[ { "id": "authors:tgwe9-zwv34", "collection": "authors", "collection_id": "tgwe9-zwv34", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20181126-090207704", "type": "book_section", "title": "Chemical Boltzmann Machines", "book_title": "DNA Computing and Molecular Programming", "author": [ { "family_name": "Poole", "given_name": "William", "clpid": "Poole-W" }, { "family_name": "Ortiz-Mu\u00f1oz", "given_name": "Andr\u00e9s", "orcid": "0000-0003-1824-3230", "clpid": "Ortiz-Mu\u00f1oz-A" }, { "family_name": "Behera", "given_name": "Abhishek", "clpid": "Behera-A" }, { "family_name": "Jones", "given_name": "Nick S.", "clpid": "Jones-N-S" }, { "family_name": "Ouldridge", "given_name": "Thomas E.", "clpid": "Ouldridge-T-E" }, { "family_name": "Winfree", "given_name": "Erik", "orcid": "0000-0002-5899-7523", "clpid": "Winfree-E" }, { "family_name": "Gopalkrishnan", "given_name": "Manoj", "clpid": "Gopalkrishnan-M" } ], "contributor": [ { "family_name": "Brijder", "given_name": "Robert", "clpid": "Brijder-R" }, { "family_name": "Qian", "given_name": "Lulu", "clpid": "Qian-Lulu" } ], "abstract": "How smart can a micron-sized bag of chemicals be? How can an artificial or real cell make inferences about its environment? From which kinds of probability distributions can chemical reaction networks sample? We begin tackling these questions by showing three ways in which a stochastic chemical reaction network can implement a Boltzmann machine, a stochastic neural network model that can generate a wide range of probability distributions and compute conditional probabilities. The resulting models, and the associated theorems, provide a road map for constructing chemical reaction networks that exploit their native stochasticity as a computational resource. Finally, to show the potential of our models, we simulate a chemical Boltzmann machine to classify and generate MNIST digits in-silico.", "doi": "10.1007/978-3-319-66799-7_14", "isbn": "978-3-319-66798-0", "publisher": "Springer", "place_of_publication": "Cham, Switzerland", "publication_date": "2017-08-24", "pages": "210-231" }, { "id": "authors:xp5nf-fxf94", "collection": "authors", "collection_id": "xp5nf-fxf94", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20181126-091545698", "type": "book_section", "title": "Inferring Parameters for an Elementary Step Model of DNA Structure Kinetics with Locally Context-Dependent Arrhenius Rates", "book_title": "DNA Computing and Molecular Programming", "author": [ { "family_name": "Zolaktaf", "given_name": "Sedigheh", "clpid": "Zolaktaf-S" }, { "family_name": "Dannenberg", "given_name": "Frits", "clpid": "Dannenberg-F" }, { "family_name": "Rudelis", "given_name": "Xander", "clpid": "Rudelis-X" }, { "family_name": "Condon", "given_name": "Anne", "clpid": "Condon-A" }, { "family_name": "Schaeffer", "given_name": "Joseph M.", "clpid": "Schaeffer-J-M" }, { "family_name": "Schmidt", "given_name": "Mark", "clpid": "Schmidt-Mark" }, { "family_name": "Thachuk", "given_name": "Chris", "clpid": "Thachuk-C" }, { "family_name": "Winfree", "given_name": "Erik", "orcid": "0000-0002-5899-7523", "clpid": "Winfree-E" } ], "contributor": [ { "family_name": "Brijder", "given_name": "Robert", "clpid": "Brijder-R" }, { "family_name": "Qian", "given_name": "Lulu", "clpid": "Qian-Lulu" } ], "abstract": "Models of nucleic acid thermal stability are calibrated to a wide range of experimental observations, and typically predict equilibrium probabilities of nucleic acid secondary structures with reasonable accuracy. By comparison, a similar calibration and evaluation of nucleic acid kinetic models to a broad range of measurements has not been attempted so far. We introduce an Arrhenius model of interacting nucleic acid kinetics that relates the activation energy of a state transition with the immediate local environment of the affected base pair. Our model can be used in stochastic simulations to estimate kinetic properties and is consistent with existing thermodynamic models. We infer