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https://www.readbyqxmd.com/read/28910283/stochastic-principles-governing-alternative-splicing-of-rna
#1
Jianfei Hu, Eli Boritz, William Wylie, Daniel C Douek
The dominance of the major transcript isoform relative to other isoforms from the same gene generated by alternative splicing (AS) is essential to the maintenance of normal cellular physiology. However, the underlying principles that determine such dominance remain unknown. Here, we analyzed the physical AS process and found that it can be modeled by a stochastic minimization process, which causes the scaled expression levels of all transcript isoforms to follow the same Weibull extreme value distribution. Surprisingly, we also found a simple equation to describe the median frequency of transcript isoforms of different dominance...
September 14, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28904110/the-chromatin-accessibility-signature-of-human-immune-aging-stems-from-cd8-t-cells
#2
Duygu Ucar, Eladio J Márquez, Cheng-Han Chung, Radu Marches, Robert J Rossi, Asli Uyar, Te-Chia Wu, Joshy George, Michael L Stitzel, A Karolina Palucka, George A Kuchel, Jacques Banchereau
Aging is linked to deficiencies in immune responses and increased systemic inflammation. To unravel the regulatory programs behind these changes, we applied systems immunology approaches and profiled chromatin accessibility and the transcriptome in PBMCs and purified monocytes, B cells, and T cells. Analysis of samples from 77 young and elderly donors revealed a novel and robust aging signature in PBMCs, with simultaneous systematic chromatin closing at promoters and enhancers associated with T cell signaling and a potentially stochastic chromatin opening mostly found at quiescent and repressed sites...
September 13, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28903980/uniform-gene-expression-in-embryos-is-achieved-by-temporal-averaging-of-transcription-noise
#3
L Carine Stapel, Christoph Zechner, Nadine L Vastenhouw
Transcription is often stochastic. This is seemingly incompatible with the importance of gene expression during development. Here we show that during zebrafish embryogenesis, transcription activation is stochastic due to (1) genes acquiring transcriptional competence at different times in different cells, (2) differences in cell cycle stage between cells, and (3) the stochastic nature of transcription. Initially, stochastic transcription causes large cell-to-cell differences in transcript levels. However, variability is reduced by lengthening cell cycles and the accumulation of transcription events in each cell...
September 13, 2017: Genes & Development
https://www.readbyqxmd.com/read/28893855/mitigating-mitochondrial-genome-erosion-without-recombination
#4
Arunas L Radzvilavicius, Hanna Kokko, Joshua R Christie
Mitochondria are ATP-producing organelles of bacterial ancestry that played a key role in the origin and early evolution of complex eukaryotic cells. Most modern eukaryotes transmit mitochondrial genes uniparentally, often without recombination among genetically divergent organelles. While this asymmetric inheritance maintains the efficacy of purifying selection at the level of the cell, the absence of recombination could also make the genome susceptible to Muller's ratchet. How mitochondria escape this irreversible defect accumulation is a fundamental unsolved question...
September 11, 2017: Genetics
https://www.readbyqxmd.com/read/28881987/efficient-simulation-of-intrinsic-extrinsic-and-external-noise-in-biochemical-systems
#5
Dennis Pischel, Kai Sundmacher, Robert J Flassig
Motivation: Biological cells operate in a noisy regime influenced by intrinsic, extrinsic and external noise, which leads to large differences of individual cell states. Stochastic effects must be taken into account to characterize biochemical kinetics accurately. Since the exact solution of the chemical master equation, which governs the underlying stochastic process, cannot be derived for most biochemical systems, approximate methods are used to obtain a solution. Results: In this study, a method to efficiently simulate the various sources of noise simultaneously is proposed and benchmarked on several examples...
July 15, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28881959/maboss-2-0-an-environment-for-stochastic-boolean-modeling
#6
Gautier Stoll, Barthélémy Caron, Eric Viara, Aurélien Dugourd, Andrei Zinovyev, Aurélien Naldi, Guido Kroemer, Emmanuel Barillot, Laurence Calzone
Motivation: Modeling of signaling pathways is an important step towards the understanding and the treatment of diseases such as cancers, HIV or auto-immune diseases. MaBoSS is a software that allows to simulate populations of cells and to model stochastically the intracellular mechanisms that are deregulated in diseases. MaBoSS provides an output of a Boolean model in the form of time-dependent probabilities, for all biological entities (genes, proteins, phenotypes, etc.) of the model...
