efficiently exploring large datasets to find relevant examples remains a challenging bottleneck. Here, we present Advanced Cell Classifier (ACC), a graphical software package for phenotypic analysis that addresses these difficulties. ACC applies machine-learning and image-analysis methods to high-content data generated by large-scale, cell-based experiments...
June 16, 2017: Cell Systems
https://www.readbyqxmd.com/read/28624614/gene-transfer-agent-promotes-evolvability-within-the-fittest-subpopulation-of-a-bacterial-pathogen
#2
Maxime Québatte, Matthias Christen, Alexander Harms, Jonas Körner, Beat Christen, Christoph Dehio
The Bartonella gene transfer agent (BaGTA) is an archetypical example for domestication of a phage-derived element to permit high-frequency genetic exchange in bacterial populations. Here we used multiplexed transposon sequencing (TnSeq) and single-cell reporters to globally define the core components and transfer dynamics of BaGTA. Our systems-level analysis has identified inner- and outer-circle components of the BaGTA system, including 55 regulatory components, as well as an additional 74 and 107 components mediating donor transfer and recipient uptake functions...
June 14, 2017: Cell Systems
https://www.readbyqxmd.com/read/28624615/cell-size-dependent-transcription-of-flc-and-its-antisense-long-non-coding-rna-coolair-explain-cell-to-cell-expression-variation
#3
Robert Ietswaart, Stefanie Rosa, Zhe Wu, Caroline Dean, Martin Howard
Single-cell quantification of transcription kinetics and variability promotes a mechanistic understanding of gene regulation. Here, using single-molecule RNA fluorescence in situ hybridization and mathematical modeling, we dissect cellular RNA dynamics for Arabidopsis FLOWERING LOCUS C (FLC). FLC expression quantitatively determines flowering time and is regulated by antisense (COOLAIR) transcription. In cells without observable COOLAIR expression, we quantify FLC transcription initiation, elongation, intron processing, and lariat degradation, as well as mRNA release from the locus and degradation...
June 8, 2017: Cell Systems
https://www.readbyqxmd.com/read/28601560/stochastic-modeling-yields-a-mechanistic-framework-for-spindle-attachment-error-correction-in-budding-yeast-mitosis
#4
Emily S Tubman, Sue Biggins, David J Odde
Proper segregation of the replicated genome requires that kinetochores form and maintain bioriented, amphitelic attachments to microtubules from opposite spindle poles and eliminate erroneous, syntelic attachments to microtubules from the same spindle pole. Phosphorylation of kinetochore proteins destabilizes low-tension kinetochore-microtubule attachments, yet tension stabilizes bioriented attachments. This conundrum for forming high-tension amphitelic attachments is recognized as the "initiation problem of biorientation (IPBO)...
June 6, 2017: Cell Systems
https://www.readbyqxmd.com/read/28601559/an-optimized-shotgun-strategy-for-the-rapid-generation-of-comprehensive-human-proteomes
#5
Dorte B Bekker-Jensen, Christian D Kelstrup, Tanveer S Batth, Sara C Larsen, Christa Haldrup, Jesper B Bramsen, Karina D Sørensen, Søren Høyer, Torben F Ørntoft, Claus L Andersen, Michael L Nielsen, Jesper V Olsen
This study investigates the challenge of comprehensively cataloging the complete human proteome from a single-cell type using mass spectrometry (MS)-based shotgun proteomics. We modify a classical two-dimensional high-resolution reversed-phase peptide fractionation scheme and optimize a protocol that provides sufficient peak capacity to saturate the sequencing speed of modern MS instruments. This strategy enables the deepest proteome of a human single-cell type to date, with the HeLa proteome sequenced to a depth of ∼584,000 unique peptide sequences and ∼14,200 protein isoforms (∼12,200 protein-coding genes)...
June 6, 2017: Cell Systems
https://www.readbyqxmd.com/read/28601558/systematic-quantification-of-population-cell-death-kinetics-in-mammalian-cells
#6
Giovanni C Forcina, Megan Conlon, Alex Wells, Jennifer Yinuo Cao, Scott J Dixon
Cytotoxic compounds are important drugs and research tools. Here, we introduce a method, scalable time-lapse analysis of cell death kinetics (STACK), to quantify the kinetics of compound-induced cell death in mammalian cells at the population level. STACK uses live and dead cell markers, high-throughput time-lapse imaging, and mathematical modeling to determine the kinetics of population cell death over time. We used STACK to profile the effects of over 1,800 bioactive compounds on cell death in two human cancer cell lines, resulting in a large and freely available dataset...
