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Cell Systems

Michael Reich, Thorin Tabor, Ted Liefeld, Helga Thorvaldsdóttir, Barbara Hill, Pablo Tamayo, Jill P Mesirov
Interactive analysis notebook environments promise to streamline genomics research through interleaving text, multimedia, and executable code into unified, sharable, reproducible "research narratives." However, current notebook systems require programming knowledge, limiting their wider adoption by the research community. We have developed the GenePattern Notebook environment (, to our knowledge the first system to integrate the dynamic capabilities of notebook systems with an investigator-focused, easy-to-use interface that provides access to hundreds of genomic tools without the need to write code...
August 14, 2017: Cell Systems
Ariel Feiglin, Bryce K Allen, Isaac S Kohane, Sek Won Kong
Linking putatively pathogenic variants to the tissues they affect is necessary for determining the correct diagnostic workup and therapeutic regime in undiagnosed patients. Here, we explored how gene expression across healthy tissues can be used to infer this link. We integrated 6,665 tissue-wide transcriptomes with genetic disorder knowledge bases covering 3,397 diseases. Receiver-operating characteristics (ROC) analysis using expression levels in each tissue and across tissues indicated significant but modest associations between elevated expression and phenotype for most tissues (maximum area under ROC curve = 0...
August 14, 2017: Cell Systems
Mariola Szenk, Ken A Dill, Adam M R de Graff
Bacteria and other cells show a puzzling behavior. At high growth rates, E. coli switch from respiration (which is ATP-efficient) to using fermentation for additional ATP (which is inefficient). This overflow metabolism results in a several-fold decrease in ATP produced per glucose molecule provided as food. By integrating diverse types of experimental data into a simple biophysical model, we give evidence that this onset is the result of the membrane real estate hypothesis: Fast growth drives cells to be bigger, reducing their surface-to-volume ratios...
July 25, 2017: Cell Systems
Linus J Schumacher, Philip K Maini, Ruth E Baker
Cell population heterogeneity is increasingly a focus of inquiry in biological research. For example, cell migration studies have investigated the heterogeneity of invasiveness and taxis in development, wound healing, and cancer. However, relatively little effort has been devoted to exploring when heterogeneity is mechanistically relevant and how to reliably measure it. Statistical methods from the animal movement literature offer the potential to analyze heterogeneity in collections of cell tracking data. A popular measure of heterogeneity, which we use here as an example, is the distribution of delays in directional cross-correlation...
July 25, 2017: Cell Systems
Zhengda Li, Shixuan Liu, Qiong Yang
Robust biological oscillators retain the critical ability to function in the presence of environmental perturbations. Although central architectures that support robust oscillations have been extensively studied, networks containing the same core vary drastically in their potential to oscillate, and it remains elusive what peripheral modifications to the core contribute to this functional variation. Here, we have generated a complete atlas of two- and three-node oscillators computationally, then systematically analyzed the association between network structure and robustness...
July 26, 2017: Cell Systems
Tatyana A Gubin, Hari P Iyer, Shirlene N Liew, Aartik Sarma, Alex Revelos, João Ribas, Babak Movassaghi, Zen M Chu, Ayesha N Khalid, Maulik D Majmudar, Christopher Xiang Lee
MIT Hacking Medicine is a student, academic, and community-led organization that uses systems-oriented "healthcare hacking" to address challenges around innovation in healthcare. The group has organized more than 80 events around the world that attract participants with diverse backgrounds. These participants are trained to address clinical needs from the perspective of multiple stakeholders and emphasize utility and implementation viability of proposed solutions. We describe the MIT Hacking Medicine model as a potential method to integrate collaboration and training in rapid innovation techniques into academic medical centers...
July 26, 2017: Cell Systems
Adam Conn, Ullas V Pedmale, Joanne Chory, Saket Navlakha
Transport networks serve critical functions in biological and engineered systems, and yet their design requires trade-offs between competing objectives. Due to their sessile lifestyle, plants need to optimize their architecture to efficiently acquire and distribute resources while also minimizing costs in building infrastructure. To understand how plants resolve this design trade-off, we used high-precision three-dimensional laser scanning to map the architectures of tomato, tobacco, or sorghum plants grown in several environmental conditions and through multiple developmental time points, scanning in total 505 architectures from 37 plants...
