Cell cycle time series gene expression data encoded as cyclic attractors in Hopfield systems
Publication Date
November 17, 2017
Journal
PLOS Computational Biology
Authors
Anthony Szedlak, Spencer Sims, Nicholas Smith, Giovanni Paternostro, et al
Volume
13
Issue
11
Pages
e1005849
DOI
https://dx.plos.org/10.1371/journal.pcbi.1005849
Publisher URL
http://journals.plos.org/ploscompbiol/article?id=10.1371%2Fjournal.pcbi.1005849
Scopus
85036574663
Mendeley
http://www.mendeley.com/research/cell-cycle-time-series-gene-expression-data-encoded-cyclic-attractors-hopfield-systems
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Mendeley | Further Information

{"title"=>"Cell cycle time series gene expression data encoded as cyclic attractors in Hopfield systems", "type"=>"journal", "authors"=>[{"first_name"=>"Anthony", "last_name"=>"Szedlak", "scopus_author_id"=>"42262887200"}, {"first_name"=>"Spencer", "last_name"=>"Sims", "scopus_author_id"=>"57198421615"}, {"first_name"=>"Nicholas", "last_name"=>"Smith", "scopus_author_id"=>"57199117430"}, {"first_name"=>"Giovanni", "last_name"=>"Paternostro", "scopus_author_id"=>"6603149480"}, {"first_name"=>"Carlo", "last_name"=>"Piermarocchi", "scopus_author_id"=>"7004112373"}], "year"=>2017, "source"=>"PLoS Computational Biology", "identifiers"=>{"pui"=>"619520709", "sgr"=>"85036574663", "issn"=>"15537358", "arxiv"=>"1707.07707", "scopus"=>"2-s2.0-85036574663", "doi"=>"10.1371/journal.pcbi.1005849", "isbn"=>"1111111111"}, "id"=>"29006ee1-1a58-37b1-a53e-fc2766c3ee62", "abstract"=>"Modern time series gene expression and other omics data sets have enabled unprecedented resolution of the dynamics of cellular processes such as cell cycle and response to pharmaceutical compounds. In anticipation of the proliferation of time series data sets in the near future, we use the Hopfield model, a recurrent neural network based on spin glasses, to model the dynamics of cell cycle in HeLa (human cervical cancer) and S. cerevisiae cells. We study some of the rich dynamical properties of these cyclic Hopfield systems, including the ability of populations of simulated cells to recreate experimental expression data and the effects of noise on the dynamics. Next, we use a genetic algorithm to identify sets of genes which, when selectively inhibited by local external fields representing gene silencing compounds such as kinase inhibitors, disrupt the encoded cell cycle. We find, for example, that inhibiting the set of four kinases BRD4, MAPK1, NEK7, and YES1 in HeLa cells causes simulated cells to accumulate in the M phase. Finally, we suggest possible improvements and extensions to our model. Author Summary Cell cycle – the process in which a parent cell replicates its DNA and divides into two daughter cells – is an upregulated process in many forms of cancer. Identifying gene inhibition targets to regulate cell cycle is important to the development of effective therapies. Although modern high throughput techniques offer unprecedented resolution of the molecular details of biological processes like cell cycle, analyzing the vast quantities of the resulting experimental data and extracting actionable information remains a formidable task. Here, we create a dynamical model of the process of cell cycle using the Hopfield model (a type of recurrent neural network) and gene expression data from human cervical cancer cells and yeast cells. We find that the model recreates the oscillations observed in experimental data. Tuning the level of noise (representing the inherent randomness in gene expression and regulation) to the \" edge of chaos \" is crucial for the proper behavior of the system. We then use this model to identify potential gene targets for disrupting the process of cell cycle. This method could be applied to other time series data sets and used to predict the effects of untested targeted perturbations.", "link"=>"http://www.mendeley.com/research/cell-cycle-time-series-gene-expression-data-encoded-cyclic-attractors-hopfield-systems", "reader_count"=>13, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>4, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>1, "Student > Master"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>4, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>1, "Student > Master"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>4, "Mathematics"=>2, "Agricultural and Biological Sciences"=>3, "Physics and Astronomy"=>1}, "reader_count_by_subdiscipline"=>{"Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>3}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Mathematics"=>{"Mathematics"=>2}, "Unspecified"=>{"Unspecified"=>3}}, "group_count"=>3}

Scopus | Further Information

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