June 5, 2017: Cell Systems
https://www.readbyqxmd.com/read/28578850/time-resolved-proteomics-extends-ribosome-profiling-based-measurements-of-protein-synthesis-dynamics
#7
Tzu-Yu Liu, Hector H Huang, Diamond Wheeler, Yichen Xu, James A Wells, Yun S Song, Arun P Wiita
Ribosome profiling is a widespread tool for studying translational dynamics in human cells. Its central assumption is that ribosome footprint density on a transcript quantitatively reflects protein synthesis. Here, we test this assumption using pulsed-SILAC (pSILAC) high-accuracy targeted proteomics. We focus on multiple myeloma cells exposed to bortezomib, a first-line chemotherapy and proteasome inhibitor. In the absence of drug effects, we found that direct measurement of protein synthesis by pSILAC correlated well with indirect measurement of synthesis from ribosome footprint density...
May 26, 2017: Cell Systems
https://www.readbyqxmd.com/read/28544883/the-limiting-pool-mechanism-fails-to-control-the-size-of-multiple-organelles
#8
Lishibanya Mohapatra, Thibaut J Lagny, David Harbage, Predrag R Jelenkovic, Jane Kondev
How the size of micrometer-scale cellular structures such as the mitotic spindle, cytoskeletal filaments, the nucleus, the nucleolus, and other non-membrane bound organelles is controlled despite a constant turnover of their constituent parts is a central problem in biology. Experiments have implicated the limiting-pool mechanism: structures grow by stochastic addition of molecular subunits from a finite pool until the rates of subunit addition and removal are balanced, producing a structure of well-defined size...
May 24, 2017: Cell Systems
https://www.readbyqxmd.com/read/28544882/inference-and-evolutionary-analysis-of-genome-scale-regulatory-networks-in-large-phylogenies
#9
Christopher Koch, Jay Konieczka, Toni Delorey, Ana Lyons, Amanda Socha, Kathleen Davis, Sara A Knaack, Dawn Thompson, Erin K O'Shea, Aviv Regev, Sushmita Roy
Changes in transcriptional regulatory networks can significantly contribute to species evolution and adaptation. However, identification of genome-scale regulatory networks is an open challenge, especially in non-model organisms. Here, we introduce multi-species regulatory network learning (MRTLE), a computational approach that uses phylogenetic structure, sequence-specific motifs, and transcriptomic data, to infer the regulatory networks in different species. Using simulated data from known networks and transcriptomic data from six divergent yeasts, we demonstrate that MRTLE predicts networks with greater accuracy than existing methods because it incorporates phylogenetic information...
May 24, 2017: Cell Systems
https://www.readbyqxmd.com/read/28544881/mammalian-systems-biotechnology-reveals-global-cellular-adaptations-in-a-recombinant-cho-cell-line
#10
Faraaz Noor Khan Yusufi, Meiyappan Lakshmanan, Ying Swan Ho, Bernard Liat Wen Loo, Pramila Ariyaratne, Yuansheng Yang, Say Kong Ng, Tessa Rui Min Tan, Hock Chuan Yeo, Hsueh Lee Lim, Sze Wai Ng, Ai Ping Hiu, Chung Ping Chow, Corrine Wan, Shuwen Chen, Gavin Teo, Gao Song, Ju Xin Chin, Xiaoan Ruan, Ken Wing Kin Sung, Wei-Shou Hu, Miranda Gek Sim Yap, Muriel Bardor, Niranjan Nagarajan, Dong-Yup Lee
Effective development of host cells for therapeutic protein production is hampered by the poor characterization of cellular transfection. Here, we employed a multi-omics-based systems biotechnology approach to elucidate the genotypic and phenotypic differences between a wild-type and recombinant antibody-producing Chinese hamster ovary (CHO) cell line. At the genomic level, we observed extensive rearrangements in specific targeted loci linked to transgene integration sites. Transcriptional re-wiring of DNA damage repair and cellular metabolism in the antibody producer, via changes in gene copy numbers, was also detected...
May 24, 2017: Cell Systems
https://www.readbyqxmd.com/read/28544880/systems-wide-studies-uncover-commander-a-multiprotein-complex-essential-to-human-development
#11
REVIEW
Anna L Mallam, Edward M Marcotte
Recent mass spectrometry maps of the human interactome independently support the existence of a large multiprotein complex, dubbed "Commander." Broadly conserved across animals and ubiquitously expressed in nearly every human cell type examined thus far, Commander likely plays a fundamental cellular function, akin to other ubiquitous machines involved in expression, proteostasis, and trafficking. Experiments on individual subunits support roles in endosomal protein sorting, including the trafficking of Notch proteins, copper transporters, and lipoprotein receptors...
May 24, 2017: Cell Systems
https://www.readbyqxmd.com/read/28544879/when-is-enough-enough
#12
Cristian Suarez, Patrick M McCall, Margaret L Gardel, David R Kovar
Computational simulations of polymerizing actin filaments indicate that competition for a limiting pool of building blocks is not sufficient to control their length.
