Mobile DNA最新文献

{"title":"Fast and Robust Strand Displacement Cascades via Systematic Design Strategies","authors":"T. Kennedy, Cadence Pearce, Chris Thachuk","doi":"10.4230/LIPIcs.DNA.28.1","DOIUrl":"https://doi.org/10.4230/LIPIcs.DNA.28.1","url":null,"abstract":"A barrier to wider adoption of molecular computation is the difficulty of implementing arbitrary chemical reaction networks (CRNs) that are robust and replicate the kinetics of designed behavior. DNA Strand Displacement (DSD) cascades have been a favored technology for this purpose due to their potential to emulate arbitrary CRNs and known principles to tune their reaction rates. Progress on leakless cascades has demonstrated that DSDs can be arbitrarily robust to spurious “leak” reactions when incorporating systematic domain level redundancy. These improvements in robustness result in slower kinetics of designed reactions. Existing work has demonstrated the kinetic and thermodynamic effects of sequence mismatch introduction and elimination during displacement. We present a systematic, sequence modification strategy for optimizing the kinetics of leakless cascades without practical cost to their robustness. An in-depth case study explores the effects of this optimization when applied to a typical leakless translator cascade. Thermodynamic analysis of energy barriers and kinetic experimental data support that DSD cascades can be fast and robust.","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"s3-43 1","pages":"1:1-1:17"},"PeriodicalIF":4.9,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90833952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Migrators within migrators: exploring transposable element dynamics in the monarch butterfly, Danaus plexippus","authors":"Tobias Baril, Alex Hayward","doi":"10.1101/2021.09.28.462135","DOIUrl":"https://doi.org/10.1101/2021.09.28.462135","url":null,"abstract":"Lepidoptera (butterflies and moths) are an important model system in ecology and evolution. A high-quality chromosomal genome assembly is available for the monarch butterfly (Danaus plexippus), but it lacks an in-depth transposable element (TE) annotation, presenting an opportunity to explore monarch TE dynamics and the impact of TEs on shaping the monarch genome. We find 6.21% of the monarch genome is comprised of TEs, a reduction of 6.85% compared to the original TE annotation performed on the draft genome assembly. Monarch TE content is low compared to two closely related species with available genomes, Danaus chrysippus (33.97% TE) and Danaus melanippus (11.87% TE). The biggest TE contributions to genome size in the monarch are LINEs and Penelope-like elements, and three newly identified families, r2-hero_dPle (LINE), penelope-1_dPle (Penelope-like), and hase2-1_dPle (SINE), collectively contribute 34.92% of total TE content. We find evidence of recent TE activity, with two novel Tc1 families rapidly expanding over recent timescales (tc1-1_dPle, tc1-2_dPle). LINE fragments show signatures of genomic deletions indicating a high rate of TE turnover. We investigate associations between TEs and wing colouration and immune genes and identify a three-fold increase in TE content around immune genes compared to other host genes. We provide a detailed TE annotation and analysis for the monarch genome, revealing a considerably smaller TE contribution to genome content compared to two closely related Danaus species with available genome assemblies. We identify highly successful novel DNA TE families rapidly expanding over recent timescales, and ongoing signatures of both TE expansion and removal highlight the dynamic nature of repeat content in the monarch genome. Our findings also suggest that insect immune genes are promising candidates for future interrogation of TE-mediated host adaptation.","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"13 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2021-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"62334954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unbiased proteomic mapping of the LINE-1 promoter using CRISPR Cas9.","authors":"Erica M Briggs, Paolo Mita, Xiaoji Sun, Susan Ha, Nikita Vasilyev, Zev R Leopold, Evgeny Nudler, Jef D Boeke, Susan K Logan","doi":"10.1186/s13100-021-00249-9","DOIUrl":"10.1186/s13100-021-00249-9","url":null,"abstract":"<p><strong>Background: </strong>The autonomous retroelement Long Interspersed Element-1 (LINE-1) mobilizes though a copy and paste mechanism using an RNA intermediate (retrotransposition). Throughout human evolution, around 500,000 LINE-1 sequences have accumulated in the genome. Most of these sequences belong to ancestral LINE-1 subfamilies, including L1PA2-L1PA7, and can no longer mobilize. Only a small fraction of LINE-1 sequences, approximately 80 to 100 copies belonging to the L1Hs subfamily, are complete and still capable of retrotransposition. While silenced in most cells, many questions remain regarding LINE-1 dysregulation in cancer cells.