Mobile DNAPub Date : 2023-01-01DOI: 10.4230/LIPIcs.DNA.29.4
Joseph Don Berleant
{"title":"Rational Design of DNA Sequences with Non-Orthogonal Binding Interactions","authors":"Joseph Don Berleant","doi":"10.4230/LIPIcs.DNA.29.4","DOIUrl":"https://doi.org/10.4230/LIPIcs.DNA.29.4","url":null,"abstract":"Molecular computation involving promiscuous, or non-orthogonal, binding interactions between system components is found commonly in natural biological systems, as well as some proposed human-made molecular computers. Such systems are characterized by the fact that each computational unit, such as a domain within a DNA strand, may bind to several different partners with distinct, prescribed binding strengths. Unfortunately, implementing systems of molecular computation that incorporate non-orthogonal binding is difficult, because researchers lack a robust, general-purpose method for designing molecules with this type of behavior. In this work, we describe and demonstrate a process for the rational design of DNA sequences with prescribed non-orthogonal binding behavior. This process makes use of a model that represents large sets of non-orthogonal DNA sequences using fixed-length binary strings, and estimates the differential binding affinity between pairs of sequences through the Hamming distance between their corresponding binary strings. The real-world applicability of this model is supported by simulations and some experimental data. We then select two previously described systems of molecular computation involving non-orthogonal interactions, and apply our sequence design process to implement them using DNA strand displacement. Our simulated results on these two systems demonstrate both digital and analog computation. We hope that this work motivates the development and implementation of new computational paradigms based on non-orthogonal binding.","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"44 1","pages":"4:1-4:22"},"PeriodicalIF":4.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74261429","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}
Mobile DNAPub Date : 2023-01-01DOI: 10.4230/LIPIcs.DNA.29.5
Jordan Lovrod, Boyan Beronov, Chenwei Zhang, Erik Winfree, Anne Condon
{"title":"Revisiting Hybridization Kinetics with Improved Elementary Step Simulation","authors":"Jordan Lovrod, Boyan Beronov, Chenwei Zhang, Erik Winfree, Anne Condon","doi":"10.4230/LIPIcs.DNA.29.5","DOIUrl":"https://doi.org/10.4230/LIPIcs.DNA.29.5","url":null,"abstract":"Nucleic acid strands, which react by forming and breaking Watson-Crick base pairs, can be designed to form complex nanoscale structures or devices. Controlling such systems requires accurate predictions of the reaction rate and of the folding pathways of interacting strands. Simulators such as Multistrand model these kinetic properties using continuous-time Markov chains (CTMCs), whose states and transitions correspond to secondary structures and elementary base pair changes, respectively. The transient dynamics of a CTMC are determined by a kinetic model, which assigns transition rates to pairs of states, and the rate of a reaction can be estimated using the mean first passage time (MFPT) of its CTMC. However, use of Multistrand is limited by its slow runtime, particularly on rare events, and the quality of its rate predictions is compromised by a poorly-calibrated and simplistic kinetic model. The former limitation can be addressed by constructing truncated CTMCs, which only include a small subset of states and transitions, selected either manually or through simulation. As a first step to address the latter limitation, Bayesian posterior inference in an Arrhenius-type kinetic model was performed in earlier work, using a small experimental dataset of DNA reaction rates and a fixed set of manually truncated CTMCs, which we refer to as Assumed Pathway (AP) state spaces. In this work we extend this approach, by introducing a new prior model that is directly motivated by the physical meaning of the parameters and that is compatible with experimental measurements of elementary rates, and by using a larger dataset of 1105 reactions as well as larger truncated state spaces obtained from the recently introduced stochastic Pathway Elaboration (PE) method. We assess the quality of the resulting posterior distribution over kinetic parameters, as well as the quality of the posterior reaction rates predicted using AP and PE state spaces. Finally, we use the newly parameterised PE state spaces and Multistrand simulations to investigate the strong variation of helix hybridization reaction rates in a dataset of Hata et al. While we find strong evidence for the nucleation-zippering model of hybridization, in the classical sense that the rate-limiting phase is composed of elementary steps reaching a small “nucleus” of critical stability, the strongly sequence-dependent structure of the trajectory ensemble up to nucleation appears to be much richer than assumed in the model by Hata et al. In particular, rather than being dominated by the collision probability of nucleation sites, the trajectory segment between first binding and nucleation tends to visit numerous secondary structures involving misnucleation and hairpins, and has a sizeable effect on the probability of overcoming the nucleation barrier.","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"103 1","pages":"5:1-5:24"},"PeriodicalIF":4.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80372422","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}
