NAR Genomics and Bioinformatics最新文献

筛选
英文 中文
Detecting co-selection through excess linkage disequilibrium in bacterial genomes. 通过细菌基因组中过多的连锁不平衡检测共同选择。
IF 4.6
NAR Genomics and Bioinformatics Pub Date : 2024-06-06 eCollection Date: 2024-06-01 DOI: 10.1093/nargab/lqae061
Sudaraka Mallawaarachchi, Gerry Tonkin-Hill, Anna K Pöntinen, Jessica K Calland, Rebecca A Gladstone, Sergio Arredondo-Alonso, Neil MacAlasdair, Harry A Thorpe, Janetta Top, Samuel K Sheppard, David Balding, Nicholas J Croucher, Jukka Corander
{"title":"Detecting co-selection through excess linkage disequilibrium in bacterial genomes.","authors":"Sudaraka Mallawaarachchi, Gerry Tonkin-Hill, Anna K Pöntinen, Jessica K Calland, Rebecca A Gladstone, Sergio Arredondo-Alonso, Neil MacAlasdair, Harry A Thorpe, Janetta Top, Samuel K Sheppard, David Balding, Nicholas J Croucher, Jukka Corander","doi":"10.1093/nargab/lqae061","DOIUrl":"10.1093/nargab/lqae061","url":null,"abstract":"<p><p>Population genomics has revolutionized our ability to study bacterial evolution by enabling data-driven discovery of the genetic architecture of trait variation. Genome-wide association studies (GWAS) have more recently become accompanied by genome-wide epistasis and co-selection (GWES) analysis, which offers a phenotype-free approach to generating hypotheses about selective processes that simultaneously impact multiple loci across the genome. However, existing GWES methods only consider associations between distant pairs of loci within the genome due to the strong impact of linkage-disequilibrium (LD) over short distances. Based on the general functional organisation of genomes it is nevertheless expected that majority of co-selection and epistasis will act within relatively short genomic proximity, on co-variation occurring within genes and their promoter regions, and within operons. Here, we introduce LDWeaver, which enables an exhaustive GWES across both short- and long-range LD, to disentangle likely neutral co-variation from selection. We demonstrate the ability of LDWeaver to efficiently generate hypotheses about co-selection using large genomic surveys of multiple major human bacterial pathogen species and validate several findings using functional annotation and phenotypic measurements. Our approach will facilitate the study of bacterial evolution in the light of rapidly expanding population genomic data.</p>","PeriodicalId":33994,"journal":{"name":"NAR Genomics and Bioinformatics","volume":"6 2","pages":"lqae061"},"PeriodicalIF":4.6,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11155488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141284890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
From RNA sequence to its three-dimensional structure: geometrical structure, stability and dynamics of selected fragments of SARS-CoV-2 RNA. 从 RNA 序列到其三维结构:SARS-CoV-2 RNA 某些片段的几何结构、稳定性和动力学。
IF 4.6
NAR Genomics and Bioinformatics Pub Date : 2024-06-04 eCollection Date: 2024-06-01 DOI: 10.1093/nargab/lqae062
Leonid Gorb, Ivan Voiteshenko, Vasyl Hurmach, Margarita Zarudnaya, Alex Nyporko, Tetiana Shyryna, Maksym Platonov, Szczepan Roszak, Bakhtiyor Rasulev
{"title":"From RNA sequence to its three-dimensional structure: geometrical structure, stability and dynamics of selected fragments of SARS-CoV-2 RNA.","authors":"Leonid Gorb, Ivan Voiteshenko, Vasyl Hurmach, Margarita Zarudnaya, Alex Nyporko, Tetiana Shyryna, Maksym Platonov, Szczepan Roszak, Bakhtiyor Rasulev","doi":"10.1093/nargab/lqae062","DOIUrl":"10.1093/nargab/lqae062","url":null,"abstract":"<p><p>In this computational study, we explore the folding of a particular sequence using various computational tools to produce two-dimensional structures, which are then transformed into three-dimensional structures. We then study the geometry, energetics and dynamics of these structures using full electron quantum-chemical and classical molecular dynamics calculations. Our study focuses on the SARS-CoV-2 RNA fragment GGaGGaGGuguugcaGG and its various structures, including a G-quadruplex and five different hairpins. We examine the impact of two types of counterions (K<sup>+</sup> and Na<sup>+</sup>) and flanking nucleotides on their geometrical characteristics, relative stability and dynamic properties. Our results show that the G-quadruplex structure is the most stable among the constructed hairpins. We confirm its topological stability through molecular dynamics simulations. Furthermore, we observe that the nucleotide loop consisting of seven nucleotides is the most flexible part of the RNA fragment. Additionally, we find that RNA networks of intermolecular hydrogen bonds are highly sensitive to the surrounding environment. Our findings reveal the loss of 79 old hydrogen bonds and the formation of 91 new ones in the case when the G-quadruplex containing flanking nucleotides is additionally stabilized by Na<sup>+</sup> counterions.