</p><p><strong>Results: </strong>Here, we optimized CRISPR Cas9 gRNAs to specifically target the regulatory sequence of the L1Hs 5'UTR promoter. We identified three gRNAs that were more specific to L1Hs, with limited binding to older LINE-1 sequences (L1PA2-L1PA7). We also adapted the C-BERST method (dCas9-APEX2 Biotinylation at genomic Elements by Restricted Spatial Tagging) to identify LINE-1 transcriptional regulators in cancer cells. Our LINE-1 C-BERST screen revealed both known and novel LINE-1 transcriptional regulators, including CTCF, YY1 and DUSP1.</p><p><strong>Conclusion: </strong>Our optimization and evaluation of gRNA specificity and application of the C-BERST method creates a tool for studying the regulatory mechanisms of LINE-1 in cancer. Further, we identified the dual specificity protein phosphatase, DUSP1, as a novel regulator of LINE-1 transcription.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"12 1","pages":"21"},"PeriodicalIF":4.7,"publicationDate":"2021-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9700931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TE Hub: A community-oriented space for sharing and connecting tools, data, resources, and methods for transposable element annotation.","authors":"Tyler A Elliott,&nbsp;Tony Heitkam,&nbsp;Robert Hubley,&nbsp;Hadi Quesneville,&nbsp;Alexander Suh,&nbsp;Travis J Wheeler","doi":"10.1186/s13100-021-00244-0","DOIUrl":"https://doi.org/10.1186/s13100-021-00244-0","url":null,"abstract":"<p><p>Transposable elements (TEs) play powerful and varied evolutionary and functional roles, and are widespread in most eukaryotic genomes. Research into their unique biology has driven the creation of a large collection of databases, software, classification systems, and annotation guidelines. The diversity of available TE-related methods and resources raises compatibility concerns and can be overwhelming to researchers and communicators seeking straightforward guidance or materials. To address these challenges, we have initiated a new resource, TE Hub, that provides a space where members of the TE community can collaborate to document and create resources and methods. The space consists of (1) a website organized with an open wiki framework,  https://tehub.org , (2) a conversation framework via a Twitter account and a Slack channel, and (3) bi-monthly Hub Update video chats on the platform's development. In addition to serving as a centralized repository and communication platform, TE Hub lays the foundation for improved integration, standardization, and effectiveness of diverse tools and protocols. We invite the TE community, both novices and experts in TE identification and analysis, to join us in expanding our community-oriented resource.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"12 1","pages":"16"},"PeriodicalIF":4.9,"publicationDate":"2021-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13100-021-00244-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10338325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Machines from Topological Linkages","authors":"Keenan Breik, Austin Luchsinger, D. Soloveichik","doi":"10.4230/LIPIcs.DNA.27.7","DOIUrl":"https://doi.org/10.4230/LIPIcs.DNA.27.7","url":null,"abstract":"Life is built upon amazingly sophisticated molecular machines whose behavior combines mechanical and chemical action. Engineering of similarly complex nanoscale devices from first principles remains an as yet unrealized goal of bioengineering. In this paper we formalize a simple model of mechanical motion (mechanical linkages) combined with chemical bonding. The model has a natural implementation using DNA with double-stranded rigid links, and single-stranded flexible joints and binding sites. Surprisingly, we show that much of the complex behavior is preserved in an idealized topological model which considers solely the graph connectivity of the linkages. We show a number of artifacts including Boolean logic, catalysts, a fueled motor, and chemo-mechanical coupling, all of which can be understood and reasoned about in the topological model. The variety of achieved behaviors supports the use of topological chemical linkages in understanding and engineering complex molecular behaviors. 2012 ACM Subject Classification Theory of computation → Models of computation; Theory of computation → Computational geometry","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"226 1","pages":"7:1-7:20"},"PeriodicalIF":4.9,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88783620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ENSnano: A 3D Modeling Software for DNA Nanostructures","authors":"N. Lévy, N. Schabanel","doi":"10.4230/LIPIcs.DNA.27.5","DOIUrl":"https://doi.org/10.4230/LIPIcs.DNA.27.5","url":null,"abstract":"7 Since the 1990s, increasingly complex nanostructures have been reliably obtained out of self-assembled 8 DNA strands: from “simple” 2D shapes to 3D gears and articulated nano-objects, and even computing 9 structures. The success of the assembly of these structures relies on a fine tuning of their structure 10 to match the peculiar geometry of DNA helices. Various softwares have been developed to help 11 the designer. These softwares provide essentially four kind of tools: an abstract representation of 12 DNA helices (e.g. cadnano, scadnano, DNApen, 3DNA, Hex-tiles); a 3D view of the design (e.g., 13 vHelix, Adenita, oxDNAviewer); fully automated design (e.g., BScOR, Daedalus, Perdix, Talos, 14 Athena), generally dedicated to a specific kind of design, such as wireframe origami; and coarse grain 15 or thermodynamical physics simulations (e.g., oxDNA, MrDNA, SNUPI, Nupack, ViennaRNA,...). 