Mobile DNAPub Date : 2023-01-01DOI: 10.4230/LIPIcs.DNA.29.1
Ahmed Shalaby, Chris Thachuk, Damien Woods
{"title":"Minimum Free Energy, Partition Function and Kinetics Simulation Algorithms for a Multistranded Scaffolded DNA Computer","authors":"Ahmed Shalaby, Chris Thachuk, Damien Woods","doi":"10.4230/LIPIcs.DNA.29.1","DOIUrl":"https://doi.org/10.4230/LIPIcs.DNA.29.1","url":null,"abstract":"","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"9 1","pages":"1:1-1:22"},"PeriodicalIF":4.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74565617","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}
Mobile DNAPub Date : 2022-12-28DOI: 10.1186/s13100-022-00286-y
Mobile Dna Editorial Board
{"title":"Obituary: Haig Kazazian and Horizontal Transfer (1937 - 2022).","authors":"Mobile Dna Editorial Board","doi":"10.1186/s13100-022-00286-y","DOIUrl":"https://doi.org/10.1186/s13100-022-00286-y","url":null,"abstract":"","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"13 1","pages":"32"},"PeriodicalIF":4.9,"publicationDate":"2022-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9795599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10456924","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}
Mobile DNAPub Date : 2022-12-03DOI: 10.1186/s13100-022-00288-w
Héléna Vassilieff, Sana Haddad, Véronique Jamilloux, Nathalie Choisne, Vikas Sharma, Delphine Giraud, Mariène Wan, Saad Serfraz, Andrew D W Geering, Pierre-Yves Teycheney, Florian Maumus
{"title":"CAULIFINDER: a pipeline for the automated detection and annotation of caulimovirid endogenous viral elements in plant genomes.","authors":"Héléna Vassilieff, Sana Haddad, Véronique Jamilloux, Nathalie Choisne, Vikas Sharma, Delphine Giraud, Mariène Wan, Saad Serfraz, Andrew D W Geering, Pierre-Yves Teycheney, Florian Maumus","doi":"10.1186/s13100-022-00288-w","DOIUrl":"https://doi.org/10.1186/s13100-022-00288-w","url":null,"abstract":"<p><p>Plant, animal and protist genomes often contain endogenous viral elements (EVEs), which correspond to partial and sometimes entire viral genomes that have been captured in the genome of their host organism through a variety of integration mechanisms. While the number of sequenced eukaryotic genomes is rapidly increasing, the annotation and characterization of EVEs remains largely overlooked. EVEs that derive from members of the family Caulimoviridae are widespread across tracheophyte plants, and sometimes they occur in very high copy numbers. However, existing programs for annotating repetitive DNA elements in plant genomes are poor at identifying and then classifying these EVEs. Other than accurately annotating plant genomes, there is intrinsic value in a tool that could identify caulimovirid EVEs as they testify to recent or ancient host-virus interactions and provide valuable insights into virus evolution. In response to this research need, we have developed CAULIFINDER, an automated and sensitive annotation software package. CAULIFINDER consists of two complementary workflows, one to reconstruct, annotate and group caulimovirid EVEs in a given plant genome and the second to classify these genetic elements into officially recognized or tentative genera in the Caulimoviridae. We have benchmarked the CAULIFINDER package using the Vitis vinifera reference genome, which contains a rich assortment of caulimovirid EVEs that have previously been characterized using manual methods. The CAULIFINDER package is distributed in the form of a Docker image.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"13 1","pages":"31"},"PeriodicalIF":4.9,"publicationDate":"2022-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9719215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10687183","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}
Mobile DNAPub Date : 2022-12-02DOI: 10.1186/s13100-022-00287-x
Simanti Das, Amanda E Jones, John M Abrams
