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Cell Systems

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https://www.readbyqxmd.com/read/27889536/compact-integration-of-multi-network-topology-for-functional-analysis-of-genes
#1
Hyunghoon Cho, Bonnie Berger, Jian Peng
The topological landscape of molecular or functional interaction networks provides a rich source of information for inferring functional patterns of genes or proteins. However, a pressing yet-unsolved challenge is how to combine multiple heterogeneous networks, each having different connectivity patterns, to achieve more accurate inference. Here, we describe the Mashup framework for scalable and robust network integration. In Mashup, the diffusion in each network is first analyzed to characterize the topological context of each node...
November 22, 2016: Cell Systems
https://www.readbyqxmd.com/read/27866946/systems-genetics-approach-identifies-gene-pathways-and-adamts2-as-drivers-of-isoproterenol-induced-cardiac-hypertrophy-and-cardiomyopathy-in-mice
#2
Christoph D Rau, Milagros C Romay, Mary Tuteryan, Jessica J-C Wang, Marc Santolini, Shuxun Ren, Alain Karma, James N Weiss, Yibin Wang, Aldons J Lusis
We previously reported a genetic analysis of heart failure traits in a population of inbred mouse strains treated with isoproterenol to mimic catecholamine-driven cardiac hypertrophy. Here, we apply a co-expression network algorithm, wMICA, to perform a systems-level analysis of left ventricular transcriptomes from these mice. We describe the features of the overall network but focus on a module identified in treated hearts that is strongly related to cardiac hypertrophy and pathological remodeling. Using the causal modeling algorithm NEO, we identified the gene Adamts2 as a putative regulator of this module and validated the predictive value of NEO using small interfering RNA-mediated knockdown in neonatal rat ventricular myocytes...
November 16, 2016: Cell Systems
https://www.readbyqxmd.com/read/27866947/integrating-gwas-and-co-expression-network-data-identifies-bone-mineral-density-genes-sptbn1-and-mark3-and-an-osteoblast-functional-module
#3
Gina M Calabrese, Larry D Mesner, Joseph P Stains, Steven M Tommasini, Mark C Horowitz, Clifford J Rosen, Charles R Farber
Bone mineral density (BMD) is a highly heritable predictor of osteoporotic fracture. Genome-wide association studies (GWAS) for BMD have identified dozens of associations; yet, the genes responsible for most associations remain elusive. Here, we used a bone co-expression network to predict causal genes at BMD GWAS loci based on the premise that genes underlying a disease are often functionally related and functionally related genes are often co-expressed. By mapping genes implicated by BMD GWAS onto a bone co-expression network, we predicted and inferred the function of causal genes for 30 of 64 GWAS loci...
November 15, 2016: Cell Systems
https://www.readbyqxmd.com/read/27840078/design-and-construction-of-generalizable-rna-protein-hybrid-controllers-by-level-matched-genetic-signal-amplification
#4
Yen-Hsiang Wang, Maureen McKeague, Tammy M Hsu, Christina D Smolke
For synthetic biology applications, protein-based transcriptional genetic controllers are limited in terms of orthogonality, modularity, and portability. Although ribozyme-based switches can address these issues, their current two-stage architectures and limited dynamic range hinder their broader incorporation into systems-level genetic controllers. Here, we address these challenges by implementing an RNA-protein hybrid controller with a three-stage architecture that introduces a transcription-based amplifier between an RNA sensor and a protein actuator...