July 15, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28878283/rate-limiting-steps-in-transcription-dictate-sensitivity-to-variability-in-cellular-components
#7
Jarno Mäkelä, Vinodh Kandavalli, Andre S Ribeiro
Cell-to-cell variability in cellular components generates cell-to-cell diversity in RNA and protein production dynamics. As these components are inherited, this should also cause lineage-to-lineage variability in these dynamics. We conjectured that these effects on transcription are promoter initiation kinetics dependent. To test this, first we used stochastic models to predict that variability in the numbers of molecules involved in upstream processes, such as the intake of inducers from the environment, acts only as a transient source of variability in RNA production numbers, while variability in the numbers of a molecular species controlling transcription of an active promoter acts as a constant source...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28854270/hypermethylation-of-the-non-imprinted-maternal-meg3-and-paternal-mest-alleles-is-highly-variable-among-normal-individuals
#8
Larissa Haertle, Anna Maierhofer, Julia Böck, Harald Lehnen, Yvonne Böttcher, Matthias Blüher, Martin Schorsch, Ramya Potabattula, Nady El Hajj, Silke Appenzeller, Thomas Haaf
Imprinted genes show parent-specific activity (functional haploidy), which makes them particularly vulnerable to epigenetic dysregulation. Here we studied the methylation profiles of oppositely imprinted genes at single DNA molecule resolution by two independent parental allele-specific deep bisulfite sequencing (DBS) techniques. Using Roche (GSJunior) next generation sequencing technology, we analyzed the maternally imprinted MEST promoter and the paternally imprinted MEG3 intergenic (IG) differentially methylated region (DMR) in fetal cord blood, adult blood, and visceral adipose tissue...
2017: PloS One
https://www.readbyqxmd.com/read/28851932/genomic-plasticity-and-rapid-host-switching-can-promote-the-evolution-of-generalism-a-case-study-in-the-zoonotic-pathogen-campylobacter
#9
Dan J Woodcock, Peter Krusche, Norval J C Strachan, Ken J Forbes, Frederick M Cohan, Guillaume Méric, Samuel K Sheppard
Horizontal gene transfer accelerates bacterial adaptation to novel environments, allowing selection to act on genes that have evolved in multiple genetic backgrounds. This can lead to ecological specialization. However, little is known about how zoonotic bacteria maintain the ability to colonize multiple hosts whilst competing with specialists in the same niche. Here we develop a stochastic evolutionary model and show how genetic transfer of host segregating alleles, distributed as predicted for niche specifying genes, and the opportunity for host transition could interact to promote the emergence of host generalist lineages of the zoonotic bacterium Campylobacter...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28842224/an-efficient-and-assumption-free-method-to-approximate-protein-level-distribution-in-the-two-states-gene-expression-model
#10
Bingxiang Xu, Hao Ge, Zhihua Zhang
Stochastic fluctuations at each step of gene expression might influence protein levels distributions across cell populations. However, current methods to model protein distribution of intrinsic gene expression dynamics are either computationally inefficient or rely on ad hoc assumptions, e.g., that the gene is always active. Taking advantage of the simple form of lower-order moments of distribution, we developed an efficient and assumption-free protein distribution approximation method (EFPD), for the two state gene expression model to accurately approximate the distribution...
August 24, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28837855/use-it-or-average-it-stochasticity-in-plant-development
#11
REVIEW
Adrienne Hk Roeder
A process that is stochastic has a probabilistic or randomly determined outcome. At the molecular level, all processes are stochastic; but development is highly reproducible, suggesting that plants and other multicellular organisms have evolved mechanisms to ensure robustness (achieving correct development despite stochastic and environmental perturbations). Mechanisms of robustness can be discovered through isolating mutants with increased variability in phenotype; such mutations do not necessarily change the average phenotype...
August 21, 2017: Current Opinion in Plant Biology
https://www.readbyqxmd.com/read/28835372/pervasive-coexpression-of-spatially-proximal-genes-is-buffered-at-the-protein-level
#12
Georg Kustatscher, Piotr Grabowski, Juri Rappsilber
Genes are not randomly distributed in the genome. In humans, 10% of protein-coding genes are transcribed from bidirectional promoters and many more are organised in larger clusters. Intriguingly, neighbouring genes are frequently coexpressed but rarely functionally related. Here we show that coexpression of bidirectional gene pairs, and closeby genes in general, is buffered at the protein level. Taking into account the 3D architecture of the genome, we find that co-regulation of spatially close, functionally unrelated genes is pervasive at the transcriptome level, but does not extend to the proteome...
August 23, 2017: Molecular Systems Biology
https://www.readbyqxmd.com/read/28831492/quantitative-profiling-of-innate-immune-activation-by-viral-infection-in-single-cells
#13
Andrea C Timm, Jay W Warrick, John Yin
Cells infected by viruses can exhibit diverse patterns of viral and cellular gene expression. The patterns arise in part from the stochastic or noisy reaction kinetics associated with the small number of genomes, enzymes, and other molecules that typically initiate virus replication and activate cellular anti-viral defenses. It is not known what features, if any, of the early viral or cellular gene expression correlate with later processes of viral replication or cell survival. Here we used two fluorescent reporters to visualize innate immune activation of human prostate cancer (PC3) cells against infection by vesicular stomatitis virus...
September 18, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28829770/combinatorial-regulation-of-a-blimp1-prdm1-enhancer-in-the-mouse-retina
#14
Taylor S Mills, Tatiana Eliseeva, Stephanie M Bersie, Grace Randazzo, Jhenya Nahreini, Ko Uoon Park, Joseph A Brzezinski
The mouse retina comprises seven major cell types that exist in differing proportions. They are generated from multipotent progenitors in a stochastic manner, such that the relative frequency of any given type generated changes over time. The mechanisms determining the proportions of each cell type are only partially understood. Photoreceptors and bipolar interneurons are derived from cells that express Otx2. Within this population, Blimp1 (Prdm1) helps set the balance between photoreceptors and bipolar cells by suppressing bipolar identity in most of the cells...