{"title":"Generalized nuclear localization of retroelement transcripts.","authors":"Simanti Das, Amanda E Jones, John M Abrams","doi":"10.1186/s13100-022-00287-x","DOIUrl":"10.1186/s13100-022-00287-x","url":null,"abstract":"<p><strong>Background: </strong>LINE-1s, Alus and SVAs are the only retrotransposition competent elements in humans. Their mobilization followed by insertional mutagenesis is often linked to disease. Apart from these rare integration events, accumulation of retrotransposition intermediates in the cytoplasm is potentially pathogenic due to induction of inflammatory response pathways. Although the retrotransposition of LINE-1 and Alu retroelements has been studied in considerable detail, there are mixed observations about the localization of their RNAs.</p><p><strong>Results: </strong>We undertook a comprehensive and unbiased approach to analyze retroelement RNA localization using common cell lines and publicly available datasets containing RNA-sequencing data from subcellular fractions. Using our customized analytic pipeline, we compared localization patterns of RNAs transcribed from retroelements and single-copy protein coding genes. Our results demonstrate a generalized characteristic pattern of retroelement RNA nuclear localization that is conserved across retroelement classes as well as evolutionarily young and ancient elements. Preferential nuclear enrichment of retroelement transcripts was consistently observed in cell lines, in vivo and across species. Moreover, retroelement RNA localization patterns were dynamic and subject to change during development, as seen in zebrafish embryos.</p><p><strong>Conclusion: </strong>The pronounced nuclear localization of transcripts arising from ancient as well as de novo transcribed retroelements suggests that these transcripts are retained in the nucleus as opposed to being re-imported to the nucleus or degraded in the cytoplasm. This raises the possibility that there is adaptive value associated with this localization pattern to the host, the retroelements or possibly both.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"13 1","pages":"30"},"PeriodicalIF":4.9,"publicationDate":"2022-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9717504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10333142","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}
Mobile DNAPub Date : 2022-11-30DOI: 10.1186/s13100-022-00285-z
Michelle Almeida da Paz, Leila Taher
{"title":"T3E: a tool for characterising the epigenetic profile of transposable elements using ChIP-seq data.","authors":"Michelle Almeida da Paz, Leila Taher","doi":"10.1186/s13100-022-00285-z","DOIUrl":"10.1186/s13100-022-00285-z","url":null,"abstract":"<p><strong>Background: </strong>Despite the advent of Chromatin Immunoprecipitation Sequencing (ChIP-seq) having revolutionised our understanding of the mammalian genome's regulatory landscape, many challenges remain. In particular, because of their repetitive nature, the sequencing reads derived from transposable elements (TEs) pose a real bioinformatics challenge, to the point that standard analysis pipelines typically ignore reads whose genomic origin cannot be unambiguously ascertained.</p><p><strong>Results: </strong>We show that discarding ambiguously mapping reads may lead to a systematic underestimation of the number of reads associated with young TE families/subfamilies. We also provide evidence suggesting that the strategy of randomly permuting the location of the read mappings (or the TEs) that is often used to compute the background for enrichment calculations at TE families/subfamilies can result in both false positive and negative enrichments. To address these problems, we present the Transposable Element Enrichment Estimator (T3E), a tool that makes use of ChIP-seq data to characterise the epigenetic profile of associated TE families/subfamilies. T3E weights the number of read mappings assigned to the individual TE copies of a family/subfamily by the overall number of genomic loci to which the corresponding reads map, and this is done at the single nucleotide level. In addition, T3E computes ChIP-seq enrichment relative to a background estimated based on the distribution of the read mappings in the input control DNA. We demonstrated the capabilities of T3E on 23 different ChIP-seq libraries. T3E identified enrichments that were consistent with previous studies. Furthermore, T3E detected context-specific enrichments that are likely to pinpoint unexplored TE families/subfamilies with individual TE copies that have been frequently exapted as cis-regulatory elements during the evolution of mammalian regulatory networks.</p><p><strong>Conclusions: </strong>T3E is a novel open-source computational tool (available for use at: https://github.com/michelleapaz/T3E ) that overcomes some of the pitfalls associated with the analysis of ChIP-seq data arising from the repetitive mammalian genome and provides a framework to shed light on the epigenetics of entire TE families/subfamilies.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"13 1","pages":"29"},"PeriodicalIF":4.9,"publicationDate":"2022-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9710123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10333093","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}
Mobile DNAPub Date : 2022-11-30DOI: 10.1186/s13100-022-00282-2
Dragomira N Markova, Fatema B Ruma, Claudio Casola, Ayda Mirsalehi, Esther Betrán
