Abstract：
:Cell classifiers are genetic logic circuits that transduce endogenous molecular inputs into cell-type-specific responses. Designing classifiers that achieve optimal differential response between specific cell types is a hard computational problem because it involves selection of endogenous inputs and optimization of both biochemical parameters and a logic function. To address this problem, we first derive an optimal set of biochemical parameters with the largest expected differential response over a diverse set of logic circuits, and second, we use these parameters in an evolutionary algorithm to select circuit inputs and optimize the logic function. Using this approach, we design experimentally feasible microRNA-based circuits capable of perfect discrimination for several real-world cell-classification tasks. We also find that under realistic cell-to-cell variation, circuit performance is comparable to standard cross-validation performance estimates. Our approach facilitates the generation of candidate circuits for experimental testing in therapeutic settings that require precise cell targeting, such as cancer therapy.
journal_name
Cell Systjournal_title
Cell systemsauthors
Mohammadi P,Beerenwinkel N,Benenson Ydoi
10.1016/j.cels.2017.01.003subject
Has Abstractpub_date
2017-02-22 00:00:00pages
207-218.e14issue
2eissn
2405-4712issn
2405-4720pii
S2405-4712(17)30003-0journal_volume
4pub_type
杂志文章相关文献
Cell Systems文献大全abstract：:Cancer evolution poses a central obstacle to cure, as resistant clones expand under therapeutic selection pressures. Genome sequencing of relapsed disease can nominate genomic alterations conferring resistance but sample collection lags behind, limiting therapeutic innovation. Genome-wide screens offer a complementary...
journal_title：Cell systems
pub_type： 杂志文章
doi：10.1016/j.cels.2019.10.002
更新日期：2020-01-22 00:00:00
abstract：:Alterations of circadian clock genes are associated with patient survival, tumor stage, and clinical subtype across various cancer types, highlighting the importance of timing in cancer treatment. ...
journal_title：Cell systems
pub_type： 评论
doi：10.1016/j.cels.2018.03.006
更新日期：2018-03-28 00:00:00
abstract：:Signaling proteins display remarkable cell-to-cell heterogeneity in their dynamic responses to stimuli, but the consequences of this heterogeneity remain largely unknown. For instance, the contribution of the dynamics of the innate immune transcription factor nuclear factor κB (NF-κB) to gene expression output is disp...
journal_title：Cell systems
pub_type： 杂志文章
doi：10.1016/j.cels.2017.03.010
更新日期：2017-04-26 00:00:00
abstract：:Overlap of RNA and protein networks reveals glia cells as key players for the development of symptomatic Alzheimer's disease in humans. ...
journal_title：Cell systems
pub_type： 评论,杂志文章
doi：10.1016/j.cels.2017.02.006
更新日期：2017-02-22 00:00:00
abstract：:Mechanistic models explicitly represent hypothesized biological knowledge. As such, they offer more generalizability than data-driven models. However, identifying model curation efforts that improve performance for mechanistic models is nontrivial. Here, we develop a solution to this problem for genome-scale metabolic...
journal_title：Cell systems
pub_type： 杂志文章
doi：10.1016/j.cels.2019.11.006
更新日期：2020-01-22 00:00:00
abstract：:One snapshot of the peer review process for "Cytoplasmic Amplification of Transcriptional Noise Generates Substantial Cell-to-Cell Variability" (Hansen et al., 2018). ...
journal_title：Cell systems
pub_type： 评论,杂志文章
doi：10.1016/j.cels.2018.10.003
更新日期：2018-10-24 00:00:00
abstract：:Translation of mRNA into protein is a fundamental yet complex biological process with multiple factors that can potentially affect its efficiency. Here, we study a stochastic model describing the traffic flow of ribosomes along the mRNA and identify the key parameters that govern the overall rate of protein synthesis,...
journal_title：Cell systems
pub_type： 杂志文章
doi：10.1016/j.cels.2019.12.003
更新日期：2020-02-26 00:00:00
abstract：: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 ...
