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https://read.qxmd.com/read/30785874/machine-learning-analysis-of-gene-expression-data-reveals-novel-diagnostic-and-prognostic-biomarkers-and-identifies-therapeutic-targets-for-soft-tissue-sarcomas
#1
David G P van IJzendoorn, Karoly Szuhai, Inge H Briaire-de Bruijn, Marie Kostine, Marieke L Kuijjer, Judith V M G Bovée
Based on morphology it is often challenging to distinguish between the many different soft tissue sarcoma subtypes. Moreover, outcome of disease is highly variable even between patients with the same disease. Machine learning on transcriptome sequencing data could be a valuable new tool to understand differences between and within entities. Here we used machine learning analysis to identify novel diagnostic and prognostic markers and therapeutic targets for soft tissue sarcomas. Gene expression data was used from the Cancer Genome Atlas, the Genotype-Tissue Expression data and the French Sarcoma Group...
February 20, 2019: PLoS Computational Biology
https://read.qxmd.com/read/30780338/diffusion-dynamics-laws-in-stochastic-reaction-networks
#2
Tan Van Vu, Yoshihiko Hasegawa
Many biological activities are induced by cellular chemical reactions of diffusing reactants. The dynamics of such systems can be captured by stochastic reaction networks. A recent numerical study has shown that diffusion can significantly enhance the fluctuations in gene regulatory networks. However, the universal relation between diffusion and stochastic system dynamics remains veiled. Within the approximation of reaction-diffusion master equation (RDME), we find general relation that the steady-state distribution in complex balanced networks is diffusion-independent...
January 2019: Physical Review. E
https://read.qxmd.com/read/30779734/multi-modality-in-gene-regulatory-networks-with-slow-promoter-kinetics
#3
Muhammad Ali Al-Radhawi, Domitilla Del Vecchio, Eduardo D Sontag
Phenotypical variability in the absence of genetic variation often reflects complex energetic landscapes associated with underlying gene regulatory networks (GRNs). In this view, different phenotypes are associated with alternative states of complex nonlinear systems: stable attractors in deterministic models or modes of stationary distributions in stochastic descriptions. We provide theoretical and practical characterizations of these landscapes, specifically focusing on stochastic Slow Promoter Kinetics (SPK), a time scale relevant when transcription factor binding and unbinding are affected by epigenetic processes like DNA methylation and chromatin remodeling...
February 19, 2019: PLoS Computational Biology
https://read.qxmd.com/read/30779198/large-ancestral-effective-population-size-explains-the-difficult-phylogenetic-placement-of-owl-monkeys
#4
Carlos G Schrago, Hector N Seuánez
The phylogenetic position of owl monkeys, grouped in the genus Aotus, has been a controversial issue for understanding Neotropical primate evolution. Explanations of the difficult phylogenetic assignment of owl monkeys have been elusive, frequently relying on insufficient data (stochastic error) or scenarios of rapid speciation (adaptive radiation) events. Using a coalescent-based approach, we explored the population-level mechanisms likely explaining these topological discrepancies. We examined the topological variance of 2,192 orthologous genes shared between representatives of the three major Cebidae lineages and the outgroup...
February 18, 2019: American Journal of Primatology
https://read.qxmd.com/read/30777763/bayesian-estimation-for-stochastic-gene-expression-using-multifidelity-models
#5
Huy D Vo, Zachary R Fox, Ania Baetica, Brian Munsky
The finite state projection (FSP) approach to solving the chemical master equation has enabled successful inference of discrete stochastic models to predict single-cell gene regulation dynamics. Unfortunately, the FSP approach is highly computationally intensive for all but the simplest models, an issue that is highly problematic when parameter inference and uncertainty quantification takes enormous numbers of parameter evaluations. To address this issue, we propose two new computational methods for the Bayesian inference of stochastic gene expression parameters given single-cell experiments...