16 MagicDNA combines some of these approaches to ease the design of configurable DNA origamis. 17 We present our first step in the direction of conciliating all these different approaches and 18 purposes into one single reliable GUI solution: the first fully usable version (design from scratch to 19 export) of our general purpose 3D DNA nanostructure design software ENSnano . We believe that 20 its intuitive, swift and yet powerful graphical interface, combining 2D and 3D editable views, allows 21 fast and precise editing of DNA nanostructures. It also handles editing of large 2D/3D structures 22 smoothly, and imports from the most common solutions. Our software extends the concept of 23 grids introduced in cadnano . Grids allow to abstract and articulated the different parts of a design. 24 ENSnano also provides new design tools which speeds up considerably the design of complex large 3D 25 structures, most notably: a 2D split view , which allows to edit intricate 3D structures which cannot 26 easily be mapped in a 2D view, and a copy, paste & repeat functionality, which takes advantage 27 of the grids to design swiftly large repetitive chunks of a structure. ENSnano has been validated 28 experimentally, as proven by the AFM images of a DNA origami entirely designed in ENSnano . 29 ENSnano is a light-weight ready-to-run independent single-file app, running seamlessly in most of 30 the operating systems (Windows 10, MacOS 10.13+ and Linux). Precompiled versions for Windows 31 and MacOS are ready to download on ENSnano website. As of writing this paper, our software is 32 being actively developed to extend its capacities in various directions discussed in this article. Still, 33 its 3D and 2D editing interface is already meeting our usability goals. Because of its stability and 34 ease of use, we believe that ENSnano could already be integrated in anyone’s design chain, when 35 precise editing of a larger nanostructure is needed.","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"18 1","pages":"5:1-5:23"},"PeriodicalIF":4.9,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74501231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Robust Digital Molecular Design of Binarized Neural Networks","authors":"Johannes Linder, Yuan-Jyue Chen, David Wong, Georg Seelig, L. Ceze, K. Strauss","doi":"10.4230/LIPIcs.DNA.27.1","DOIUrl":"https://doi.org/10.4230/LIPIcs.DNA.27.1","url":null,"abstract":"Molecular programming – a paradigm wherein molecules are engineered to perform computation – shows great potential for applications in nanotechnology, disease diagnostics and smart therapeutics. A key challenge is to identify systematic approaches for compiling abstract models of computation to molecules. Due to their wide applicability, one of the most useful abstractions to realize is neural networks. In prior work, real-valued weights were achieved by individually controlling the concentrations of the corresponding “weight” molecules. However, large-scale preparation of reactants with precise concentrations quickly becomes intractable. Here, we propose to bypass this fundamental problem using Binarized Neural Networks (BNNs), a model that is highly scalable in a molecular setting due to the small number of distinct weight values. We devise a noise-tolerant digital molecular circuit that compactly implements a majority voting operation on binary-valued inputs to compute the neuron output. The network is also rate-independent, meaning the speed at which individual reactions occur does not affect the computation, further increasing robustness to noise. We first demonstrate our design on the MNIST classification task by simulating the system as idealized chemical reactions. Next, we map the reactions to DNA strand displacement cascades, providing simulation results that demonstrate the practical feasibility of our approach. We perform extensive noise tolerance simulations, showing that digital molecular neurons are notably more robust to noise in the concentrations of chemical reactants compared to their analog counterparts. Finally, we provide initial experimental results of a single binarized neuron. Our work suggests a solid framework for building even more complex neural network computation. 