journal_title：Cell systems
pub_type： 杂志文章,评审
doi：10.1016/j.cels.2017.04.006
更新日期：2017-05-24 00:00:00
abstract：:The human interactome is instrumental in the systems-level study of the cell and the contextualization of disease-associated gene perturbations. However, reference organismal interactomes do not capture the cell-type-specific context in which proteins and modules preferentially act. Here, we introduce SCINET, a comput...
journal_title：Cell systems
pub_type： 杂志文章
doi：10.1016/j.cels.2019.10.007
更新日期：2019-12-18 00:00:00
abstract：:Here, we outline p-Creode, a new algorithm to construct multi-branching cell lineage trajectories from single-cell data. Application of this platform to diverse sources of single-cell data demonstrates its robustness and scalability, while the discovery of a new origin for rare gut tuft cells showcases the utility of ...
journal_title：Cell systems
pub_type： 评论,杂志文章
doi：10.1016/j.cels.2017.12.015
更新日期：2018-01-24 00:00:00
abstract：:Establishing a quantitative connection between the population growth rate and the generation times of single cells is a prerequisite for understanding evolutionary dynamics of microbes. However, existing theories fail to account for the experimentally observed correlations between mother-daughter generation times that...
journal_title：Cell systems
pub_type： 杂志文章
doi：10.1016/j.cels.2017.08.015
更新日期：2017-10-25 00:00:00
abstract：:Living systems integrate biochemical reactions that determine the functional state of each cell. Reactions are primarily mediated by proteins. In proteomic studies, these have been treated as independent entities, disregarding their higher-level organization into complexes that affects their activity and/or function a...
journal_title：Cell systems
pub_type： 杂志文章
doi：10.1016/j.cels.2020.01.001
更新日期：2020-02-26 00:00:00
abstract：:Temporal interference (TI) is a non-invasive neurostimulation technique that utilizes high-frequency external electric fields to stimulate deep neuronal structures without affecting superficial, off-target structures. TI represents a potential breakthrough for treating conditions, such as Parkinson's disease and chron...
journal_title：Cell systems
pub_type： 杂志文章
doi：10.1016/j.cels.2020.10.004
更新日期：2020-12-16 00:00:00
abstract：:How do rich biological behaviors arise from bi-molecular collisions? ...
journal_title：Cell systems
pub_type： 杂志文章
doi：10.1016/j.cels.2015.09.006
更新日期：2015-09-23 00:00:00
abstract：:Hemizygous deletion of a gene in tumor cells frequently causes reduced expression of its encoded mRNA and protein, as well as reduced protein-but not mRNA-expression of other members in the same protein complex. ...
journal_title：Cell systems
pub_type： 评论,杂志文章
doi：10.1016/j.cels.2017.10.005
更新日期：2017-10-25 00:00:00
abstract：:One snapshot of the peer review process for "Critical Roles of the Pentose Phosphate Pathway and GLN3 in Isobutanol-Specific Tolerance in Yeast" (Kuroda et al., 2019). ...
journal_title：Cell systems
pub_type： 评论,杂志文章
doi：10.1016/j.cels.2020.01.005
更新日期：2020-02-26 00:00:00
abstract：:Racism and COVID-19 represent a pandemic on a pandemic for Blacks. The pandemics find themselves synergized to the detriment of Blacks and their health. The complexity of the combination of these pandemics are evident when examining the interplay between racist policing practices and health. ...
journal_title：Cell systems
pub_type： 杂志文章
doi：10.1016/j.cels.2020.07.002
更新日期：2020-07-22 00:00:00
abstract：:Effective design of combination therapies requires understanding the changes in cell physiology that result from drug interactions. Here, we show that the genome-wide transcriptional response to combinations of two drugs, measured at a rigorously controlled growth rate, can predict higher-order antagonism with a third...
journal_title：Cell systems
pub_type： 杂志文章
doi：10.1016/j.cels.2019.10.004
更新日期：2019-11-27 00:00:00
abstract：:Machine learning can be used to predict compounds acting synergistically, and this could greatly expand the universe of available potential treatments for diseases that are currently hidden in the dark chemical matter. ...
journal_title：Cell systems
pub_type： 杂志文章
doi：10.1016/j.cels.2015.12.005
更新日期：2015-12-23 00:00:00
abstract：:Patterning of periodic stripes during development requires mechanisms to control both stripe spacing and orientation. A number of models can explain how stripe spacing is controlled, including molecular mechanisms, such as Turing's reaction-diffusion model, as well as cell-based and mechanical mechanisms. However, how...