February 19, 2019: Journal of Physical Chemistry. B
https://read.qxmd.com/read/30774969/frequency-of-disturbance-alters-diversity-function-and-underlying-assembly-mechanisms-of-complex-bacterial-communities
#6
Ezequiel Santillan, Hari Seshan, Florentin Constancias, Daniela I Drautz-Moses, Stefan Wuertz
Disturbance is known to affect the ecosystem structure, but predicting its outcomes remains elusive. Similarly, community diversity is believed to relate to ecosystem functions, yet the underlying mechanisms are poorly understood. Here, we tested the effect of disturbance on the structure, assembly, and ecosystem function of complex microbial communities within an engineered system. We carried out a microcosm experiment where activated sludge bioreactors operated in daily cycles were subjected to eight different frequency levels of augmentation with a toxic pollutant, from never (undisturbed) to every day (press-disturbed), for 35 days...
2019: NPJ Biofilms and Microbiomes
https://read.qxmd.com/read/30770771/considerations-for-the-use-of-cre-recombinase-for-conditional-gene-deletion-in-the-mouse-lens
#7
Phuong T Lam, Stephanie L Padula, Thanh V Hoang, Justin E Poth, Lin Liu, Chun Liang, Adam S LeFever, Lindsay M Wallace, Ruth Ashery-Padan, Penny K Riggs, Jordan E Shields, Ohad Shaham, Sheldon Rowan, Nadean L Brown, Tom Glaser, Michael L Robinson
BACKGROUND: Despite a number of different transgenes that can mediate DNA deletion in the developing lens, each has unique features that can make a given transgenic line more or less appropriate for particular studies. The purpose of this work encompasses both a review of transgenes that lead to the expression of Cre recombinase in the lens and a comparative analysis of currently available transgenic lines with a particular emphasis on the Le-Cre and P0-3.9GFPCre lines that can mediate DNA deletion in the lens placode...
February 15, 2019: Human Genomics
https://read.qxmd.com/read/30767891/a-y-chromosome-shredding-gene-drive-for-controlling-pest-vertebrate-populations
#8
Thomas Aa Prowse, Fatwa Adikusuma, Phillip Cassey, Paul Thomas, Joshua V Ross
Self-replicating gene drives that modify sex ratios or infer a fitness cost could be used to control populations of invasive alien species. The targeted deletion of Y sex chromosomes using CRISPR technology offers a new approach for sex bias that could be incorporated within gene-drive designs. We introduce a novel gene-drive strategy termed Y-CHromosome deletion using Orthogonal Programmable Endonucleases (Y-CHOPE), incorporating a programmable endonuclease that 'shreds' the Y chromosome, thereby converting XY males into fertile XO females...
February 15, 2019: ELife
https://read.qxmd.com/read/30765722/quantifying-dynamic-mechanisms-of-auto-regulation-in-escherichia-coli-with-synthetic-promoter-in-response-to-varying-external-phosphate-levels
#9
Cansu Uluşeker, Jesús Torres-Bacete, José L García, Martin M Hanczyc, Juan Nogales, Ozan Kahramanoğulları
Escherichia coli have developed one of the most efficient regulatory response mechanisms to phosphate starvation. The machinery involves a cascade with a two-component system (TCS) that relays the external signal to the genetic circuit, resulting in a feedback response. Achieving a quantitative understanding of this system has implications in synthetic biology and biotechnology, for example, in applications for wastewater treatment. To this aim, we present a computational model and experimental results with a detailed description of the TCS, consisting of PhoR and PhoB, together with the mechanisms of gene expression...
February 14, 2019: Scientific Reports
https://read.qxmd.com/read/30765529/concentric-organization-of-a-and-b-type-lamins-predicts-their-distinct-roles-in-the-spatial-organization-and-stability-of-the-nuclear-lamina
#10
Bruce Nmezi, Jianquan Xu, Rao Fu, Travis J Armiger, Guillermo Rodriguez-Bey, Juliana S Powell, Hongqiang Ma, Mara Sullivan, Yiping Tu, Natalie Y Chen, Stephen G Young, Donna B Stolz, Kris Noel Dahl, Yang Liu, Quasar S Padiath
The nuclear lamina is an intermediate filament meshwork adjacent to the inner nuclear membrane (INM) that plays a critical role in maintaining nuclear shape and regulating gene expression through chromatin interactions. Studies have demonstrated that A- and B-type lamins, the filamentous proteins that make up the nuclear lamina, form independent but interacting networks. However, whether these lamin subtypes exhibit a distinct spatial organization or whether their organization has any functional consequences is unknown...
