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Beyond Cancer Stem Cells: Understanding Cancer Heterogeneity Through Gene Regulatory Networks and Single Cell Analysis

Ivan Gomez
2013 Journal of Stem Cell Research & Therapy  
Here we provide intuitive thinking with systems biology view to explain the inevitable heterogeneity of cancer cells as an abnormal cell type driven by dynamics of gene regulatory network.  ...  Mutational clonal evolution and cancer stem cell models could only partially explain the ubiquitous heterogeneous tumour cell population.  ...  The regulatory interactions now impose heavy constraints on how the expression levels of individual genes can change, as a consequence, it maps mathematically in the highly constrained way in which the  ... 
doi:10.4172/2157-7633.s7-002 fatcat:r2ddwescgfgpblq4phuv3aznqi

From genotypes to organisms: State-of-the-art and perspectives of a cornerstone in evolutionary dynamics [article]

Susanna Manrubia, José A. Cuesta, Jacobo Aguirre, Sebastian E. Ahnert, Lee Altenberg, Alejandro V. Cano, Pablo Catalán, Ramon Diaz-Uriarte, Santiago F. Elena, Juan Antonio García-Martín, Paulien Hogeweg, Bhavin S. Khatri (+6 others)
2021 arXiv   pre-print
Understanding how genotypes map onto phenotypes, fitness, and eventually organisms is arguably the next major missing piece in a fully predictive theory of evolution.  ...  Though we are still far from achieving a complete picture of these relationships, our current understanding of simpler questions, such as the structure induced in the space of genotypes by sequences mapped  ...  Challenges in the computation of realistic genotypephenotype maps", which took place in Zaragoza (March 13th to March 15th, 2019) and triggered the production of this work.  ... 
arXiv:2002.00363v3 fatcat:iuqhuiwfczaqvjmadssrcm35ru

From genotypes to organisms: State-of-the-art and perspectives of a cornerstone in evolutionary dynamics

Susanna Manrubia, José A. Cuesta, Jacobo Aguirre, Sebastian E. Ahnert, Lee Altenberg, Alejandro V. Cano, Pablo Catalán, Ramon Diaz-Uriarte, Santiago F. Elena, Juan Antonio García-Martín, Paulien Hogeweg, Bhavin S. Khatri (+6 others)
2021 Physics of Life Reviews  
Understanding how genotypes map onto phenotypes, fitness, and eventually organisms is arguably the next major missing piece in a fully predictive theory of evolution.  ...  Though we are still far from achieving a complete picture of these relationships, our current understanding of simpler questions, such as the structure induced in the space of genotypes by sequences mapped  ...  Challenges in the computation of realistic genotypephenotype maps", which took place in Zaragoza (March 13th to March 15th, 2019) and triggered the production of this work.  ... 
doi:10.1016/j.plrev.2021.03.004 pmid:34088608 fatcat:kdgh5d2g2bgclcluvbp5jndm3q

Aligning functional network constraint to evolutionary outcomes [article]

Katharina Wollenberg Valero
2018 bioRxiv   pre-print
number of protein interactions within a cell (gene pleiotropy) determines the fitness effect of mutations.  ...  Genomic architecture, which describes how all gene products interact, has been discussed to be another dimension of functional genetic constraint.  ...  Furthermore, proteins with many interactants may be constrained in the evolution of their functional sites to instances of co-evolution with the interactant genes, in order to maintain their functionality  ... 
doi:10.1101/278663 fatcat:ztbla6z2cfhddnklrz3cb4nvya

A unified formal framework for developmental andevolutionary change in gene regulatory network models [article]

Enrico Borriello, Sara I. Walker, Manfred D. Laubichler
2019 arXiv   pre-print
Evolution, by contrast entails genotypic change through the acquisition/loss of genes and changes in the network topology of interactions among genes.  ...  We show how the realization of specific phenotypes can be controlled by gene duplication events (used here as an archetypal evolutionary event able to change the genotype), and how successive events of  ...  Different models of mutation could be assumed, which in turn determine the minimum numbers of replicas the cell needs to acquire in order to change from one type to another.  ... 
arXiv:1809.02331v2 fatcat:nfs5aq4cqjgkvmmsnwacarrce4

