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• {"link"=>{"url"=>"http://www.citeulike.org/user/ahsanur/article/10631669"}, "post_time"=>"2012-05-11 01:23:53", "tag"=>"chromatin-regulation", "linkout"=>{"type"=>"DOI", "url"=>"http://dx.doi.org/10.1371/journal.pone.0035703"}, "username"=>"ahsanur", "article_id"=>"10631669"}
• {"link"=>{"url"=>"http://www.citeulike.org/user/TRHvidsten/article/10631669"}, "post_time"=>"2012-05-03 07:30:03", "tag"=>["generalscience", "machinelearning", "systemsbiology"], "linkout"=>{"type"=>"DOI", "url"=>"http://dx.doi.org/10.1371/journal.pone.0035703"}, "username"=>"TRHvidsten", "article_id"=>"10631669"}

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{"title"=>"Chromatin computation", "type"=>"journal", "authors"=>[{"first_name"=>"Barbara", "last_name"=>"Bryant", "scopus_author_id"=>"16202156300"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"doi"=>"10.1371/journal.pone.0035703", "issn"=>"19326203", "sgr"=>"84860451618", "scopus"=>"2-s2.0-84860451618", "pui"=>"364721381", "pmid"=>"22567109", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)"}, "id"=>"64b6855a-dd23-3c81-91d1-cc1e554af24e", "abstract"=>"In living cells, DNA is packaged along with protein and RNA into chromatin. Chemical modifications to nucleotides and histone proteins are added, removed and recognized by multi-functional molecular complexes. Here I define a new computational model, in which chromatin modifications are information units that can be written onto a one-dimensional string of nucleosomes, analogous to the symbols written onto cells of a Turing machine tape, and chromatin-modifying complexes are modeled as read-write rules that operate on a finite set of adjacent nucleosomes. I illustrate the use of this \"chromatin computer\" to solve an instance of the Hamiltonian path problem. I prove that chromatin computers are computationally universal--and therefore more powerful than the logic circuits often used to model transcription factor control of gene expression. Features of biological chromatin provide a rich instruction set for efficient computation of nontrivial algorithms in biological time scales. Modeling chromatin as a computer shifts how we think about chromatin function, suggests new approaches to medical intervention, and lays the groundwork for the engineering of a new class of biological computing machines.", "link"=>"http://www.mendeley.com/research/chromatin-computation", "reader_count"=>50, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>3, "Researcher"=>15, "Student > Ph. D. Student"=>13, "Student > Postgraduate"=>4, "Student > Master"=>4, "Other"=>1, "Student > Bachelor"=>5, "Professor"=>5}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>3, "Researcher"=>15, "Student > Ph. D. Student"=>13, "Student > Postgraduate"=>4, "Student > Master"=>4, "Other"=>1, "Student > Bachelor"=>5, "Professor"=>5}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>7, "Agricultural and Biological Sciences"=>28, "Medicine and Dentistry"=>2, "Neuroscience"=>1, "Physics and Astronomy"=>2, "Chemistry"=>2, "Social Sciences"=>1, "Computer Science"=>7}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Neuroscience"=>{"Neuroscience"=>1}, "Chemistry"=>{"Chemistry"=>2}, "Social Sciences"=>{"Social Sciences"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>28}, "Computer Science"=>{"Computer Science"=>7}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>7}}, "reader_count_by_country"=>{"United States"=>6, "Norway"=>1, "Italy"=>1, "Mexico"=>2, "Chile"=>1, "Germany"=>2}, "group_count"=>1}

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• http://doi.org/10.1016/j.tcs.2015.01.030
• http://doi.org/10.1016/j.jtbi.2013.07.012
• http://doi.org/10.1007/s11047-013-9380-y
• http://doi.org/10.1088/1751-8121/ab0850
• http://doi.org/10.2217/epi.13.9
• http://doi.org/10.1186/s12859-016-1307-z
• http://doi.org/10.1016/j.isci.2019.08.007
• http://doi.org/10.1145/2678280
• http://doi.org/10.1371/journal.pone.0077090
• http://doi.org/10.3390/genes9040201

