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https://www.readbyqxmd.com/read/28212112/cancer-as-robust-intrinsic-state-shaped-by-evolution-a-key-issues-review
#1
Ruoshi Yuan, Xiaomei Zhu, Gaowei Wang, Site Li, Ping Ao
Cancer is a complex disease: its pathology cannot be properly understood in terms of independent players-genes, proteins, molecular pathways, or their simple combinations. This is similar to many-body physics of a condensed phase that many important properties are not determined by a single atom or molecule. The rapidly accumulating large 'omics' data also require a new mechanistic and global underpinning to organize for rationalizing cancer complexity. A unifying and quantitative theory was proposed by some of the present authors that cancer is a robust state formed by the endogenous molecular-cellular network, which is evolutionarily built for the developmental processes and physiological functions...
February 17, 2017: Reports on Progress in Physics
https://www.readbyqxmd.com/read/28208380/inferring-hidden-states-in-langevin-dynamics-on-large-networks-average-case-performance
#2
B Bravi, M Opper, P Sollich
We present average performance results for dynamical inference problems in large networks, where a set of nodes is hidden while the time trajectories of the others are observed. Examples of this scenario can occur in signal transduction and gene regulation networks. We focus on the linear stochastic dynamics of continuous variables interacting via random Gaussian couplings of generic symmetry. We analyze the inference error, given by the variance of the posterior distribution over hidden paths, in the thermodynamic limit and as a function of the system parameters and the ratio α between the number of hidden and observed nodes...
January 2017: Physical Review. E
https://www.readbyqxmd.com/read/28208333/stochastic-liouville-equation-for-particles-driven-by-dichotomous-environmental-noise
#3
Paul C Bressloff
We analyze the stochastic dynamics of a large population of noninteracting particles driven by a global environmental input in the form of a dichotomous Markov noise process (DMNP). The population density of particle states evolves according to a stochastic Liouville equation with respect to different realizations of the DMNP. We then exploit the connection with previous work on diffusion in randomly switching environments, in order to derive moment equations for the distribution of solutions to the stochastic Liouville equation...
January 2017: Physical Review. E
https://www.readbyqxmd.com/read/28202515/systematic-in-vivo-inactivation-of-chromatin-regulating-enzymes-identifies-setd2-as-a-potent-tumor-suppressor-in-lung-adenocarcinoma
#4
David M Walter, Olivia S Venancio, Elizabeth L Buza, John W Tobias, Charuhas Deshpande, A Andrea Gudiel, Caroline Kim-Kiselak, Michelle Cicchini, Travis J Yates, David M Feldser
Chromatin modifying genes are frequently mutated in human lung adenocarcinoma, but the functional impact of these mutations on disease initiation and progression is not well understood. Using a CRISPR-based approach, we systematically inactivated three of the most commonly mutated chromatin regulatory genes in two KrasG12D-driven mouse models of lung adenocarcinoma to characterize the impact of their loss. Targeted inactivation of SWI/SNF nucleosome remodeling complex members Smarca4 (Brg1) or Arid1a had complex effects on lung adenocarcinoma initiation and progression...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28196891/insights-into-immune-system-development-and-function-from-mouse-t-cell-repertoires
#5
Zachary Sethna, Yuval Elhanati, Chrissy S Dudgeon, Curtis G Callan, Arnold J Levine, Thierry Mora, Aleksandra M Walczak
The ability of the adaptive immune system to respond to arbitrary pathogens stems from the broad diversity of immune cell surface receptors. This diversity originates in a stochastic DNA editing process (VDJ recombination) that acts on the surface receptor gene each time a new immune cell is created from a stem cell. By analyzing T-cell receptor (TCR) sequence repertoires taken from the blood and thymus of mice of different ages, we quantify the changes in the VDJ recombination process that occur from embryo to young adult...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28182661/representing-high-throughput-expression-profiles-via-perturbation-barcodes-reveals-compound-targets
#6
Tracey M Filzen, Peter S Kutchukian, Jeffrey D Hermes, Jing Li, Matthew Tudor
High throughput mRNA expression profiling can be used to characterize the response of cell culture models to perturbations such as pharmacologic modulators and genetic perturbations. As profiling campaigns expand in scope, it is important to homogenize, summarize, and analyze the resulting data in a manner that captures significant biological signals in spite of various noise sources such as batch effects and stochastic variation. We used the L1000 platform for large-scale profiling of 978 representative genes across thousands of compound treatments...
February 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28180313/stochastic-timing-in-gene-expression-for-simple-regulatory-strategies
#7
Alma Dal Co, Marco Cosentino Lagomarsino, Michele Caselle, Matteo Osella
No abstract text is available yet for this article.