Evolutionary Dynamics in Gene Networks and Inference Algorithms

Daniel Aguilar-Hidalgo, María Lemos, Antonio Córdoba
2015 Computation  
Gene regulatory networks (GRNs) are directed networks that define interactions (links) among different genes/proteins involved in such processes.  ...  How the GRN modifies its topology, to properly drive a developmental process, and how this regulation was acquired across evolution are questions that the evolutionary dynamics of gene networks tackles  ...  Dynamical rules and stochastic perturbations define the trajectories in the state space and determine their final states.  ... 
doi:10.3390/computation3010099 fatcat:f7el6e5wf5gdjdmn74buifmb7u

Optimal Constrained Stationary Intervention in Gene Regulatory Networks

Babak Faryabi, Golnaz Vahedi, Jean-Francois Chamberland, Aniruddha Datta, Edward R. Dougherty
2008 EURASIP Journal on Bioinformatics and Systems Biology  
A key objective of gene network modeling is to develop intervention strategies to alter regulatory dynamics in such a way as to reduce the likelihood of undesirable phenotypes.  ...  Optimal stationary intervention policies have been developed for gene regulation in the framework of probabilistic Boolean networks in a number of settings.  ...  Acknowledgments This work was supported in part by the National Science Foundation (ECS-0355227, CCF-0514644, and ECCS-0701531), the National Cancer Institute (R01 CA-104620 and CA-90301), and the Translational  ... 
doi:10.1155/2008/620767 pmid:18516276 pmcid:PMC3171398 fatcat:5psfaisshngfrb3rsbxtj4dzqi

Mathematical and Computational Modeling in Complex Biological Systems

Zhiwei Ji, Ke Yan, Wenyang Li, Haigen Hu, Xiaoliang Zhu
2017 BioMed Research International  
The use of computational models in systems biology allows us to explore the pathogenesis of complex diseases, improve our understanding of the latent molecular mechanisms, and promote treatment strategy  ...  The biological process and molecular functions involved in the cancer progression remain difficult to understand for biologists and clinical doctors.  ...  This study was also supported by the Foundation of Talent's Startup Project in Zhejiang Gongshang University (no. 1120XJ2116016).  ... 
doi:10.1155/2017/5958321 pmid:28386558 pmcid:PMC5366773 fatcat:e6pyjhqdyzfllk6q2l5yjzssf4

Eukaryotic gene regulation in three dimensions and its impact on genome evolution

M Madan Babu, Sarath Chandra Janga, Ines de Santiago, Ana Pombo
2008 Current Opinion in Genetics and Development  
This improved understanding of gene regulation also raises fundamental questions about how spatial features might have constrained the organization of genes on eukaryotic chromosomes and how mutations  ...  In this review, we discuss recent studies that highlight the role of spatial components in gene regulation and their impact on genome evolution.  ...  nuclear space to be coordinated in space and time, this raises a fundamental question: have the spatial processes involved in gene regulation constrained genome evolution?  ... 
doi:10.1016/j.gde.2008.10.002 pmid:19007886 fatcat:vhl5n6yuzrdonjcmrxvogisq5y

What and How Do Cancer Systems Biologists Explain?

Anya Plutynski, Marta Bertolaso
2018 Philosophy of Science  
in patterns of vulnerability to cancer.  ...  Second, we argue that some explanations in systems biology of cancer are concerned with properties of signaling networks (such as robustness or fragility) and how they may play an important causal role  ...  The particular architecture of the network determines how movement through the state space is constrained.  ... 
doi:10.1086/699716 fatcat:4vnfomo2xjhrja7ipf4ftg4xse