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• {"type"=>"COMMENT", "annotationUri"=>"info:doi/10.1371/annotation/6105f7a7-ffab-411d-bfb1-79caf68d5c53", "title"=>"Author summary", "body"=>"Methylation of DNA and post-translational modifications to DNA-bound histone proteins influence chromatin structure and gene expression. Specific chemical marks along the genome are read and written by specific protein complexes, in particular chromatin contexts. These context-dependent read/write operations can be thought of as rules that implement a computational program. \n\nI show here that chromatin modification is readily modeled as a massively parallel, random-access, self-modifying stored procedure computer – and that it is computationally universal. Instead of looking for meaning in the individual letters of the histone code, this result suggests that the chromatin modification along the genome at any point is like a snapshot of memory in an ongoing computation, and to understand it we should strive to analyze the program that operates dynamically on chromatin memory.\n\nThe Chromatin Computer (CC) formalism is useful both analytically and synthetically. Analytically, modeling and simulations of chromatin modification using the formalism developed here and the partial knowledge we have of the function of chromatin-modifying complexes can help us develop a deeper understanding of biology. Mathematical study of this model will help us understand evolutionary and biological constraints on the histone modification system. \n\nThe CC can also be used as an abstract model of computation with which to expression algorithms. It may suggest new approaches for in silico computation. I construct a CC program to solve the same Hamiltonian path problem tackled in the first report of creating a computer out of DNA. I implement a simulator of the CC, and run the Hamiltonian path program on it.\n\nWhile there are many engineering hurdles to overcome, it is also tempting to imagine building a real computer out of chromatin and engineered components. \n\nWhile the CC model is simple, it can accommodate many aspects of chromatin biology. In living cells, chromatin interacts with cellular functions in various ways: enzymes remove and place chemical modifications on both histones and DNA; remodeling complexes add, remove and translocate nucleosomes; transcription factors bind specific DNA sequences; signal transduction results in changes in chromatin state; loops form to bring distant parts of chromosomes together; changes in chromatin state result in changes in gene expression, which may feed back to change chromatin state; DNA replication requires chromatin compaction and transfer of chromatin state to daughter cells; RNA processing systems operating on nascent transcripts interact with chromatin, including RNA-directed changes in chromatin state. Most of these interactions can be modeled as read-write processes in the Chromatin Computer. The histone and DNA read/write functions are integral to the basic CC model. The other chromatin-interacting biological processes can be modeled as an expanded “instruction set” of CC read-write rules without altering the key result of universal computability. Rather, the biological instruction set enables efficient computation, allowing living cells to carry out nontrivial computations on a large memory. \n\nThe model presented here lays the groundwork for several mathematical, biological and engineering avenues of investigation. Seeing the chromatin state as a snapshot of an evolving computation may help us understand the biology of chromatin modifiers, many of which are implicated in disease. \n\nI would like to point out a few excellent and relevant papers that have recently come to my attention. Rohlf et al (Epigenomics, in press) review various models of chromatin modification dynamics, and cite two other papers that model chromatin modification as “rewrite” rules. Prohaska et al describe the evolution of chromatin modification writers and readers, and the corresponding shift from a structural to an informational role. They cast chromatin modification in terms of a computing system operating as a set of state transitions, and estimate the size of memory provided by cis-regulatory networks as opposed to chromatin modifications. Benecke describes chromatin modification as a second layer of information on top of the genome, and also estimates memory size.", "isRemoved"=>false, "created"=>"2012-05-03T03:32:29Z", "lastModified"=>"2012-05-03T03:32:29Z", "creator"=>{"userId"=>"173377"}, "highlightedText"=>"", "competingInterestStatement"=>{"creatorWasPrompted"=>true, "hasCompetingInterests"=>true, "body"=>"The author is an employee of Constellation Pharmaceuticals."}, "parentArticle"=>{"doi"=>"info:doi/10.1371/journal.pone.0035703", "state"=>"published", "journals"=>{"PLoSONE"=>{"journalKey"=>"PLoSONE", "eIssn"=>"1932-6203", "title"=>"PLOS ONE"}}}, "replyTreeSize"=>1, "mostRecentActivity"=>"2012-05-03T03:41:14Z", "replies"=>[{"type"=>"REPLY", "parentID"=>49179, "annotationUri"=>"info:doi/10.1371/reply/bd445900-c9c4-40fd-be92-4be007a7e8c0", "title"=>"RE: Author summary", "body"=>"References for author summary:\n\nRohlf et al, \"Modeling the dynamic epigenome: from histone modifications towards self-organizing chromatin,\" Epigenomics. 2012 Apr;4(2):205-19. \n\nProhaska, Stadler and Krakauer, \"Innovation in gene regulation: the case of chromatin computation,\" J Theor Biol. 2010 Jul 7;265(1):27-44.\n\nBenecke, \"Chromatin code, local non-equilibrium dynamics, and the emergence of transcription regulatory programs,\" Eur Phys J E Soft Matter. 2006 Mar;19(3):353-66.", "isRemoved"=>false, "created"=>"2012-05-03T03:41:14Z", "lastModified"=>"2012-05-03T03:41:14Z", "creator"=>{"userId"=>"173377"}, "highlightedText"=>"", "competingInterestStatement"=>{"creatorWasPrompted"=>true, "hasCompetingInterests"=>true, "body"=>"The author is an employee of Constellation Pharmaceuticals"}, "parentArticle"=>{"doi"=>"info:doi/10.1371/journal.pone.0035703", "state"=>"published", "journals"=>{"PLoSONE"=>{"journalKey"=>"PLoSONE", "eIssn"=>"1932-6203", "title"=>"PLOS ONE"}}}, "replyTreeSize"=>0, "mostRecentActivity"=>"2012-05-03T03:41:14Z", "replies"=>[]}]}