{"title":"Recurrent co-domestication of PIF/Harbinger transposable element proteins in insects.","authors":"Dragomira N Markova, Fatema B Ruma, Claudio Casola, Ayda Mirsalehi, Esther Betrán","doi":"10.1186/s13100-022-00282-2","DOIUrl":"https://doi.org/10.1186/s13100-022-00282-2","url":null,"abstract":"<p><strong>Background: </strong>Transposable elements (TEs) are selfish DNA sequences capable of moving and amplifying at the expense of host cells. Despite this, an increasing number of studies have revealed that TE proteins are important contributors to the emergence of novel host proteins through molecular domestication. We previously described seven transposase-derived domesticated genes from the PIF/Harbinger DNA family of TEs in Drosophila and a co-domestication. All PIF TEs known in plants and animals distinguish themselves from other DNA transposons by the presence of two genes. We hypothesize that there should often be co-domestications of the two genes from the same TE because the transposase (gene 1) has been described to be translocated to the nucleus by the MADF protein (gene 2). To provide support for this model of new gene origination, we investigated available insect species genomes for additional evidence of PIF TE domestication events and explored the co-domestication of the MADF protein from the same TE insertion.</p><p><strong>Results: </strong>After the extensive insect species genomes exploration of hits to PIF transposases and analyses of their context and evolution, we present evidence of at least six independent PIF transposable elements proteins domestication events in insects: two co-domestications of both transposase and MADF proteins in Anopheles (Diptera), one transposase-only domestication event and one co-domestication in butterflies and moths (Lepidoptera), and two transposases-only domestication events in cockroaches (Blattodea). The predicted nuclear localization signals for many of those proteins and dicistronic transcription in some instances support the functional associations of co-domesticated transposase and MADF proteins.</p><p><strong>Conclusions: </strong>Our results add to a co-domestication that we previously described in fruit fly genomes and support that new gene origination through domestication of a PIF transposase is frequently accompanied by the co-domestication of a cognate MADF protein in insects, potentially for regulatory functions. We propose a detailed model that predicts that PIF TE protein co-domestication should often occur from the same PIF TE insertion.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"13 1","pages":"28"},"PeriodicalIF":4.9,"publicationDate":"2022-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9710019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10678217","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}
Mobile DNAPub Date : 2022-06-13DOI: 10.1186/s13100-022-00274-2
Koo, Hyunjin, Kim, Soomin, Park, Hyun-Seung, Lee, Sang-Ji, Paek, Nam-Chon, Cho, Jungnam, Yang, Tae-Jin
{"title":"Amplification of LTRs of extrachromosomal linear DNAs (ALE-seq) identifies two active Oryco LTR retrotransposons in the rice cultivar Dongjin","authors":"Koo, Hyunjin, Kim, Soomin, Park, Hyun-Seung, Lee, Sang-Ji, Paek, Nam-Chon, Cho, Jungnam, Yang, Tae-Jin","doi":"10.1186/s13100-022-00274-2","DOIUrl":"https://doi.org/10.1186/s13100-022-00274-2","url":null,"abstract":"Long terminal repeat retrotransposons (LTR-RTs) make up a considerable portion of plant genomes. New insertions of these active LTR-RTs modify gene structures and functions and play an important role in genome evolution. Therefore, identifying active forms of LTR-RTs could uncover the effects of these elements in plants. Extrachromosomal linear DNA (eclDNA) forms during LTR-RT replication; therefore, amplification LTRs of eclDNAs followed by sequencing (ALE-seq) uncover the current transpositional potential of the LTR-RTs. The ALE-seq protocol was validated by identification of Tos17 in callus of Nipponbare cultivar. Here, we identified two active LTR-RTs belonging to the Oryco family on chromosomes 6 and 9 in rice cultivar Dongjin callus based on the ALE-seq technology. Each Oryco family member has paired LTRs with identical sequences and internal domain regions. Comparison of the two LTR-RTs revealed 97% sequence identity in their internal domains and 65% sequence identity in their LTRs. These two putatively active Oryco LTR-RT family members could be used to expand our knowledge of retrotransposition mechanisms and the effects of LTR-RTs on the rice genome.","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"29 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2022-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138518116","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}
Mobile DNAPub Date : 2022-06-08DOI: 10.1186/s13100-022-00273-3
Juan Paolo A. Sicat, Paul Visendi, Steven O. Sewe, S. Bouvaine, S. Seal
{"title":"Correction: Characterization of transposable elements within the Bemisia tabaci species complex","authors":"Juan Paolo A. Sicat, Paul Visendi, Steven O. Sewe, S. Bouvaine, S. Seal","doi":"10.1186/s13100-022-00273-3","DOIUrl":"https://doi.org/10.1186/s13100-022-00273-3","url":null,"abstract":"","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2022-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44901530","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}