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Current Opinion in Systems Biology

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https://www.readbyqxmd.com/read/29725624/organizing-biochemistry-in-space-and-time-using-prion-like-self-assembly
#1
Christopher M Jakobson, Daniel F Jarosz
Prion-like proteins have the capacity to adopt multiple stable conformations, at least one of which can recruit proteins from the native conformation into the alternative fold. Although classically associated with disease, prion-like assembly has recently been proposed to organize a range of normal biochemical processes in space and time. Organisms from bacteria to mammals use prion-like mechanisms to (re)organize their proteome in response to intracellular and extracellular stimuli. Prion-like behavior is an economical means to control biochemistry and gene regulation at the systems level, and prions can act as protein-based genes to facilitate quasi-Lamarckian inheritance of induced traits...
April 2018: Current Opinion in Systems Biology
https://www.readbyqxmd.com/read/29623300/identifying-noise-sources-governing-cell-to-cell-variability
#2
Simon Mitchell, Alexander Hoffmann
Phenotypic differences often occur even in clonal cell populations. Many potential sources of such variation have been identified, from biophysical rate variance intrinsic to all chemical processes to asymmetric division of molecular components extrinsic to any particular signaling pathway. Identifying the sources of phenotypic variation and quantifying their contributions to cell fate variation is not possible without accurate single cell data. By combining such data with mathematical models of potential noise sources it is possible to characterize the impact of varying levels of each noise source and identify which sources of variation best explain the experimental observations...
April 2018: Current Opinion in Systems Biology
https://www.readbyqxmd.com/read/29552673/the-paths-of-mortality-how-understanding-the-biology-of-aging-can-help-explain-systems-behavior-of-single-cells
#3
Matthew M Crane, Matt Kaeberlein
Aging is a fundamental aspect of life, yet also one of the most confounding. In individual cells, aging results in a progressive decline which affects all organelles and reduces a cell's ability to maintain homeostasis. Because of the interconnected nature of cellular systems, the failure of even a single organelle can have cascading effects. We are just beginning to understand the dramatic physiological changes that occur during aging. Because most aging research has focused on population dynamics, or differences between wild-type and mutant populations, single-cell behavior has been largely overlooked...
April 2018: Current Opinion in Systems Biology
https://www.readbyqxmd.com/read/29552672/single-cell-systems-biology-probing-the-basic-unit-of-information-flow
#4
Simona Patange, Michelle Girvan, Daniel R Larson
Gene expression varies across cells in a population or a tissue. This heterogeneity has come into sharp focus in recent years through developments in new imaging and sequencing technologies. However, our ability to measure variation has outpaced our ability to interpret it. Much of the variability may arise from random effects occurring in the processes of gene expression (transcription, RNA processing and decay, translation). The molecular basis of these effects is largely unknown. Likewise, a functional role of this variability in growth, differentiation and disease has only been elucidated in a few cases...
April 2018: Current Opinion in Systems Biology
https://www.readbyqxmd.com/read/29308439/robustness-accuracy-and-cell-state-heterogeneity-in-biological-systems
#5
Roy Wollman
The robustness of biological systems is often depicted as a key system-level emergent property that allows uniform phenotypes in fluctuating environments. Yet, analysis of single-cell signaling responses identified multiple examples of cellular responses with high degrees of heterogeneity. Here we discuss the implications of the observed lack of response accuracy in the context of new observations coming from single-cell approaches. Single-cell approaches provide a new way to measure the abundance of thousands of molecular species in a single-cell...
April 2018: Current Opinion in Systems Biology
https://www.readbyqxmd.com/read/29104947/improvements-in-protein-production-in-mammalian-cells-from-targeted-metabolic-engineering
#6
Anne Richelle, Nathan E Lewis
Bioprocess optimization has yielded powerful clones for biotherapeutic production. However, new genomic technologies allow more targeted approaches to cell line development. Here we review efforts to enhance protein production in mammalian cells through metabolic engineering. Most efforts aimed to reduce toxic byproducts accumulation to enhance protein productivity. However, recent work highlights the possibility of regulating other desirable traits (e.g., apoptosis and glycosylation) by targeting central metabolism since these processes are interconnected...