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• {"id"=>"224937776460742656", "text"=>"#ISMB #LBR11 Computing with Chromatin Modifications Related Ref: http://t.co/vZP7Z30c", "created_at"=>"2012-07-16T18:45:19Z", "user"=>"WonderMixTape", "user_name"=>"Shannon McWeeney", "user_profile_image"=>"http://a0.twimg.com/profile_images/2396125394/IMG_6294_normal.JPG"}
• {"id"=>"388861611492257792", "text"=>"In living cells, DNA is packaged along with protein and RNA into chromatin http://t.co/wlrE5fJv0f\"", "created_at"=>"2013-10-12T03:00:07Z", "user"=>"thebaybot", "user_name"=>"baybot", "user_profile_image"=>"http://a0.twimg.com/profile_images/378800000263061007/bb2880bd6baf8e5298f42b156c5adebe_normal.jpeg"}
• {"id"=>"464359125745680384", "text"=>"In living cells, DNA is packaged along with protein and RNA into chromatin http://t.co/OXdCuZIjeZ\"", "created_at"=>"2014-05-08T11:00:17Z", "user"=>"thebaybot", "user_name"=>"baybot", "user_profile_image"=>"http://pbs.twimg.com/profile_images/378800000263061007/bb2880bd6baf8e5298f42b156c5adebe_normal.jpeg"}
• {"id"=>"477359803556052992", "text"=>"In living cells, DNA is packaged along with protein and RNA into chromatin http://t.co/A48n8PcHCB\"", "created_at"=>"2014-06-13T08:00:20Z", "user"=>"thebaybot", "user_name"=>"baybot", "user_profile_image"=>"http://pbs.twimg.com/profile_images/378800000263061007/bb2880bd6baf8e5298f42b156c5adebe_normal.jpeg"}
• {"id"=>"489998014749343744", "text"=>"In living cells, DNA is packaged along with protein and RNA into chromatin http://t.co/fZrusbmddp\"", "created_at"=>"2014-07-18T05:00:05Z", "user"=>"thebaybot", "user_name"=>"baybot", "user_profile_image"=>"http://pbs.twimg.com/profile_images/378800000263061007/bb2880bd6baf8e5298f42b156c5adebe_normal.jpeg"}
• {"id"=>"495237592523489280", "text"=>"In living cells, DNA is packaged along with protein and RNA into chromatin http://t.co/ZxVEASR1TW\"", "created_at"=>"2014-08-01T16:00:17Z", "user"=>"thebaybot", "user_name"=>"baybot", "user_profile_image"=>"http://pbs.twimg.com/profile_images/378800000263061007/bb2880bd6baf8e5298f42b156c5adebe_normal.jpeg"}
• {"id"=>"498332955593670656", "text"=>"In living cells, DNA is packaged along with protein and RNA into chromatin http://t.co/ZxVEASR1TW\"", "created_at"=>"2014-08-10T05:00:09Z", "user"=>"thebaybot", "user_name"=>"baybot", "user_profile_image"=>"http://pbs.twimg.com/profile_images/378800000263061007/bb2880bd6baf8e5298f42b156c5adebe_normal.jpeg"}
• {"id"=>"546560728736751616", "text"=>"In living cells, DNA is packaged along with protein and RNA into chromatin http://t.co/ZxVEATpG40\"", "created_at"=>"2014-12-21T07:00:06Z", "user"=>"thebaybot", "user_name"=>"baybot", "user_profile_image"=>"http://pbs.twimg.com/profile_images/378800000263061007/bb2880bd6baf8e5298f42b156c5adebe_normal.jpeg"}
• {"id"=>"561297857316024320", "text"=>"In living cells, DNA is packaged along with protein and RNA into chromatin http://t.co/70Cl0Xlt1c\"", "created_at"=>"2015-01-30T23:00:12Z", "user"=>"thebaybot", "user_name"=>"baybot", "user_profile_image"=>"http://pbs.twimg.com/profile_images/378800000263061007/bb2880bd6baf8e5298f42b156c5adebe_normal.jpeg"}
• {"id"=>"618479631805624320", "text"=>"In living cells, DNA is packaged along with protein and RNA into chromatin http://t.co/ZxVEAT84VW\" #computing", "created_at"=>"2015-07-07T18:00:09Z", "user"=>"thebaybot", "user_name"=>"baybot", "user_profile_image"=>"http://pbs.twimg.com/profile_images/378800000263061007/bb2880bd6baf8e5298f42b156c5adebe_normal.jpeg"}
• {"id"=>"622299842891640832", "text"=>"In living cells, DNA is packaged along with protein and RNA into chromatin http://t.co/ZxVEAT84VW\" #computer", "created_at"=>"2015-07-18T07:00:18Z", "user"=>"thebaybot", "user_name"=>"baybot", "user_profile_image"=>"http://pbs.twimg.com/profile_images/378800000263061007/bb2880bd6baf8e5298f42b156c5adebe_normal.jpeg"}
• {"id"=>"632552372712161280", "text"=>"In living cells, DNA is packaged along with protein and RNA into chromatin http://t.co/ZxVEAT84VW\" #computer", "created_at"=>"2015-08-15T14:00:12Z", "user"=>"thebaybot", "user_name"=>"baybot", "user_profile_image"=>"http://pbs.twimg.com/profile_images/378800000263061007/bb2880bd6baf8e5298f42b156c5adebe_normal.jpeg"}