February 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28176840/the-dynamic-mechanism-of-noisy-signal-decoding-in-gene-regulation
#8
Peijiang Liu, Haohua Wang, Lifang Huang, Tianshou Zhou
Experimental evidence supports that signaling pathways can induce different dynamics of transcription factor (TF) activation, but how an input signal is encoded by such a dynamic, noisy TF and further decoded by downstream genes remains largely unclear. Here, using a system of stochastic transcription with signal regulation, we show that (1) keeping the intensity of the signal noise invariant but prolonging the signal duration can both enhance the mutual information (MI) and reduce the energetic cost (EC); (2) if the signal duration is fixed, the larger MI needs the larger EC, but if the signal period is fixed, there is an optimal time that the signal spends at one lower branch, such that MI reaches the maximum; (3) if both the period and the duration are simultaneously fixed, increasing the input noise can always enhance MI in the case of transcription regulation rather than in the case of degradation regulation...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28166778/markov-state-models-of-gene-regulatory-networks
#9
Brian K Chu, Margaret J Tse, Royce R Sato, Elizabeth L Read
BACKGROUND: Gene regulatory networks with dynamics characterized by multiple stable states underlie cell fate-decisions. Quantitative models that can link molecular-level knowledge of gene regulation to a global understanding of network dynamics have the potential to guide cell-reprogramming strategies. Networks are often modeled by the stochastic Chemical Master Equation, but methods for systematic identification of key properties of the global dynamics are currently lacking. RESULTS: The method identifies the number, phenotypes, and lifetimes of long-lived states for a set of common gene regulatory network models...
February 6, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28161395/somatic-clonal-evolution-a-selection-centric-perspective
#10
Jacob Scott, Andriy Marusyk
It is generally accepted that the initiation and progression of cancers is the result of somatic clonal evolution. Despite many peculiarities, evolution within populations of somatic cells should obey the same Darwinian principles as evolution within natural populations, i.e. variability of heritable phenotypes provides the substrate for context-specific selection forces leading to increased population frequencies of phenotypes, which are better adapted to their environment. Yet, within cancer biology, the more prevalent way to view evolution is as being entirely driven by the accumulation of "driver" mutations...
February 1, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28153045/visualizing-phylogenetic-tree-landscapes
#11
James C Wilgenbusch, Wen Huang, Kyle A Gallivan
BACKGROUND: Genomic-scale sequence alignments are increasingly used to infer phylogenies in order to better understand the processes and patterns of evolution. Different partitions within these new alignments (e.g., genes, codon positions, and structural features) often favor hundreds if not thousands of competing phylogenies. Summarizing and comparing phylogenies obtained from multi-source data sets using current consensus tree methods discards valuable information and can disguise potential methodological problems...
February 2, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28143832/isolation-by-distance-and-stochastic-migration-in-a-fragmented-population-of-prosopis-alba
#12
Leandro G Roser, Laura I Ferreyra, Mauricio Ewens, Juan C Vilardi, Beatriz O Saidman
PREMISE OF THE STUDY: Gene flow through dispersal of seeds and pollen is a fundamental determinant of spatial genetic structure (SGS) in natural populations of trees at different spatial scales. Within continuous populations, restrictions to gene flow should be manifested in a process of local genetic differentiation, known as isolation by distance. The present work examines the SGS of a Prosopis alba population in a patchy region where urban, forest, and agricultural areas coexist. The analysis discussed here expands our knowledge about the processes affecting the distribution of the genetic variability in populations of disturbed landscapes...
January 31, 2017: American Journal of Botany
https://www.readbyqxmd.com/read/28137366/somatic-mutations-in-cancer-stochastic-versus-predictable
#13
Barry Gold
The origins of human cancers remain unclear except for a limited number of potent environmental mutagens, such as tobacco and UV light, and in rare cases, familial germ line mutations that affect tumor suppressor genes or oncogenes. A significant component of cancer etiology has been deemed stochastic and correlated with the number of stem cells in a tissue, the number of times the stem cells divide and a low incidence of random DNA polymerase errors that occur during each cell division. While somatic mutations occur during each round of DNA replication, mutations in cancer driver genes are not stochastic...
February 2017: Mutation Research
https://www.readbyqxmd.com/read/28135279/cell-sorting-and-noise-induced-cell-plasticity-coordinate-to-sharpen-boundaries-between-gene-expression-domains
#14
Qixuan Wang, William R Holmes, Julian Sosnik, Thomas Schilling, Qing Nie
A fundamental question in biology is how sharp boundaries of gene expression form precisely in spite of biological variation/noise. Numerous mechanisms position gene expression domains across fields of cells (e.g. morphogens), but how these domains are refined remains unclear. In some cases, domain boundaries sharpen through differential adhesion-mediated cell sorting. However, boundaries can also sharpen through cellular plasticity, with cell fate changes driven by up- or down-regulation of gene expression...