July 26, 2017: Cell Systems
Bin Lin, Bhaskar Dutta, Iain D C Fraser
A typical pathogen presents a combination of Toll-like receptor (TLR) ligands during infection. Although individual TLR pathways have been well characterized, the nature of this "combinatorial code" in pathogen sensing remains unclear. Here, we conducted a comprehensive transcriptomic analysis of primary macrophages stimulated with all possible pairwise combinations of four different TLR ligands to understand the requirements, kinetics, and outcome of combined pathway engagement. We find that signal integration between TLR pathways leads to non-additive responses for a subset of immune mediators with sustained expression (>6 hr) properties and T cell polarizing function...
July 26, 2017: Cell Systems
(no author information available yet)
This month: building bacterial organelles (Kerfeld, Tullman-Ercek), the widening scope of single cell analysis (Takebe, Glass, Rabadan), insights from yeast (Swain, Dunham), and more (Bloom, Romesberg, Gibson).
July 26, 2017: Cell Systems
Quincey Justman
No abstract text is available yet for this article.
July 26, 2017: Cell Systems
Eva Bang Harvald, Richard R Sprenger, Kathrine Brændgaard Dall, Christer S Ejsing, Ronni Nielsen, Susanne Mandrup, Alejandro Brenes Murillo, Mark Larance, Anton Gartner, Angus I Lamond, Nils J Færgeman
Starvation causes comprehensive metabolic changes, which are still not fully understood. Here, we used quantitative proteomics and RNA sequencing to examine the temporal starvation responses in wild-type Caenorhabditis elegans and animals lacking the transcription factor HLH-30. Our findings show that starvation alters the abundance of hundreds of proteins and mRNAs in a temporal manner, many of which are involved in central metabolic pathways, including lipoprotein metabolism. We demonstrate that premature death of hlh-30 animals under starvation can be prevented by knockdown of either vit-1 or vit-5, encoding two different lipoproteins...
July 26, 2017: Cell Systems
Enoch Yeung, Aaron J Dy, Kyle B Martin, Andrew H Ng, Domitilla Del Vecchio, James L Beck, James J Collins, Richard M Murray
Synthetic gene expression is highly sensitive to intragenic compositional context (promoter structure, spacing regions between promoter and coding sequences, and ribosome binding sites). However, much less is known about the effects of intergenic compositional context (spatial arrangement and orientation of entire genes on DNA) on expression levels in synthetic gene networks. We compare expression of induced genes arranged in convergent, divergent, or tandem orientations. Induction of convergent genes yielded up to 400% higher expression, greater ultrasensitivity, and dynamic range than divergent- or tandem-oriented genes...
July 26, 2017: Cell Systems
Stephen Bridgett, James Campbell, Christopher J Lord, Colm J Ryan
Genes whose function is selectively essential in the presence of cancer-associated genetic aberrations represent promising targets for the development of precision therapeutics. Here, we present CancerGD, a resource that integrates genotypic profiling with large-scale loss-of-function genetic screens in tumor cell lines to identify such genetic dependencies. CancerGD provides tools for searching, visualizing, and interpreting these genetic dependencies through the integration of functional interaction networks...
July 26, 2017: Cell Systems
Jie Tan, Georgia Doing, Kimberley A Lewis, Courtney E Price, Kathleen M Chen, Kyle C Cady, Barret Perchuk, Michael T Laub, Deborah A Hogan, Casey S Greene
Cross-experiment comparisons in public data compendia are challenged by unmatched conditions and technical noise. The ADAGE method, which performs unsupervised integration with denoising autoencoder neural networks, can identify biological patterns, but because ADAGE models, like many neural networks, are over-parameterized, different ADAGE models perform equally well. To enhance model robustness and better build signatures consistent with biological pathways, we developed an ensemble ADAGE (eADAGE) that integrated stable signatures across models...
July 26, 2017: Cell Systems
Jennifer C Fung
A model explains how a critical delay before microtubules detach from kinetochores during cell division might be achieved.
June 28, 2017: Cell Systems
Nicholas T Ingolia
Once inactive ribosomes are accounted for, ribosome footprint profiling data and pulse-labeled proteomics provide similar, accurate measurements of protein synthesis.
June 28, 2017: Cell Systems
Tony Ly, Angus I Lamond
Improved sample processing workflows enable rapid, deep analysis of human cellular and tissue proteomes.
June 28, 2017: Cell Systems
(no author information available yet)
Different biological substrates dictate design rules and enable new functions.
June 28, 2017: Cell Systems
(no author information available yet)
This month: imaging the organelle interactome (Lippincott-Schwartz), big data immunology (Pulendran, Ginhoux), protein interactomes expand (Barna, Harper, Marcotte), and computation/engineering insights (Milinkovitch, Silver, and Sastry).
June 28, 2017: Cell Systems
H Craig Mak
No abstract text is available yet for this article.
June 28, 2017: Cell Systems
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