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Figshare

• {"files"=>["https://ndownloader.figshare.com/files/644817"], "description"=>"<p>Figure from Adleman 1994 (5). In the pictured directed graph, there is a unique Hamiltonian path from vertex 0 to vertex 6: 0123456.</p>", "links"=>[], "tags"=>["genetics and genomics", "Computational biology", "computer science", "mathematics"], "article_id"=>315309, "categories"=>["Information And Computing Sciences", "Mathematics", "Biological Sciences", "Genetics"], "users"=>["Barbara Bryant"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0035703.g002", "stats"=>{"downloads"=>2, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Hamiltonian_path_problem_/315309", "title"=>"Hamiltonian path problem.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-05-02 01:28:29"}
• {"files"=>["https://ndownloader.figshare.com/files/644869"], "description"=>"<p>(A) Application of a rule to the starting configuration. The chromatin tape is shown as a set of 7 nucleosomes, each with 6 writable positions. The top row shows the initial tape configuration; the bottom row shows the configuration after the application of the rule 0***** B*****------ 1-----. The leftmost position in each nucleosomes maps to a numbered vertex in the graph. The remaining 5 positions are used to determine whether each node appears exactly once in the path. This rule extends the path from 0 to 1. (B) Two path-checking rules operating sequentially on an intermediate configuration in the computation. (C) The final chromatin configuration showing the successful solution.</p>", "links"=>[], "tags"=>["chromatin", "solving", "hamiltonian"], "article_id"=>315369, "categories"=>["Information And Computing Sciences", "Mathematics", "Biological Sciences", "Genetics"], "users"=>["Barbara Bryant"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0035703.g003", "stats"=>{"downloads"=>3, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Operation_of_a_chromatin_computer_solving_the_Hamiltonian_Path_Problem_/315369", "title"=>"Operation of a chromatin computer solving the Hamiltonian Path Problem.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-05-02 01:29:29"}
• {"files"=>["https://ndownloader.figshare.com/files/644780"], "description"=>"<p>This diagram illustrates the operation of the rule XX** BB**---- XX--. The chromatin tape is composed of nucleosomes having four writable locations. Each location can be marked with the symbol B or X. Rules in this CC operate on two adjacent nucleosomes. In the illustration of the read portion of the rule, matching to any symbol (*) is shown with an empty. An empty square in the write portion of the rule leaves the current symbol unchanged (−).</p>", "links"=>[], "tags"=>["chromatin"], "article_id"=>315277, "categories"=>["Information And Computing Sciences", "Mathematics", "Biological Sciences", "Genetics"], "users"=>["Barbara Bryant"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0035703.g001", "stats"=>{"downloads"=>1, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Example_of_the_operation_of_a_chromatin_computer_rule_/315277", "title"=>"Example of the operation of a chromatin computer rule.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-05-02 01:27:57"}