January 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28130236/h-o-ta-estimation-of-dna-methylation-and-hydroxylation-levels-and-efficiencies-from-time-course-data
#15
Charalampos Kyriakopoulos, Pascal Giehr, Verena Wolf
MOTIVATION: Methylation and hydroxylation of cytosines to form 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) belong to the most important epigenetic modifications and their vital role in the regulation of gene expression has been widely recognized. Recent experimental techniques allow to infer methylation and hydroxylation levels at CpG dinucleotides but require a sophisticated statistical analysis to achieve accurate estimates. RESULTS: We present H(O)TA, a software tool based on a stochastic modeling approach, which simultaneously analyzes time course data from hairpin bisulfite sequencing and hairpin oxidative bisulfite sequencing...
January 27, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28128631/suppression-of-beneficial-mutations-in-dynamic-microbial-populations
#16
Philip Bittihn, Jeff Hasty, Lev S Tsimring
Quantitative predictions for the spread of mutations in bacterial populations are essential to interpret evolution experiments and to improve the stability of synthetic gene circuits. We derive analytical expressions for the suppression factor for beneficial mutations in populations that undergo periodic dilutions, covering arbitrary population sizes, dilution factors, and growth advantages in a single stochastic model. We find that the suppression factor grows with the dilution factor and depends nontrivially on the growth advantage, resulting in the preferential elimination of mutations with certain growth advantages...
January 13, 2017: Physical Review Letters
https://www.readbyqxmd.com/read/28127303/reverse-engineering-gene-regulatory-networks-from-measurement-with-missing-values
#17
Oyetunji E Ogundijo, Abdulkadir Elmas, Xiaodong Wang
BACKGROUND: Gene expression time series data are usually in the form of high-dimensional arrays. Unfortunately, the data may sometimes contain missing values: for either the expression values of some genes at some time points or the entire expression values of a single time point or some sets of consecutive time points. This significantly affects the performance of many algorithms for gene expression analysis that take as an input, the complete matrix of gene expression measurement. For instance, previous works have shown that gene regulatory interactions can be estimated from the complete matrix of gene expression measurement...
December 2016: EURASIP Journal on Bioinformatics & Systems Biology
https://www.readbyqxmd.com/read/28118853/allele-specific-analysis-of-cell-fusion-mediated-pluripotent-reprograming-reveals-distinct-and-predictive-susceptibilities-of-human-x-linked-genes-to-reactivation
#18
Irene Cantone, Gopuraja Dharmalingam, Yi-Wah Chan, Anne-Celine Kohler, Boris Lenhard, Matthias Merkenschlager, Amanda G Fisher
BACKGROUND: Inactivation of one X chromosome is established early in female mammalian development and can be reversed in vivo and in vitro when pluripotency factors are re-expressed. The extent of reactivation along the inactive X chromosome (Xi) and the determinants of locus susceptibility are, however, poorly understood. Here we use cell fusion-mediated pluripotent reprograming to study human Xi reactivation and allele-specific single nucleotide polymorphisms (SNPs) to identify reactivated loci...
January 25, 2017: Genome Biology
https://www.readbyqxmd.com/read/28115550/stochastic-gene-expression-bacterial-elites-in-chemotaxis
#19
Simon van Vliet, Martin Ackermann
No abstract text is available yet for this article.
January 23, 2017: Molecular Systems Biology
https://www.readbyqxmd.com/read/28115295/heterochromatin-remodeling-in-embryonic-stem-cells-proceeds-through-stochastic-de-stabilization-of-regional-steady-states
#20
Anastasia Christogianni, Eleftheria Chatzantonaki, Katerina Soupsana, Ioannis Giannios, Aggeliki Platania, Anastasia S Politou, Spyros Georgatos
Cell differentiation is associated with progressive immobilization of chromatin proteins, expansion of heterochromatin, decrease of global transcriptional activity and induction of lineage-specific genes. However, how these processes relate to one another remains unknown. We show here that the heterochromatic domains of mouse embryonic stem cells (ESCs) are dynamically distinct and posesses a mosaic sub-structure. Although random spatio-temporal fluctuations reshuffle continously the chromatin landscape, each heterochromatic territory maintains its dynamic profile, exhibiting robustness and resembling a quasi-steady state...
January 20, 2017: Biochimica et Biophysica Acta
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