</p>","PeriodicalId":33994,"journal":{"name":"NAR Genomics and Bioinformatics","volume":"6 2","pages":"lqae062"},"PeriodicalIF":4.6,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11148665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141248869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
G-quadruplex propensity in H. neanderthalensis, H. sapiens and Denisovans mitochondrial genomes. 尼安德特人、智人和丹尼索瓦人线粒体基因组中的 G-四叠体倾向。
IF 4.6
NAR Genomics and Bioinformatics Pub Date : 2024-05-30 eCollection Date: 2024-06-01 DOI: 10.1093/nargab/lqae060
Václav Brázda, Lucie Šislerová, Anne Cucchiarini, Jean-Louis Mergny
{"title":"G-quadruplex propensity in <i>H. neanderthalensis</i>, <i>H. sapiens</i> and Denisovans mitochondrial genomes.","authors":"Václav Brázda, Lucie Šislerová, Anne Cucchiarini, Jean-Louis Mergny","doi":"10.1093/nargab/lqae060","DOIUrl":"10.1093/nargab/lqae060","url":null,"abstract":"<p><p>Current methods of processing archaeological samples combined with advances in sequencing methods lead to disclosure of a large part of <i>H. neanderthalensis</i> and Denisovans genetic information. It is hardly surprising that the genome variability between modern humans, Denisovans and <i>H. neanderthalensis</i> is relatively limited. Genomic studies may provide insight on the metabolism of extinct human species or lineages. Detailed analysis of G-quadruplex sequences in <i>H. neanderthalensis</i> and Denisovans mitochondrial DNA showed us interesting features. Relatively similar patterns in mitochondrial DNA are found compared to modern humans, with one notable exception for <i>H. neanderthalensis</i>. An interesting difference between <i>H. neanderthalensis</i> and <i>H. sapiens</i> corresponds to a motif found in the D-loop region of mtDNA, which is responsible for mitochondrial DNA replication. This area is directly responsible for the number of mitochondria and consequently for the efficient energy metabolism of cell<i>. H. neanderthalensis</i> harbor a long uninterrupted run of guanines in this region, which may cause problems for replication, in contrast with <i>H. sapiens</i>, for which this run is generally shorter and interrupted. One may propose that the predominant <i>H. sapiens</i> motif provided a selective advantage for modern humans regarding mtDNA replication and function.</p>","PeriodicalId":33994,"journal":{"name":"NAR Genomics and Bioinformatics","volume":"6 2","pages":"lqae060"},"PeriodicalIF":4.6,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11137754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141180982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Advances in single-cell long-read sequencing technologies. 单细胞长线程测序技术的进展。
IF 4
NAR Genomics and Bioinformatics Pub Date : 2024-05-20 eCollection Date: 2024-06-01 DOI: 10.1093/nargab/lqae047
Pallavi Gupta, Hannah O'Neill, Ernst J Wolvetang, Aniruddha Chatterjee, Ishaan Gupta
{"title":"Advances in single-cell long-read sequencing technologies.","authors":"Pallavi Gupta, Hannah O'Neill, Ernst J Wolvetang, Aniruddha Chatterjee, Ishaan Gupta","doi":"10.1093/nargab/lqae047","DOIUrl":"10.1093/nargab/lqae047","url":null,"abstract":"<p><p>With an increase in accuracy and throughput of long-read sequencing technologies, they are rapidly being assimilated into the single-cell sequencing pipelines. For transcriptome sequencing, these techniques provide RNA isoform-level information in addition to the gene expression profiles. Long-read sequencing technologies not only help in uncovering complex patterns of cell-type specific splicing, but also offer unprecedented insights into the origin of cellular complexity and thus potentially new avenues for drug development. Additionally, single-cell long-read DNA sequencing enables high-quality assemblies, structural variant detection, haplotype phasing, resolving high-complexity regions, and characterization of epigenetic modifications. Given that significant progress has primarily occurred in single-cell RNA isoform sequencing (scRiso-seq), this review will delve into these advancements in depth and highlight the practical considerations and operational challenges, particularly pertaining to downstream analysis. We also aim to offer a concise introduction to complementary technologies for single-cell sequencing of the genome, epigenome and epitranscriptome. We conclude by identifying certain key areas of innovation that may drive these technologies further and foster more widespread application in biomedical science.