ncDNA and drift drive binding site accumulation

Troy Ruths, Luay Nakhleh
2012 BMC Evolutionary Biology  
To test this hypothesis, we devised a genome-based regulatory pathway model and subjected it to the forces of evolution through population genetic simulations.  ...  The amount of transcription factor binding sites (TFBS) in an organism's genome positively correlates with the complexity of the regulatory network of the organism.  ...  Acknowledgements This work was supported in part by an NSF GRFP and a DOE/Krell CSGF to TR and an NSF grant CCF-0622037 and an Alfred P Sloan Research Fellowship to LN The contents are solely the responsibility  ... 
doi:10.1186/1471-2148-12-159 pmid:22935101 pmcid:PMC3556125 fatcat:xxe6kagrh5aexbt3bkpfe6dmdu

Fourth International Biannual Evolution and Cancer Conference (Resistance, resilience, and robustness: Can we target cancer's evolutionary and ecological nature?)

Benjamin Roche, Beata Ujvari, Frédéric Thomas
2018 Evolutionary Applications  
By determining the order of genes along and among chromosomes, the genome organizes the gene interaction map accordingly; (ii) different coding patterns contribute to different types of cancer evolution  ...  uses, and partitioning MoAs in space or time so as to segregate their use as much as practically possible.  ...  Pierre Martinez (Cancer Research Center of Lyon, Lyon, France) on the evolution of Barrett's esophagus (BE) through space and time at single-crypt and whole-biopsy levels.  ... 
doi:10.1111/eva.12616 pmcid:PMC5999206 fatcat:n6quyxshc5aqtg5odhbpusl2hm

Understanding Biological Regulation Through Synthetic Biology

Caleb J. Bashor, James J. Collins
2018 Annual Review of Biophysics  
Here we outline research that uses the process of gene circuit engineering to advance biological discovery.  ...  As we discuss, using circuit engineering to predictively reorganize, rewire, and reconstruct cellular regulation serves as the ultimate means of testing and understanding how cellular phenotype emerges  ...  using synthetic circuits to study how noise is propagated within a gene networks (82) and sources of contributions to noise in gene regulation (90) .  ... 
doi:10.1146/annurev-biophys-070816-033903 pmid:29547341 fatcat:tj6bjg7nirebjkfppjdkzhtjku

Neutral space analysis for a Boolean network model of the fission yeast cell cycle network

Gonzalo A Ruz, Tania Timmermann, Javiera Barrera, Eric Goles
2014 Biological Research  
In this paper, we explore the neutral space of a Schizosaccharomyces pombe (fission yeast) cell cycle network through an evolution strategy to generate a neutral graph, composed of Boolean regulatory networks  ...  to cancer in animals or a directed regulation could be applied for biotechnological processes using yeast.  ...  Acknowledgements The authors would like to thank CONICYT-Chile under grant Fondecyt 11110088 (GAR), Fondecyt 1140090 (EG), CONICYT Doctoral scholarship (TT), and ANILLO ACT-88, for financially supporting  ... 
doi:10.1186/0717-6287-47-64 pmid:25723815 pmcid:PMC4335775 fatcat:tu4ne7s4ibezzisfbjn22ivhie

Evolutionary dynamics and information hierarchies in biological systems

Sara Imari Walker, Benjamin J. Callahan, Gaurav Arya, J. David Barry, Tanmoy Bhattacharya, Sergei Grigoryev, Matteo Pellegrini, Karsten Rippe, Susan M. Rosenberg
2013 Annals of the New York Academy of Sciences  
as a passive filter selecting for random changes at the nucleotide level with a paradigm in which evolution is a dynamic process both constrained and driven by the informational architecture of organisms  ...  Current research spanning and uniting diverse fields and exploring the physical and chemical nature of organisms across temporal, spatial, and organizational scales is replacing the model of evolution  ...  The authors wish to thank the hospitality of the Aspen Center for Physics for hosting the workshop, which was supported in part by the National Science Foundation under Grant no. PHY-1066293.  ... 
doi:10.1111/nyas.12140 pmid:23691975 fatcat:fjsffnec6rfevlgtbd2thyrqau
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