November 9, 2016: Cell Systems
https://www.readbyqxmd.com/read/27818083/shotgun-metagenomics-of-250-adult-twins-reveals-genetic-and-environmental-impacts-on-the-gut-microbiome
#5
Hailiang Xie, Ruijin Guo, Huanzi Zhong, Qiang Feng, Zhou Lan, Bingcai Qin, Kirsten J Ward, Matthew A Jackson, Yan Xia, Xu Chen, Bing Chen, Huihua Xia, Changlu Xu, Fei Li, Xun Xu, Jumana Yousuf Al-Aama, Huanming Yang, Jian Wang, Karsten Kristiansen, Jun Wang, Claire J Steves, Jordana T Bell, Junhua Li, Timothy D Spector, Huijue Jia
The gut microbiota has been typically viewed as an environmental factor for human health. Twins are well suited for investigating the concordance of their gut microbiomes and decomposing genetic and environmental influences. However, existing twin studies utilizing metagenomic shotgun sequencing have included only a few samples. Here, we sequenced fecal samples from 250 adult twins in the TwinsUK registry and constructed a comprehensive gut microbial reference gene catalog. We demonstrate heritability of many microbial taxa and functional modules in the gut microbiome, including those associated with diseases...
November 2, 2016: Cell Systems
https://www.readbyqxmd.com/read/27818082/noise-induces-the-population-level-entrainment-of-incoherent-uncoupled-intracellular-oscillators
#6
Ankit Gupta, Benjamin Hepp, Mustafa Khammash
Intracellular oscillators entrain to periodic signals by adjusting their phase and frequency. However, the low copy numbers of key molecular players make the dynamics of these oscillators intrinsically noisy, disrupting their oscillatory activity and entrainment response. Here, we use a combination of computational methods and experimental observations to reveal a functional distinction between the entrainment of individual oscillators (e.g., inside cells) and the entrainment of populations of oscillators (e...
November 2, 2016: Cell Systems
https://www.readbyqxmd.com/read/27746093/defective-signaling-in-the-jak-stat-pathway-tracks-with-chronic-inflammation-and-cardiovascular-risk-in-aging-humans
#7
Shai S Shen-Orr, David Furman, Brian A Kidd, Francois Hadad, Patricia Lovelace, Ying-Wen Huang, Yael Rosenberg-Hasson, Sally Mackey, Fatemeh A Gomari Grisar, Yishai Pickman, Holden T Maecker, Yueh-Hsiu Chien, Cornelia L Dekker, Joseph C Wu, Atul J Butte, Mark M Davis
Chronic inflammation, a decline in immune responsiveness, and reduced cardiovascular function are all associated with aging, but the relationships among these phenomena remain unclear. Here, we longitudinally profiled a total of 84 signaling conditions in 91 young and older adults and observed an age-related reduction in cytokine responsiveness within four immune cell lineages, most prominently T cells. The phenotype can be partially explained by elevated baseline levels of phosphorylated STAT (pSTAT) proteins and a different response capacity of naive versus memory T cell subsets to interleukin 6 (IL-6), interferon α (IFN-α), and, to a lesser extent, IL-21 and IFN-γ...
October 12, 2016: Cell Systems
https://www.readbyqxmd.com/read/27693023/a-single-cell-transcriptome-atlas-of-the-human-pancreas
#8
Mauro J Muraro, Gitanjali Dharmadhikari, Dominic Grün, Nathalie Groen, Tim Dielen, Erik Jansen, Leon van Gurp, Marten A Engelse, Francoise Carlotti, Eelco J P de Koning, Alexander van Oudenaarden
To understand organ function, it is important to have an inventory of its cell types and of their corresponding marker genes. This is a particularly challenging task for human tissues like the pancreas, because reliable markers are limited. Hence, transcriptome-wide studies are typically done on pooled islets of Langerhans, obscuring contributions from rare cell types and of potential subpopulations. To overcome this challenge, we developed an automated platform that uses FACS, robotics, and the CEL-Seq2 protocol to obtain the transcriptomes of thousands of single pancreatic cells from deceased organ donors, allowing in silico purification of all main pancreatic cell types...