February 14, 2019: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/30765469/a-tale-of-two-genes-divergent-evolutionary-fate-of-haptoglobin-and-hemopexin-in-hemoglobinless-antarctic-icefishes
#11
Kevin T Bilyk, Xuan Zhuang, Katherine R Murphy, C-H Christina Cheng
Evolution of Antarctic notothenioid fishes in the isolated freezing Southern Ocean have led to remarkable trait gains and losses. One of the most extraordinary was the loss of the major oxygen carrier hemoglobin (Hb) in the icefishes (family Channichthyidae). While the mechanisms of this loss and the resulting compensatory changes have been well studied, the impact of Hb loss on the network of genes that once supported its recycling and disposal has remained unexplored. Here we report the functional fate and underlying molecular changes of two such key Hb-supporting proteins across the icefish family - haptoglobin (Hp) and hemopexin (Hx), crucial in removing cytotoxic free Hb and heme respectively...
February 14, 2019: Journal of Experimental Biology
https://read.qxmd.com/read/30763315/iris-eda-an-integrated-rna-seq-interpretation-system-for-gene-expression-data-analysis
#12
Brandon Monier, Adam McDermaid, Cankun Wang, Jing Zhao, Allison Miller, Anne Fennell, Qin Ma
Next-Generation Sequencing has made available substantial amounts of large-scale Omics data, providing unprecedented opportunities to understand complex biological systems. Specifically, the value of RNA-Sequencing (RNA-Seq) data has been confirmed in inferring how gene regulatory systems will respond under various conditions (bulk data) or cell types (single-cell data). RNA-Seq can generate genome-scale gene expression profiles that can be further analyzed using correlation analysis, co-expression analysis, clustering, differential gene expression (DGE), among many other studies...
February 14, 2019: PLoS Computational Biology
https://read.qxmd.com/read/30761456/exact-variance-reduced-simulation-of-lattice-continuous-time-markov-chains-with-applications-in-reaction-networks
#13
P A Maginnis, M West, G E Dullerud
We propose an algorithm to reduce the variance of Monte Carlo simulation for the class of countable-state, continuous-time Markov chains, or lattice CTMCs. This broad class of systems includes all processes that can be represented using a random-time-change representation, in particular reaction networks. Numerical studies demonstrate order-of-magnitude reduction in MSE for Monte Carlo mean estimates using our approach for both linear and nonlinear systems. The algorithm works by simulating pairs of negatively correlated, identically distributed sample trajectories of the stochastic process and using them to produce variance-reduced, unbiased Monte Carlo estimates, effectively generalizing the method of antithetic variates into the domain of stochastic processes...
February 13, 2019: Bulletin of Mathematical Biology
https://read.qxmd.com/read/30756455/novel-approach-to-quantitative-spatial-gene-expression-uncovers-genetic-stochasticity-in-the-developing-drosophila-eye
#14
Sammi Ali, Sarah A Signor, Konstantin Kozlov, Sergey V Nuzhdin
Robustness in development allows for the accumulation of genetically based variation in expression. However, this variation is usually examined in response to large perturbations, and examination of this variation has been limited to being spatial, or quantitative, but because of technical restrictions not both. Here we bridge these gaps by investigating replicated quantitative spatial gene expression using rigorous statistical models, in different genotypes, sexes, and species (Drosophila melanogaster and D...
February 12, 2019: Evolution & Development
https://read.qxmd.com/read/30753839/spatial-stochastic-modelling-of-synthetic-gene-regulatory-networks
#15
Cicely K Macnamara, Elaine I Mitchell, Mark A J Chaplain
Transcription factors are important molecules which control the levels of mRNA and proteins within cells by modulating the process of transcription (the mechanism by which mRNA is produced within cells) and hence translation (the mechanism by which proteins are produced within cells). Transcription factors are part of a wider family of molecular interaction networks known as gene regulatory networks (GRNs) which play an important role in key cellular processes such as cell division and apoptosis (e.g. the p53-Mdm2, NFκB pathways)...