May 24, 2017: Cell Systems
https://www.readbyqxmd.com/read/28544878/evolutionary-context-improves-regulatory-network-predictions
#13
Jonathan L Gordon, Brigida Gallone, Steven Maere, Kevin J Verstrepen
A novel algorithm harnesses phylogenetic information and facilitates a better understanding of the evolutionary divergence of gene regulation between species.
May 24, 2017: Cell Systems
https://www.readbyqxmd.com/read/28544877/what-is-the-role-of-circuit-design-in-the-advancement-of-synthetic-biology-part-2
#14
(no author information available yet)
Embracing the constraints and principles of variation, environment, evolution, and ecology.
May 24, 2017: Cell Systems
https://www.readbyqxmd.com/read/28544876/principles-of-systems-biology-no-17
#15
(no author information available yet)
This month: understanding spatial arrangements (Süel/Laue/Schweisguth/de Lorenzo), a giant virus sheds light on evolution (Koonin), synthetic systems (Comtet, Wang, Pósfai), and omics tools (Siuzdak, Kim).
May 24, 2017: Cell Systems
https://www.readbyqxmd.com/read/28544875/interpretation-as-the-new-distribution
#16
EDITORIAL
H Craig Mak
No abstract text is available yet for this article.
May 24, 2017: Cell Systems
https://www.readbyqxmd.com/read/28527885/maintenance-of-atp-homeostasis-triggers-metabolic-shifts-in-gas-fermenting-acetogens
#17
Kaspar Valgepea, Renato de Souza Pinto Lemgruber, Kieran Meaghan, Robin William Palfreyman, Tanus Abdalla, Björn Daniel Heijstra, James Bruce Behrendorff, Ryan Tappel, Michael Köpke, Séan Dennis Simpson, Lars Keld Nielsen, Esteban Marcellin
Acetogens are promising cell factories for producing fuels and chemicals from waste feedstocks via gas fermentation, but quantitative characterization of carbon, energy, and redox metabolism is required to guide their rational metabolic engineering. Here, we explore acetogen gas fermentation using physiological, metabolomics, and transcriptomics data for Clostridium autoethanogenum steady-state chemostat cultures grown on syngas at various gas-liquid mass transfer rates. We observe that C. autoethanogenum shifts from acetate to ethanol production to maintain ATP homeostasis at higher biomass concentrations but reaches a limit at a molar acetate/ethanol ratio of ∼1...
May 24, 2017: Cell Systems
https://www.readbyqxmd.com/read/28501650/prober-provides-a-general-toolkit-for-analyzing-sequencing-based-toeprinting-assays
#18
Bo Li, Akshay Tambe, Sharon Aviran, Lior Pachter
A number of sequencing-based transcriptase drop-off assays have recently been developed to probe post-transcriptional dynamics of RNA-protein interaction, RNA structure, and RNA modification. Although these assays survey a diverse set of epitranscriptomic marks, we use the term toeprinting assays since they share methodological similarities. Their interpretation is predicated on addressing a similar computational challenge: how to learn isoform-specific chemical modification profiles in the face of complex read multi-mapping...
May 24, 2017: Cell Systems
https://www.readbyqxmd.com/read/28365151/a-cell-surface-membrane-protein-signature-for-glioblastoma
#19
Dhimankrishna Ghosh, Cory C Funk, Juan Caballero, Nameeta Shah, Katherine Rouleau, John C Earls, Liliana Soroceanu, Greg Foltz, Charles S Cobbs, Nathan D Price, Leroy Hood
We present a systems strategy that facilitated the development of a molecular signature for glioblastoma (GBM), composed of 33 cell-surface transmembrane proteins. This molecular signature, GBMSig, was developed through the integration of cell-surface proteomics and transcriptomics from patient tumors in the REMBRANDT (n = 228) and TCGA datasets (n = 547) and can separate GBM patients from control individuals with a Matthew's correlation coefficient value of 0.87 in a lock-down test. Functionally, 17/33 GBMSig proteins are associated with transforming growth factor β signaling pathways, including CD47, SLC16A1, HMOX1, and MRC2...
May 24, 2017: Cell Systems
https://www.readbyqxmd.com/read/28365149/absolute-quantification-of-protein-and-mrna-abundances-demonstrate-variability-in-gene-specific-translation-efficiency-in-yeast
#20
Petri-Jaan Lahtvee, Benjamín J Sánchez, Agata Smialowska, Sergo Kasvandik, Ibrahim E Elsemman, Francesco Gatto, Jens Nielsen
Protein synthesis is the most energy-consuming process in a proliferating cell, and understanding what controls protein abundances represents a key question in biology and biotechnology. We quantified absolute abundances of 5,354 mRNAs and 2,198 proteins in Saccharomyces cerevisiae under ten environmental conditions and protein turnover for 1,384 proteins under a reference condition. The overall correlation between mRNA and protein abundances across all conditions was low (0.46), but for differentially expressed proteins (n = 202), the median mRNA-protein correlation was 0...
May 24, 2017: Cell Systems
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