2017: PloS One
https://www.readbyqxmd.com/read/28828032/integration-of-multiple-genomic-data-sources-in-a-bayesian-cox-model-for-variable-selection-and-prediction
#15
Tabea Treppmann, Katja Ickstadt, Manuela Zucknick
Bayesian variable selection becomes more and more important in statistical analyses, in particular when performing variable selection in high dimensions. For survival time models and in the presence of genomic data, the state of the art is still quite unexploited. One of the more recent approaches suggests a Bayesian semiparametric proportional hazards model for right censored time-to-event data. We extend this model to directly include variable selection, based on a stochastic search procedure within a Markov chain Monte Carlo sampler for inference...
2017: Computational and Mathematical Methods in Medicine
https://www.readbyqxmd.com/read/28821587/drift-induced-selection-between-male-and-female-heterogamety
#16
Carl Veller, Pavitra Muralidhar, George W A Constable, Martin A Nowak
Evolutionary transitions between male and female heterogamety are common in both vertebrates and invertebrates. Theoretical studies of these transitions have found that, when all genotypes are equally fit, continuous paths of intermediate equilibria link the two sex chromosome systems. This observation has led to a belief that neutral evolution along these paths can drive transitions, and that arbitrarily small fitness differences among sex chromosome genotypes can determine the system to which evolution leads...
August 16, 2017: Genetics
https://www.readbyqxmd.com/read/28809965/hill-kinetics-as-a-noise-filter-the-role-of-transcription-factor-autoregulation-in-gene-cascades
#17
Anna Ochab-Marcinek, Jakub Jędrak, Marcin Tabaka
An intuition based on deterministic models of chemical kinetics is that population heterogeneity of transcription factor levels in cells is transmitted unchanged downstream to the target genes. We use a stochastic model of a two-gene cascade with a self-regulating upstream gene to show that, counter to the intuition, there is no simple mapping (bimodal to bimodal, unimodal to unimodal) between the shapes of the distributions of transcription factor numbers and target protein numbers in cells. Due to the presence of the two regulations, the system contains two nonlinear transfer functions, defined by the Hill kinetics of transcription factor binding...
August 23, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28802080/segmental-allotetraploidy-generates-extensive-homeologous-expression-rewiring-and-phenotypic-diversity-at-the-population-level-in-rice
#18
Yue Sun, Ying Wu, Chunwu Yang, Shuai Sun, Xiuyun Lin, Lixia Liu, Chunming Xu, Jonathan F Wendel, Lei Gong, Bao Liu
Allopolyploidization, i.e., concomitant merging and doubling of two or more divergent genomes in a common nucleus/cytoplasm, is known to instantly alter genome-wide transcriptome dynamics, a phenomenon referred to as "transcriptomic shock". However, the immediate effects of transcriptomic alteration in generating phenotypic diversity at the population level remain under-investigated. Here, we employed the MassARRAY-based Sequenom platform to assess and compare orthologous, allelic, and homeologous gene expression status in two tissues (leaf and root) of a set of randomly chosen individuals from populations of parental rice subspecies (indica and japonica), in vitro "hybrids" (parental mixes), reciprocal F1 hybrids and reciprocal tetraploids at the 5(th) -selfed generation (S5)...
August 12, 2017: Molecular Ecology
https://www.readbyqxmd.com/read/28799233/stochastics-of-cellular-differentiation-explained-by-epigenetics-the-case-of-t-cell-differentiation-and-functional-plasticity
#19
REVIEW
Jaydeep Bhat, Johannes Helmuth, Guranda Chitadze, Léonce Kouakanou, Christian Peters, Martin Vingron, Ole Ammerpohl, Dieter Kabelitz
Epigenetic marks including histone modifications and DNA methylation are associated to the regulation of gene expression and activity. In addition, an increasing number of non-coding RNAs with regulatory activity on gene expression have been identified. Alongside, technological advancements allow for the analysis of these mechanisms with high resolution - up to the single-cell level. For instance, the assay for transposase-accessible chromatin using sequencing (ATAC-seq) simultaneously probes for chromatin accessibility and nucleosome positioning...
August 10, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28796841/single-cell-qpcr-reveals-that-additional-hand2-and-microrna-1-facilitate-the-early-reprogramming-progress-of-seven-factor-induced-human-myocytes
#20
Emre Bektik, Adrienne Dennis, Prateek Prasanna, Anant Madabhushi, Ji-Dong Fu
The direct reprogramming of cardiac fibroblasts into induced cardiomyocyte (CM)-like cells (iCMs) holds great promise in restoring heart function. We previously found that human fibroblasts could be reprogrammed toward CM-like cells by 7 reprogramming factors; however, iCM reprogramming in human fibroblasts is both more difficult and more time-intensive than that in mouse cells. In this study, we investigated if additional reprogramming factors could quantitatively and/or qualitatively improve 7-factor-mediated human iCM reprogramming by single-cell quantitative PCR...
2017: PloS One
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