journal_title：Cell systems
pub_type： 杂志文章
doi：10.1016/j.cels.2015.12.001
更新日期：2015-12-23 00:00:00
abstract：: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...
journal_title：Cell systems
pub_type： 杂志文章
doi：10.1016/j.cels.2016.10.020
更新日期：2016-11-23 00:00:00
abstract：:Three studies demonstrate the potential of state-of-the-art mass spectrometry-based proteomics for rapid, deep characterization of proteomes. ...
journal_title：Cell systems
pub_type： 评论,杂志文章
doi：10.1016/j.cels.2016.03.002
更新日期：2016-03-23 00:00:00
abstract：:Despite improved methods for MHC affinity prediction, the vast majority of computationally predicted tumor neoantigens are not immunogenic experimentally, indicating that high-quality neoantigens are beyond current algorithms to discern. To enrich for neoantigens with the greatest likelihood of immunogenicity, we deve...
journal_title：Cell systems
pub_type： 杂志文章
doi：10.1016/j.cels.2019.08.009
更新日期：2019-10-23 00:00:00
abstract：:Isogenic cells in a common environment show substantial cell-to-cell variation in gene expression, often referred to as "expression noise." Here, we use multiple single-cell RNA-sequencing datasets to identify features associated with high or low expression noise in mouse embryonic stem cells. These include the core p...
journal_title：Cell systems
pub_type： 杂志文章
doi：10.1016/j.cels.2017.10.003
更新日期：2017-11-22 00:00:00
abstract：:Escherichia coli gene expression knockdown using synthetic small RNA (sRNA) can be fine-tuned by altering sRNA sequences to modulate target mRNA-binding ability, but this requires thorough checking for off-target effects. Here, we present an sRNA gene expression knockdown system fine-tuned by using different promoters...
journal_title：Cell systems
pub_type： 杂志文章
doi：10.1016/j.cels.2017.08.016
更新日期：2017-10-25 00:00:00
abstract：:The construction of complex gene-regulatory networks requires both inhibitory and upregulatory modules. However, the vast majority of RNA-based regulatory "parts" are inhibitory. Using a synthetic biology approach combined with SHAPE-seq, we explored the regulatory effect of RNA-binding protein (RBP)-RNA interactions ...
journal_title：Cell systems
pub_type： 杂志文章
doi：10.1016/j.cels.2019.04.007
更新日期：2019-07-24 00:00:00
abstract：:While decades of research have elucidated many steps of the alphavirus lifecycle, the earliest replication dynamics have remained unclear. This missing time window has obscured early replicase strand-synthesis behavior and prevented elucidation of how the first events of infection might influence subsequent viral comp...
journal_title：Cell systems
pub_type： 杂志文章
doi：10.1016/j.cels.2020.12.005
更新日期：2021-01-21 00:00:00
abstract：:Adenocarcinoma accounts for more than 40% of lung malignancy, and microscopic pathology evaluation is indispensable for its diagnosis. However, how histopathology findings relate to molecular abnormalities remains largely unknown. Here, we obtained H&E-stained whole-slide histopathology images, pathology reports, RNA ...
journal_title：Cell systems
pub_type： 杂志文章
doi：10.1016/j.cels.2017.10.014
更新日期：2017-12-27 00:00:00
abstract：:Two studies show that noise is a key ingredient of new mechanisms for entraining the NF-κB system. ...
journal_title：Cell systems
pub_type： 杂志文章
doi：10.1016/j.cels.2016.12.008
更新日期：2016-12-21 00:00:00
abstract：:Large-scale single-cell RNA sequencing (scRNA-seq) studies that profile hundreds of thousands of cells are becoming increasingly common, overwhelming existing analysis pipelines. Here, we describe how to enhance and accelerate single-cell data analysis by summarizing the transcriptomic heterogeneity within a dataset u...
journal_title：Cell systems
pub_type： 杂志文章
doi：10.1016/j.cels.2019.05.003
更新日期：2019-06-26 00:00:00