September 29, 2016: Cell Systems
https://www.readbyqxmd.com/read/27641958/analysis-of-body-wide-unfractionated-tissue-data-to-identify-a-core-human-endothelial-transcriptome
#9
Lynn Marie Butler, Björn Mikael Hallström, Linn Fagerberg, Fredrik Pontén, Mathias Uhlén, Thomas Renné, Jacob Odeberg
Endothelial cells line blood vessels and regulate hemostasis, inflammation, and blood pressure. Proteins critical for these specialized functions tend to be predominantly expressed in endothelial cells across vascular beds. Here, we present a systems approach to identify a panel of human endothelial-enriched genes using global, body-wide transcriptomics data from 124 tissue samples from 32 organs. We identified known and unknown endothelial-enriched gene transcripts and used antibody-based profiling to confirm expression across vascular beds...
September 14, 2016: Cell Systems
https://www.readbyqxmd.com/read/27894999/matched-comparative-modeling-of-normal-and-diseased-human-airway-responses-using-a-microengineered-breathing-lung-chip
#10
Kambez H Benam, Richard Novak, Janna Nawroth, Mariko Hirano-Kobayashi, Thomas C Ferrante, Youngjae Choe, Rachelle Prantil-Baun, James C Weaver, Anthony Bahinski, Kevin K Parker, Donald E Ingber
Smoking represents a major risk factor for chronic obstructive pulmonary disease (COPD), but it is difficult to characterize smoke-induced injury responses under physiological breathing conditions in humans due to patient-to-patient variability. Here, we show that a small airway-on-a-chip device lined by living human bronchiolar epithelium from normal or COPD patients can be connected to an instrument that "breathes" whole cigarette smoke in and out of the chips to study smoke-induced pathophysiology in vitro...
November 23, 2016: Cell Systems
https://www.readbyqxmd.com/read/27894998/push-pull-and-feedback-mechanisms-can-align-signaling-system-outputs-with-inputs
#11
Steven S Andrews, William J Peria, Richard C Yu, Alejandro Colman-Lerner, Roger Brent
Many cell signaling systems, including the yeast pheromone response system, exhibit "dose-response alignment" (DoRA), in which output of one or more downstream steps closely matches the fraction of occupied receptors. DoRA can improve the fidelity of transmitted dose information. Here, we searched systematically for biochemical network topologies that produced DoRA. Most networks, including many containing feedback and feedforward loops, could not produce DoRA. However, networks including "push-pull" mechanisms, in which the active form of a signaling species stimulates downstream activity and the nominally inactive form reduces downstream activity, enabled perfect DoRA...
November 23, 2016: Cell Systems
https://www.readbyqxmd.com/read/27883892/vimentin-intermediate-filaments-template-microtubule-networks-to-enhance-persistence-in-cell-polarity-and-directed-migration
#12
Zhuo Gan, Liya Ding, Christoph J Burckhardt, Jason Lowery, Assaf Zaritsky, Karlyndsay Sitterley, Andressa Mota, Nancy Costigliola, Colby G Starker, Daniel F Voytas, Jessica Tytell, Robert D Goldman, Gaudenz Danuser
No abstract text is available yet for this article.
November 23, 2016: Cell Systems
https://www.readbyqxmd.com/read/27883891/analysis-of-cell-lineage-trees-by-exact-bayesian-inference-identifies-negative-autoregulation-of-nanog-in-mouse-embryonic-stem-cells
#13
Justin Feigelman, Stefan Ganscha, Simon Hastreiter, Michael Schwarzfischer, Adam Filipczyk, Timm Schroeder, Fabian J Theis, Carsten Marr, Manfred Claassen
Many cellular effectors of pluripotency are dynamically regulated. In principle, regulatory mechanisms can be inferred from single-cell observations of effector activity across time. However, rigorous inference techniques suitable for noisy, incomplete, and heterogeneous data are lacking. Here, we introduce stochastic inference on lineage trees (STILT), an algorithm capable of identifying stochastic models that accurately describe the quantitative behavior of cell fate markers observed using time-lapse microscopy data collected from proliferating cell populations...