December 2017: Current Opinion in Systems Biology
https://www.readbyqxmd.com/read/29062976/recent-progress-and-open-challenges-in-modeling-p53-dynamics-in-single-cells
#7
Eric Batchelor, Alexander Loewer
In mammalian cells, the tumor suppressor p53 is activated upon a variety of cellular stresses and ensures an appropriate response ranging from arrest and repair to the induction of senescence and apoptosis. Quantitative measurements in individual living cells showed stimulus-dependent dynamics of p53 accumulation upon stress induction. Due to the complexity of the underlying biochemical interactions, mathematical models were indispensable for understanding the topology of the network regulating p53 dynamics...
June 2017: Current Opinion in Systems Biology
https://www.readbyqxmd.com/read/29057378/systems-biology-in-the-central-nervous-system-a-brief-perspective-on-essential-recent-advancements
#8
Joseph D Dougherty, Chengran Yang, Allison M Lake
As recent advances in human genetics have begun to more rapidly identify the individual genes contributing to risk of psychiatric disease, the spotlight now turns to understanding how disruption of these genes alters the brain, and thus behavior. Compared to other tissues, cellular complexity in the brain provides both a substantial challenge and a significant opportunity for systems biology approaches. Current methods are maturing that will allow for finally defining the 'parts list' for the functioning mouse and human brains, enabling new approaches to defining how the system goes awry in disorders of the CNS...
June 2017: Current Opinion in Systems Biology
https://www.readbyqxmd.com/read/29057377/cellular-network-perturbations-by-disease-associated-variants
#9
Jared A Sewell, Juan I Fuxman Bass
Genetic and genome-wide association studies (GWAS) have identified a myriad of human disease-associated genomic variants. However, these studies do not reveal the mechanisms by which these variants perturb cellular networks, a necessary step to intervene and improve disease outcomes. This has been challenging because multiple variants are present in haplotype blocks, thereby confounding the identification of causal variants, and because most reside in noncoding regions. Here, we review recent advances in the identification of functional variants and gene-variant associations...
June 2017: Current Opinion in Systems Biology
https://www.readbyqxmd.com/read/29038793/mechanisms-of-cell-polarization
#10
Wouter-Jan Rappel, Leah Edelstein-Keshet
Cell polarization is a key step in the migration, development, and organization of eukaryotic cells, both at the single cell and multicellular level. Research on the mechanisms that give rise to polarization of a given cell, and organization of polarity within a tissue has led to new understanding across cellular and developmental biology. In this review, we describe some of the history of theoretical and experimental aspects of the field, as well as some interesting questions and challenges for the future.
June 2017: Current Opinion in Systems Biology
https://www.readbyqxmd.com/read/28695216/from-perception-to-action-in-songbird-production-dynamics-of-a-whole-loop
#11
Ana Amador, Santiago Boari, Gabriel B Mindlin
Birdsong emerges when a set of highly interconnected brain areas manage to generate a complex output. This consists of precise respiratory rhythms as well as motor instructions to control the vocal organ configuration. In this way, during birdsong production, dedicated cortical areas interact with life-supporting ones in the brainstem, such as the respiratory nuclei. We discuss an integrative view of this interaction together with a widely accepted "top-down" representation of the song system. We also show that a description of this neural network in terms of dynamical systems allows to explore songbird production and processing by generating testable predictions...
June 2017: Current Opinion in Systems Biology
https://www.readbyqxmd.com/read/29082337/inference-of-cell-type-specific-regulatory-networks-on-mammalian-lineages
#12
Deborah Chasman, Sushmita Roy
Transcriptional regulatory networks are at the core of establishing cell type specific gene expression programs. In mammalian systems, such regulatory networks are determined by multiple levels of regulation, including by transcription factors, chromatin environment, and three-dimensional organization of the genome. Recent efforts to measure diverse regulatory genomic datasets across multiple cell types and tissues offer unprecedented opportunities to examine the context-specificity and dynamics of regulatory networks at a greater resolution and scale than before...
April 2017: Current Opinion in Systems Biology
https://www.readbyqxmd.com/read/29082336/genome-variation-across-cancers-scales-with-tissue-stiffness-an-invasion-mutation-mechanism-and-implications-for-immune-cell-infiltration
#13
Charlotte R Pfeifer, Cory M Alvey, Jerome Irianto, Dennis E Discher
Many different types of soft and solid tumors have now been sequenced, and meta-analyses suggest that genomic variation across tumors scales with the stiffness of the tumors' tissues of origin. The opinion expressed here is based on a review of current genomics data, and it considers multiple 'mechanogenomics' mechanisms to potentially explain this scaling of mutation rate with tissue stiffness. Since stiff solid tissues have higher density of fibrous collagen matrix, which should decrease tissue porosity, cancer cell proliferation could be affected and so could invasion into stiff tissues as the nucleus is squeezed sufficiently to enhance DNA damage...