2012 ACM Subject Classification Theory of computation → Models of computation; Applied computing","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"14 1","pages":"1:1-1:20"},"PeriodicalIF":4.9,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81810808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reactamole: Functional Reactive Molecular Programming","authors":"T. Klinge, James I. Lathrop, Peter-Michael Osera, Allison Rogers","doi":"10.4230/LIPIcs.DNA.27.10","DOIUrl":"https://doi.org/10.4230/LIPIcs.DNA.27.10","url":null,"abstract":"Chemical reaction networks (CRNs) are an important tool for molecular programming, a field that is rapidly expanding our ability to deploy computer programs into biological systems for a variety of applications. However, CRNs are also difficult to work with due to their massively parallel nature, leading to the need for higher-level languages that allow for easier computation with CRNs. Recently, research has been conducted into a variety of higher-level languages for deterministic CRNs but modeling CRN parallelism, managing error accumulation, and finding natural CRN representations are ongoing challenges. We introduce Reactamole, a higher-level language for deterministic CRNs that utilizes the functional reactive programming (FRP) paradigm to represent CRNs as a reactive dataflow network. Reactamole equates a CRN with a functional reactive program, implementing the key primitives of the FRP paradigm directly as CRNs. The functional nature of Reactamole makes reasoning about molecular programs easier, and its strong static typing allows us to ensure that a CRN is well-formed by virtue of being well-typed. In this paper, we describe the design of Reactamole and how we use CRNs to represent the common datatypes and operations found in FRP. We also demonstrate the potential of this functional reactive approach to molecular programming by giving an extended example where a CRN is constructed using FRP to modulate and demodulate an amplitude modulated signal. 2012 ACM Subject Classification Software and its engineering → Functional languages; Software and its engineering → Data flow languages","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"98 1","pages":"10:1-10:20"},"PeriodicalIF":4.9,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75024415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Directed Non-Cooperative Tile Assembly Is Decidable","authors":"Pierre-Etienne Meunier, Damien Regnault","doi":"10.4230/LIPIcs.DNA.27.6","DOIUrl":"https://doi.org/10.4230/LIPIcs.DNA.27.6","url":null,"abstract":"We provide a complete characterisation of all final states of a model called directed non-cooperative tile self-assembly , also called directed temperature 1 tile assembly , which proves that this model cannot possibly perform Turing computation. This model is a deterministic version of the more general undirected model, whose computational power is still open. Our result uses recent results in the domain, and solves a conjecture formalised in 2011. We believe that this is a major step towards understanding the full model. Temperature 1 tile assembly can be seen as a two-dimensional extension of finite automata, where geometry provides a form of memory and synchronisation, yet the full power of these “geometric blockings” was still largely unknown until recently (note that nontrivial algorithms which are able to build larger structures than the naive constructions have been found).","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"1 1","pages":"6:1-6:21"},"PeriodicalIF":4.9,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89163484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New Ther1-derived SINE Squam3 in scaled reptiles","authors":"N. Vassetzky, S. A. Kosushkin, V. Korchagin, A. Ryskov","doi":"10.21203/rs.3.rs-132339/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-132339/v1","url":null,"abstract":"Background SINEs comprise a significant part of animal genomes and are used to study the evolution of diverse taxa. Despite significant advances in SINE studies in vertebrates and higher eukaryotes in general, their own evolution is poorly understood. Results We have discovered and described in detail a new Squam3 SINE specific for scaled reptiles (Squamata). The subfamilies of this SINE demonstrate different distribution in the genomes of squamates, which together with the data on similar SINEs in the tuatara allowed us to propose a scenario of their evolution in the context of reptilian evolution. Conclusions Ancestral SINEs preserved in small numbers in most genomes can give rise to taxa-specific SINE families. Analysis of this aspect of SINEs can shed light on the history and mechanisms of SINE variation in reptilian genomes.","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"12 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2020-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42350982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}