Abstract：
: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. We applied eADAGE to a compendium of Pseudomonas aeruginosa gene expression profiling experiments performed in 78 media. eADAGE revealed a phosphate starvation response controlled by PhoB in media with moderate phosphate and predicted that a second stimulus provided by the sensor kinase, KinB, is required for this PhoB activation. We validated this relationship using both targeted and unbiased genetic approaches. eADAGE, which captures stable biological patterns, enables cross-experiment comparisons that can highlight measured but undiscovered relationships.
journal_name
Cell Systjournal_title
Cell systemsauthors
Tan J,Doing G,Lewis KA,Price CE,Chen KM,Cady KC,Perchuk B,Laub MT,Hogan DA,Greene CSdoi
10.1016/j.cels.2017.06.003subject
Has Abstractpub_date
2017-07-26 00:00:00pages
63-71.e6issue
1eissn
2405-4712issn
2405-4720pii
S2405-4712(17)30231-4journal_volume
5pub_type
杂志文章相关文献
Cell Systems文献大全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：: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：:It is known that the calcium-dependent transcription factor NFAT initiates transcription in response to pulsatile loads of calcium signal. However, the relative contributions of calcium oscillation frequency, amplitude, and duty cycle to transcriptional activity remain unclear. Here, we engineer HeLa cells to permit o...
journal_title：Cell systems
pub_type： 杂志文章
doi：10.1016/j.cels.2016.03.010
更新日期：2016-04-27 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：:Small RNA sequencing has been widely adopted to study the diversity of extracellular RNAs (exRNAs) in biofluids; however, the analysis of exRNA samples can be challenging: they are vulnerable to contamination and artifacts from different isolation techniques, present in lower concentrations than cellular RNA, and occa...
journal_title：Cell systems
pub_type： 杂志文章
doi：10.1016/j.cels.2019.03.004
更新日期：2019-04-24 00:00:00
abstract：:Recent advances in synthetic biology and biological system engineering have allowed the design and construction of engineered live biotherapeutics targeting a range of human clinical applications. In this review, we outline how systems approaches have been used to move from simple constitutive systems, where a single ...
journal_title：Cell systems
pub_type： 杂志文章,评审
doi：10.1016/j.cels.2018.06.008
更新日期：2018-07-25 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：: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：: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：: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：: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：: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：: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：:Although genetic mutations that alter organisms' average lifespans have been identified in aging research, our understanding of the dynamic changes during aging remains limited. Here, we integrate single-cell imaging, microfluidics, and computational modeling to investigate phenotypic divergence and cellular heterogen...
journal_title：Cell systems
pub_type： 杂志文章
doi：10.1016/j.cels.2019.02.002
更新日期：2019-03-27 00:00:00
abstract：:Medically induced loss of consciousness (mLOC) during anesthesia is associated with a macroscale breakdown of brain connectivity, yet the neural microcircuit correlates of mLOC remain unknown. To explore this, we applied different analytical approaches (t-SNE/watershed segmentation, affinity propagation clustering, PC...
journal_title：Cell systems
pub_type： 杂志文章
doi：10.1016/j.cels.2019.03.007
更新日期：2019-05-22 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：:Studying autism genes in the context of the protein complexes to which they belong illustrates the potential of network-centric approaches for understanding complex genetic disease. ...
journal_title：Cell systems
pub_type： 杂志文章
doi：10.1016/j.cels.2015.11.004
更新日期：2015-11-25 00:00:00
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：: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
abstract：:The tumor-suppressing transcription factor p53 is highly conserved at the protein level and plays a key role in the DNA damage response. One important aspect of p53 regulation is its dynamics in response to DNA damage, which include oscillations. Here, we observe that, while the qualitative oscillatory nature of p53 d...
journal_title：Cell systems
pub_type： 杂志文章
doi：10.1016/j.cels.2017.09.012
更新日期：2017-10-25 00:00:00
abstract：:Systematic assessment of tyrosine kinase-substrate relationships is fundamental to a better understanding of cellular signaling and its profound alterations in human diseases such as cancer. In human cells, such assessments are confounded by complex signaling networks, feedback loops, conditional activity, and intra-k...
journal_title：Cell systems
pub_type： 杂志文章
doi：10.1016/j.cels.2017.08.001
更新日期：2017-08-23 00:00:00
abstract：:It is unclear how standing genetic variation affects the prognosis of prostate cancer patients. To provide one controlled answer to this problem, we crossed a dominant, penetrant mouse model of prostate cancer to Diversity Outbred mice, a collection of animals that carries over 40 million SNPs. Integration of disease ...
journal_title：Cell systems
pub_type： 杂志文章
doi：10.1016/j.cels.2016.10.018
更新日期：2017-01-25 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：:Many data sets exhibit well-defined structure that can be exploited to design faster search tools, but it is not always clear when such acceleration is possible. Here we introduce a framework for similarity search based on characterizing a data set's entropy and fractal dimension. We prove that searching scales in tim...
journal_title：Cell systems
pub_type： 杂志文章
doi：10.1016/j.cels.2015.08.004
更新日期：2015-08-26 00:00:00
abstract：:Accurately translating genotype to phenotype requires accounting for the functional impact of genetic variation at many biological scales. Here we present a strategy for genotype-phenotype reasoning based on existing knowledge of cellular subsystems. These subsystems and their hierarchical organization are defined by ...
journal_title：Cell systems
pub_type： 杂志文章
doi：10.1016/j.cels.2016.02.003
更新日期：2016-02-24 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：:Clinically used RAF inhibitors are ineffective in RAS mutant tumors because they enhance homo- and heterodimerization of RAF kinases, leading to paradoxical activation of ERK signaling. Overcoming enhanced RAF dimerization and the resulting resistance is a challenge for drug design. Combining multiple inhibitors could...
journal_title：Cell systems
pub_type： 杂志文章
doi：10.1016/j.cels.2018.06.002
更新日期：2018-08-22 00:00:00
abstract：:We combine a genome-scale RNAi screen in mouse epiblast stem cells (EpiSCs) with genetic interaction, protein localization, and "protein-level dependency" studies-a systematic technique that uncovers post-transcriptional regulation-to delineate the network of factors that control the expression of Oct4, a key regulato...
journal_title：Cell systems
pub_type： 杂志文章
doi：10.1016/j.cels.2015.08.002
更新日期：2015-08-26 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：:The accumulation of protein damage in aging organisms is thought to contribute to many aging-related diseases. Yet the properties determining which proteins are most susceptible remain poorly understood. Are certain conformations more vulnerable? Which chaperones are the main guardians? We address these questions with...
journal_title：Cell systems
pub_type： 杂志文章
doi：10.1016/j.cels.2018.05.001
更新日期：2018-06-27 00:00:00