• {"files"=>["https://ndownloader.figshare.com/files/644937"], "description"=>"<p>(A) Turing machine finite state machine with three rules that rewrite the string “xy” to “zz”. (B) The corresponding chromatin computer. The first position in each 3-position nucleosome corresponds to the location of the Turing read/write head. The second position corresponds to the state of the Turing machine. The third position corresponds to a cell on the Turing tape.</p>", "links"=>[], "tags"=>["turing", "chromatin"], "article_id"=>315434, "categories"=>["Information And Computing Sciences", "Mathematics", "Biological Sciences", "Genetics"], "users"=>["Barbara Bryant"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0035703.g004", "stats"=>{"downloads"=>1, "page_views"=>65, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mapping_from_a_Turing_machine_to_a_chromatin_computer_/315434", "title"=>"Mapping from a Turing machine to a chromatin computer.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-05-02 01:30:34"}
• {"files"=>["https://ndownloader.figshare.com/files/331866"], "description"=>"<div><p>In living cells, DNA is packaged along with protein and RNA into chromatin. Chemical modifications to nucleotides and histone proteins are added, removed and recognized by multi-functional molecular complexes. Here I define a new computational model, in which chromatin modifications are information units that can be written onto a one-dimensional string of nucleosomes, analogous to the symbols written onto cells of a Turing machine tape, and chromatin-modifying complexes are modeled as read-write rules that operate on a finite set of adjacent nucleosomes. I illustrate the use of this “chromatin computer” to solve an instance of the Hamiltonian path problem. I prove that chromatin computers are computationally universal – and therefore more powerful than the logic circuits often used to model transcription factor control of gene expression. Features of biological chromatin provide a rich instruction set for efficient computation of nontrivial algorithms in biological time scales. Modeling chromatin as a computer shifts how we think about chromatin function, suggests new approaches to medical intervention, and lays the groundwork for the engineering of a new class of biological computing machines.</p> </div>", "links"=>[], "tags"=>["chromatin", "computation"], "article_id"=>125535, "categories"=>["Information And Computing Sciences", "Mathematics", "Biological Sciences", "Genetics"], "users"=>["Barbara Bryant"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0035703", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Chromatin_Computation/125535", "title"=>"Chromatin Computation", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-05-02 01:32:15"}
• {"files"=>["https://ndownloader.figshare.com/files/644995"], "description"=>"<p>Biological equivalents for computational concepts in the CC model.</p>", "links"=>[], "tags"=>["equivalents", "computational", "concepts", "cc"], "article_id"=>315487, "categories"=>["Information And Computing Sciences", "Mathematics", "Biological Sciences", "Genetics"], "users"=>["Barbara Bryant"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0035703.t001", "stats"=>{"downloads"=>0, "page_views"=>35, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Biological_equivalents_for_computational_concepts_in_the_CC_model_/315487", "title"=>"Biological equivalents for computational concepts in the CC model.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-05-02 01:31:27"}

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Relative Metric

{"start_date"=>"2012-01-01T00:00:00Z", "end_date"=>"2012-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences/Cell biology", "average_usage"=>[319, 556, 679, 785, 881, 970, 1062, 1149, 1236, 1323, 1402, 1474, 1545, 1617, 1681, 1754, 1822, 1892, 1963, 2031, 2099, 2165, 2233, 2299, 2359]}, {"subject_area"=>"/Computer and information sciences", "average_usage"=>[352, 587, 696, 809, 901, 989, 1072, 1156, 1257, 1334, 1422, 1486, 1555, 1647, 1714, 1780, 1844, 1919, 1997, 2051, 2138, 2198, 2267, 2324, 2391]}]}

F1000Prime