February 9, 2019: Journal of Theoretical Biology
https://read.qxmd.com/read/30745378/mitochondrial-dna-fitness-depends-on-nuclear-genetic-background-in-drosophila
#16
Jim A Mossman, Jennifer Y Ge, Freddy Navarro, David M Rand
Mitochondrial DNA (mtDNA) has been one of the most extensively studied molecules in ecological, evolutionary and clinical genetics. In its early application in evolutionary genetics, mtDNA was assumed to be a selectively neutral marker conferring negligible fitness consequences for its host. However, this dogma has been overturned in recent years due to now extensive evidence for non-neutral evolutionary dynamics. Since mtDNA proteins physically interact with nuclear proteins to provide the mitochondrial machinery for aerobic ATP production, among other cell functions, co-variation of the respective genes is predicted to affect organismal fitness...
February 11, 2019: G3: Genes—Genomes—Genetics
https://read.qxmd.com/read/30742040/fast-interpolation-based-t-sne-for-improved-visualization-of-single-cell-rna-seq-data
#17
George C Linderman, Manas Rachh, Jeremy G Hoskins, Stefan Steinerberger, Yuval Kluger
t-distributed stochastic neighbor embedding (t-SNE) is widely used for visualizing single-cell RNA-sequencing (scRNA-seq) data, but it scales poorly to large datasets. We dramatically accelerate t-SNE, obviating the need for data downsampling, and hence allowing visualization of rare cell populations. Furthermore, we implement a heatmap-style visualization for scRNA-seq based on one-dimensional t-SNE for simultaneously visualizing the expression patterns of thousands of genes. Software is available at https://github...
February 11, 2019: Nature Methods
https://read.qxmd.com/read/30738198/codseqgen-a-tool-for-generating-synonymous-coding-sequences-with-desired-gc-contents
#18
Abdulrakeeb M Al-Ssulami, Aqil M Azmi, Muhammad Hussain
Identification of regulatory elements is essential for understanding the mechanism behind regulating gene expression. These regulatory elements-located in or near gene-bind to proteins called transcription factors to initiate the transcription process. Their occurrences are influenced by the GC-content or nucleotide composition. For generating synthetic coding sequences with pre-specified amino acid sequence and desired GC-content, there exist two stochastic methods, multinomial and maximum entropy. Both methods rely on the probability of choosing the codon synonymous for usage in regard to a specific amino acid...
February 6, 2019: Genomics
https://read.qxmd.com/read/30736279/quantifying-brca1-and-brca2-mrna-isoform-expression-levels-in-single-cells
#19
Vanessa L Lattimore, John F Pearson, Arthur E Morley-Bunker, kConFab Investigators, Amanda B Spurdle, Bridget A Robinson, Margaret J Currie, Logan C Walker
BRCA1 and BRCA2 spliceogenic variants are often associated with an elevated risk of breast and ovarian cancers. Analyses of BRCA1 and BRCA2 splicing patterns have traditionally used technologies that sample a population of cells but do not account for the variation that may be present between individual cells. This novel proof of concept study utilises RNA in situ hybridisation to measure the absolute expression of BRCA1 and BRCA2 mRNA splicing events in single lymphoblastoid cells containing known spliceogenic variants ( BRCA1 c...
February 6, 2019: International Journal of Molecular Sciences
https://read.qxmd.com/read/30725340/the-problem-of-non-shared-environment-in-behavioral-genetics
#20
REVIEW
Oleg N Tikhodeyev, Оlga V Shcherbakova
The role of non-shared environment (NSE) in the development of psychological traits is usually comparable with that of the genotype. However, no specific factors of NSE with significant impact on such traits have been discovered so far. We propose that the current failures in understanding the origin of NSE are at least partly due to the fact that behavioral genetics has left out one of the key sources of phenotypic variation. This source is the intrinsic stochasticity of molecular processes underlying individual development...
February 6, 2019: Behavior Genetics
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