November 23, 2016: Cell Systems
https://www.readbyqxmd.com/read/27883890/a-consensus-genome-scale-reconstruction-of-chinese-hamster-ovary-cell-metabolism
#14
Hooman Hefzi, Kok Siong Ang, Michael Hanscho, Aarash Bordbar, David Ruckerbauer, Meiyappan Lakshmanan, Camila A Orellana, Deniz Baycin-Hizal, Yingxiang Huang, Daniel Ley, Veronica S Martinez, Sarantos Kyriakopoulos, Natalia E Jiménez, Daniel C Zielinski, Lake-Ee Quek, Tune Wulff, Johnny Arnsdorf, Shangzhong Li, Jae Seong Lee, Giuseppe Paglia, Nicolas Loira, Philipp N Spahn, Lasse E Pedersen, Jahir M Gutierrez, Zachary A King, Anne Mathilde Lund, Harish Nagarajan, Alex Thomas, Alyaa M Abdel-Haleem, Juergen Zanghellini, Helene F Kildegaard, Bjørn G Voldborg, Ziomara P Gerdtzen, Michael J Betenbaugh, Bernhard O Palsson, Mikael R Andersen, Lars K Nielsen, Nicole Borth, Dong-Yup Lee, Nathan E Lewis
Chinese hamster ovary (CHO) cells dominate biotherapeutic protein production and are widely used in mammalian cell line engineering research. To elucidate metabolic bottlenecks in protein production and to guide cell engineering and bioprocess optimization, we reconstructed the metabolic pathways in CHO and associated them with >1,700 genes in the Cricetulus griseus genome. The genome-scale metabolic model based on this reconstruction, iCHO1766, and cell-line-specific models for CHO-K1, CHO-S, and CHO-DG44 cells provide the biochemical basis of growth and recombinant protein production...
November 23, 2016: Cell Systems
https://www.readbyqxmd.com/read/27883889/inferring-cell-state-transition-dynamics-from-lineage-trees-and-endpoint-single-cell-measurements
#15
Sahand Hormoz, Zakary S Singer, James M Linton, Yaron E Antebi, Boris I Shraiman, Michael B Elowitz
As they proliferate, living cells undergo transitions between specific molecularly and developmentally distinct states. Despite the functional centrality of these transitions in multicellular organisms, it has remained challenging to determine which transitions occur and at what rates without perturbations and cell engineering. Here, we introduce kin correlation analysis (KCA) and show that quantitative cell-state transition dynamics can be inferred, without direct observation, from the clustering of cell states on pedigrees (lineage trees)...
November 23, 2016: Cell Systems
https://www.readbyqxmd.com/read/27883888/personalized-disease-models-on-a-chip
#16
Nalin Tejavibulya, Samuel K Sia
Organs-on-chips are beginning to serve as a useful platform for individualized disease models in a way that minimizes patient-to-patient variability.
November 23, 2016: Cell Systems
https://www.readbyqxmd.com/read/27883887/signaling-tug-of-war-delivers-the-whole-message
#17
Andrea Y Weiße, Ahmad A Mannan, Diego A Oyarzún
How do cells transmit biochemical signals accurately? It turns out, pushing and pulling can go a long way.
November 23, 2016: Cell Systems
https://www.readbyqxmd.com/read/27883886/cho-cells-can-make-more-protein
#18
Sarah W Harcum, Kelvin H Lee
A new comprehensive genome-scale metabolic model of Chinese hamster ovary cells identifies pathways for improving biopharmaceutical protein production.
November 23, 2016: Cell Systems
https://www.readbyqxmd.com/read/27883885/commendation-for-exposing-key-advantage-of-organ-chip-approach
#19
LETTER
Kambez H Benam, Donald E Ingber
No abstract text is available yet for this article.
November 23, 2016: Cell Systems
https://www.readbyqxmd.com/read/27883884/principles-of-systems-biology-no-11
#20
(no author information available yet)
This month: AI that learns patterns and facts, new protein-RNA and protein-protein relationships, engineering signaling and metabolism, and more variants of Cas9.
November 23, 2016: Cell Systems
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