April 2017: Current Opinion in Systems Biology
https://www.readbyqxmd.com/read/28989987/towards-a-better-cancer-precision-medicine-systems-biology-meets-immunotherapy
#14
Bhavneet Bhinder, Olivier Elemento
Systems biology approaches that embrace the complexity of cancer are starting to gain traction in the development of new anticancer therapeutic strategies. In this review we describe how genomic analyses are helping improve our understanding of response to immunotherapy, a front-runner in cancer treatment. We argue that systems-level approaches are needed to help understand the concerted impact of tumor-specific and immune-specific molecular features on clinical outcomes, predict responders and unravel the complexity of tumor ecosystems...
April 2017: Current Opinion in Systems Biology
https://www.readbyqxmd.com/read/28691107/network-based-approaches-that-exploit-inferred-transcription-factor-activity-to-analyze-the-impact-of-genetic-variation-on-gene-expression
#15
Harmen J Bussemaker, Helen C Causton, Mina Fazlollahi, Eunjee Lee, Ivor Muroff
Over the past decade, a number of methods have emerged for inferring protein-level transcription factor activities in individual samples based on prior information about the structure of the gene regulatory network. We discuss how this has enabled new methods for dissecting trans-acting mechanisms that underpin genetic variation in gene expression.
April 2017: Current Opinion in Systems Biology
https://www.readbyqxmd.com/read/29226270/insights-into-the-role-of-somatic-mosaicism-in-the-brain
#16
Apuã C M Paquola, Jennifer A Erwin, Fred H Gage
Somatic mosaicism refers to the fact that cells within an organism have different genomes. It is now clear that somatic mosaicism occurs in all brains and that somatic mutations in a subset of cells can cause various rare neurodevelopmental disorders. However, for most individuals, the extent and consequences of somatic mosaicism are largely unknown. The complexity and unique features of the brain suggest that somatic mosaicism can play an important role in behavior and cognition. Here we review recent manuscripts showing instances of somatic mosaicism in the brain and estimating its extent and possible biological consequences...
February 2017: Current Opinion in Systems Biology
https://www.readbyqxmd.com/read/29177203/modeling-cancer-rearrangement-landscapes
#17
John Maciejowski, Marcin Imielinski
Cancer genome sequences contain footprints of somatic mutational processes, whose analysis in large tumor sequencing datasets has revealed novel mutational signatures, correlative features of variant topography, and complex events. Many of these analytic results have yet to reconciled with decades of mechanistic genome integrity research performed in controlled model systems. However, a new generation of genome-integrity experiments combining computational modeling, data analytics, and high-throughput sequencing are emerging to link mechanisms to patterns...
February 2017: Current Opinion in Systems Biology
https://www.readbyqxmd.com/read/29104946/an-operational-view-of-intercellular-signaling-pathways
#18
Yaron E Antebi, Nagarajan Nandagopal, Michael B Elowitz
Animal cells use a conserved repertoire of intercellular signaling pathways to communicate with one another. These pathways are well-studied from a molecular point of view. However, we often lack an "operational" understanding that would allow us to use these pathways to rationally control cellular behaviors. This requires knowing what dynamic input features each pathway perceives and how it processes those inputs to control downstream processes. To address these questions, researchers have begun to reconstitute signaling pathways in living cells, analyzing their dynamic responses to stimuli, and developing new functional representations of their behavior...
February 2017: Current Opinion in Systems Biology
https://www.readbyqxmd.com/read/28989986/data-resources-for-human-functional-genomics
#19
Kristin G Ardlie, Roderic Guigó
No abstract text is available yet for this article.
February 2017: Current Opinion in Systems Biology
https://www.readbyqxmd.com/read/28983521/topological-methods-for-genomics-present-and-future-directions
#20
Pablo G Cámara
Topological methods are emerging as a new set of tools for the analysis of large genomic datasets. They are mathematically grounded methods that extract information from the geometric structure of data. In the last few years, applications to evolutionary biology, cancer genomics, and the analysis of complex diseases have uncovered significant biological results, highlighting their utility for fulfilling some of the current analytic needs of genomics. In this review, the state of the art in the application of topological methods to genomics is summarized, and some of the present limitations and possible future developments are reviewed...
February 2017: Current Opinion in Systems Biology
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