</p>","PeriodicalId":33994,"journal":{"name":"NAR Genomics and Bioinformatics","volume":"6 2","pages":"lqae047"},"PeriodicalIF":4.0,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11106032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141076780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Nanopore Current Events Magnifier (nanoCEM): a novel tool for visualizing current events at modification sites of nanopore sequencing. 纳米孔电流事件放大镜(nanoCEM):纳米孔测序修饰位点电流事件可视化的新型工具。
IF 4
NAR Genomics and Bioinformatics Pub Date : 2024-05-20 eCollection Date: 2024-06-01 DOI: 10.1093/nargab/lqae052
Zhihao Guo, Ying Ni, Lu Tan, Yanwen Shao, Lianwei Ye, Sheng Chen, Runsheng Li
{"title":"Nanopore Current Events Magnifier (nanoCEM): a novel tool for visualizing current events at modification sites of nanopore sequencing.","authors":"Zhihao Guo, Ying Ni, Lu Tan, Yanwen Shao, Lianwei Ye, Sheng Chen, Runsheng Li","doi":"10.1093/nargab/lqae052","DOIUrl":"10.1093/nargab/lqae052","url":null,"abstract":"<p><p>Nanopore sequencing technologies have enabled the direct detection of base modifications in DNA or RNA molecules. Despite these advancements, the tools for visualizing electrical current, essential for analyzing base modifications, are often lacking in clarity and compatibility with diverse nanopore pipelines. Here, we present Nanopore Current Events Magnifier (nanoCEM, https://github.com/lrslab/nanoCEM), a Python command-line tool designed to facilitate the identification of DNA/RNA modification sites through enhanced visualization and statistical analysis. Compatible with the four preprocessing methods including 'f5c resquiggle', 'f5c eventalign', 'Tombo' and 'move table', nanoCEM is applicable to RNA and DNA analysis across multiple flow cell types. By utilizing rescaling techniques and calculating various statistical features, nanoCEM provides more accurate and comparable visualization of current events, allowing researchers to effectively observe differences between samples and showcase the modified sites.</p>","PeriodicalId":33994,"journal":{"name":"NAR Genomics and Bioinformatics","volume":"6 2","pages":"lqae052"},"PeriodicalIF":4.0,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11106030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141076808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
BaRDIC: robust peak calling for RNA-DNA interaction data. BaRDIC:RNA-DNA 相互作用数据的稳健峰值调用。
IF 4
NAR Genomics and Bioinformatics Pub Date : 2024-05-20 eCollection Date: 2024-06-01 DOI: 10.1093/nargab/lqae054
Dmitry E Mylarshchikov, Arina I Nikolskaya, Olesja D Bogomaz, Anastasia A Zharikova, Andrey A Mironov
{"title":"BaRDIC: robust peak calling for RNA-DNA interaction data.","authors":"Dmitry E Mylarshchikov, Arina I Nikolskaya, Olesja D Bogomaz, Anastasia A Zharikova, Andrey A Mironov","doi":"10.1093/nargab/lqae054","DOIUrl":"10.1093/nargab/lqae054","url":null,"abstract":"<p><p>Chromatin-associated non-coding RNAs play important roles in various cellular processes by targeting genomic loci. Two types of genome-wide NGS experiments exist to detect such targets: 'one-to-al', which focuses on targets of a single RNA, and 'all-to-al', which captures targets of all RNAs in a sample. As with many NGS experiments, they are prone to biases and noise, so it becomes essential to detect 'peaks'-specific interactions of an RNA with genomic targets. Here, we present BaRDIC-Binomial RNA-DNA Interaction Caller-a tailored method to detect peaks in both types of RNA-DNA interaction data. BaRDIC is the first tool to simultaneously take into account the two most prominent biases in the data: chromatin heterogeneity and distance-dependent decay of interaction frequency. Since RNAs differ in their interaction preferences, BaRDIC adapts peak sizes according to the abundances and contact patterns of individual RNAs. These features enable BaRDIC to make more robust predictions than currently applied peak-calling algorithms and better handle the characteristic sparsity of all-to-all data. The BaRDIC package is freely available at https://github.com/dmitrymyl/BaRDIC.