parameters for our model using an ensemble Markov chain Monte Carlo (MCMC) approach on a training dataset with 320 kinetic measurements of hairpin closing and opening, helix association and dissociation, bubble closing and toehold-mediated strand exchange. Our new model surpasses the performance of the previously established Metropolis model both on the training set and on a testing set of size 56 composed of toehold-mediated 3-way strand displacement with mismatches and hairpin opening and closing rates: reaction rates are predicted to within a factor of three for 93.4% and 78.5% of reactions for the training and testing sets, respectively.", "doi": "10.1007/978-3-319-66799-7_12", "isbn": "978-3-319-66798-0", "publisher": "Springer", "place_of_publication": "Cham, Switzerland", "publication_date": "2017-08-24", "pages": "172-187" }, { "id": "authors:1pfn7-t7n80", "collection": "authors", "collection_id": "1pfn7-t7n80", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20181126-085056720", "type": "book_section", "title": "A General-Purpose CRN-to-DSD Compiler with Formal Verification, Optimization, and Simulation Capabilities", "book_title": "DNA Computing and Molecular Programming", "author": [ { "family_name": "Badelt", "given_name": "Stefan", "clpid": "Badelt-S" }, { "family_name": "Shin", "given_name": "Seung Woo", "clpid": "Shin-Seung-Woo" }, { "family_name": "Johnson", "given_name": "Robert F.", "clpid": "Johnson-R-F" }, { "family_name": "Dong", "given_name": "Qing", "clpid": "Dong-Qing" }, { "family_name": "Thachuk", "given_name": "Chris", "clpid": "Thachuk-C" }, { "family_name": "Winfree", "given_name": "Erik", "orcid": "0000-0002-5899-7523", "clpid": "Winfree-E" } ], "contributor": [ { "family_name": "Brijder", "given_name": "Robert", "clpid": "Brijder-R" }, { "family_name": "Qian", "given_name": "Lulu", "clpid": "Qian-Lulu" } ], "abstract": "The mathematical formalism of mass-action chemical reaction networks (CRNs) has been proposed as a mid-level programming language for dynamic molecular systems. Several systematic methods for translating CRNs into domain-level strand displacement (DSD) systems have been developed theoretically, and in some cases demonstrated experimentally. Software that facilitates the simulation of CRNs and DSDs, and that helps automate the construction of DSDs from CRNs, has been instrumental in advancing the field, but as yet has not incorporated the fundamental enabling concept for programming languages and compilers: a rigorous abstraction hierarchy with well-defined semantics at each level, and rigorous correctness proofs establishing the correctness of compilation from a higher level to a lower level. Here, we present a CRN-to-DSD compiler, Nuskell, that makes a first step in this direction. To support the wide range of translation schemes that have already been proposed in the literature, as well as potential new ones that are yet to be proposed, Nuskell provides a domain-specific programming language for translation schemes. A notion of correctness is established on a case-by-case basis using the rate-independent stochastic-level theories of pathway decomposition equivalence and/or CRN bisimulation. The \"best\" DSD implementation for a given CRN can be found by comparing the molecule size, network size, or simulation behavior for a variety of translation schemes. These features are illustrated with a 3-reaction oscillator CRN and a 32-reaction feedforward boolean circuit CRN.", "doi": "10.1007/978-3-319-66799-7_15", "isbn": "978-3-319-66798-0", "publisher": "Springer", "place_of_publication": "Cham, Switzerland", "publication_date": "2017-08-24", "pages": "232-248" }, { "id": "authors:ar1xa-drt87", "collection": "authors", "collection_id": "ar1xa-drt87", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20181126-082746938", "type": "book_section", "title": "Thermodynamic Binding Networks", "book_title": "DNA Computing and Molecular Programming", "author": [ { "family_name": "Doty", "given_name": "David", "orcid": "0000-0002-3922-172X", "clpid": "Doty-D" }, { "family_name": "Rogers", "given_name": "Trent A.", "clpid": "Rogers-T-A" }, { "family_name": "Soloveichik", "given_name": "David", "orcid": "0000-0002-2585-4120", "clpid": "Soloveichik-D" }, { "family_name": "Thachuk", "given_name": "Chris", "clpid": "Thachuk-C" }, { "family_name": "Woods", "given_name": "Damien", "clpid": "Woods-Damien" } ], "contributor": [ { "family_name": "Brijder", "given_name": "Robert", "clpid": "Brijder-R" }, { "family_name": "Qian", "given_name": "Lulu", "clpid": "Qian-Lulu" } ], "abstract": "Strand displacement and tile assembly systems are designed to follow prescribed kinetic rules (i.e., exhibit a specific time-evolution). However, the expected behavior in the limit of infinite time\u2014known as thermodynamic equilibrium\u2014is often incompatible with the desired computation. Basic physical chemistry implicates this inconsistency as a source of unavoidable error. Can the thermodynamic equilibrium be made consistent with the desired computational pathway? In order to formally study this question, we introduce a new model of molecular computing in which computation is driven by the thermodynamic driving forces of enthalpy and entropy. To ensure greatest generality we do not assume that there are any constraints imposed by geometry and treat monomers as unstructured collections of binding sites. In this model we design Boolean AND/OR formulas, as well as a self-assembling binary counter, where the thermodynamically favored states are exactly the desired final output configurations. Though inspired by DNA nanotechnology, the model is sufficiently general to apply to a wide variety of chemical systems.", "doi": "10.1007/978-3-319-66799-7_16", "isbn": "978-3-319-66798-0", "publisher": "Springer", "place_of_publication": "Cham, Switzerland", "publication_date": "2017-08-24", "pages": "249-266" }, { "id": "authors:3ndfz-2t369", "collection": "authors", "collection_id": "3ndfz-2t369", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20181126-091057014", "type": "book_section", "title": "The Design Space of Strand Displacement Cascades with Toehold-Size Clamps", "book_title": "DNA Computing and Molecular Programming", "author": [ { "family_name": "Wang", "given_name": "Boya", "clpid": "Wang-Boya" }, { "family_name": "Thachuk", "given_name": "Chris", "clpid": "Thachuk-C" }, { "family_name": "Ellington", "given_name": "Andrew D.", "clpid": "Ellington-A-D" }, { "family_name": "Soloveichik", "given_name": "David", "orcid": "0000-0002-2585-4120", "clpid": "Soloveichik-D" } ], "contributor": [ { "family_name": "Brijder", "given_name": "Robert", "clpid": "Brijder-R" }, { "family_name": "Qian", "given_name": "Lulu", "clpid": "Qian-Lulu" } ], "abstract": "DNA strand displacement cascades have proven to be a uniquely flexible and programmable primitive for constructing molecular logic circuits, smart structures and devices, and for systems with complex autonomously generated dynamics. Limiting their utility, however, strand displacement systems are susceptible to the spurious release of output even in the absence of the proper combination of inputs\u2014so-called leak. A common mechanism for reducing leak involves clamping the ends of helices to prevent fraying, and thereby kinetically blocking the initiation of undesired displacement. Since a clamp must act as the incumbent toehold for toehold exchange, clamps cannot be stronger than a toehold. In this paper we systematize the properties of the simplest of strand displacement cascades (a translator) with toehold-size clamps. Surprisingly, depending on a few basic parameters, we find a rich and diverse landscape for desired and undesired properties and trade-offs between them. Initial experiments demonstrate a significant reduction of leak.", "doi": "10.1007/978-3-319-66799-7_5", "isbn": "978-3-319-66798-0", "publisher": "Springer", "place_of_publication": "Cham, Switzerland", "publication_date": "2017-08-24", "pages": "64-81" } ]