</p>","PeriodicalId":33994,"journal":{"name":"NAR Genomics and Bioinformatics","volume":"6 2","pages":"lqae054"},"PeriodicalIF":4.0,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11106031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141076783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The determinants of the rarity of nucleic and peptide short sequences in nature. 自然界中核酸和肽短序列稀有性的决定因素。
IF 5.4
NAR Genomics and Bioinformatics Pub Date : 2024-04-04 eCollection Date: 2024-06-01 DOI: 10.1093/nargab/lqae029
Nikol Chantzi, Manvita Mareboina, Maxwell A Konnaris, Austin Montgomery, Michail Patsakis, Ioannis Mouratidis, Ilias Georgakopoulos-Soares
{"title":"The determinants of the rarity of nucleic and peptide short sequences in nature.","authors":"Nikol Chantzi, Manvita Mareboina, Maxwell A Konnaris, Austin Montgomery, Michail Patsakis, Ioannis Mouratidis, Ilias Georgakopoulos-Soares","doi":"10.1093/nargab/lqae029","DOIUrl":"10.1093/nargab/lqae029","url":null,"abstract":"<p><p>The prevalence of nucleic and peptide short sequences across organismal genomes and proteomes has not been thoroughly investigated. We examined 45 785 reference genomes and 21 871 reference proteomes, spanning archaea, bacteria, eukaryotes and viruses to calculate the rarity of short sequences in them. To capture this, we developed a metric of the rarity of each sequence in nature, the rarity index. We find that the frequency of certain dipeptides in rare oligopeptide sequences is hundreds of times lower than expected, which is not the case for any dinucleotides. We also generate predictive regression models that infer the rarity of nucleic and proteomic sequences across nature or within each domain of life and viruses separately. When examining each of the three domains of life and viruses separately, the <i>R</i>² performance of the model predicting rarity for 5-mer peptides from mono- and dipeptides ranged between 0.814 and 0.932. A separate model predicting rarity for 10-mer oligonucleotides from mono- and dinucleotides achieved <i>R</i>² performance between 0.408 and 0.606. Our results indicate that the mono- and dinucleotide composition of nucleic sequences and the mono- and dipeptide composition of peptide sequences can explain a significant proportion of the variance in their frequencies in nature.</p>","PeriodicalId":33994,"journal":{"name":"NAR Genomics and Bioinformatics","volume":"6 2","pages":"lqae029"},"PeriodicalIF":5.4,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10993293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140872441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Evolutionary and functional insights into the Ski2-like helicase family in Archaea: a comparison of Thermococcales ASH-Ski2 and Hel308 activities. 古菌中 Ski2 样螺旋酶家族的进化和功能研究:热球菌 ASH-Ski2 和 Hel308 活性的比较。
IF 4.6
NAR Genomics and Bioinformatics Pub Date : 2024-03-18 eCollection Date: 2024-03-01 DOI: 10.1093/nargab/lqae026
Manon Batista, Petra Langendijk-Genevaux, Marta Kwapisz, Isabelle Canal, Duy Khanh Phung, Laura Plassart, Régine Capeyrou, Yann Moalic, Mohamed Jebbar, Didier Flament, Gwennaele Fichant, Marie Bouvier, Béatrice Clouet-d'Orval
{"title":"Evolutionary and functional insights into the Ski2-like helicase family in Archaea: a comparison of Thermococcales ASH-Ski2 and Hel308 activities.","authors":"Manon Batista, Petra Langendijk-Genevaux, Marta Kwapisz, Isabelle Canal, Duy Khanh Phung, Laura Plassart, Régine Capeyrou, Yann Moalic, Mohamed Jebbar, Didier Flament, Gwennaele Fichant, Marie Bouvier, Béatrice Clouet-d'Orval","doi":"10.1093/nargab/lqae026","DOIUrl":"10.1093/nargab/lqae026","url":null,"abstract":"<p><p>RNA helicases perform essential housekeeping and regulatory functions in all domains of life by binding and unwinding RNA molecules. The Ski2-like proteins are primordial helicases that play an active role in eukaryotic RNA homeostasis pathways, with multiple homologs having specialized functions. The significance of the expansion and diversity of Ski2-like proteins in Archaea, the third domain of life, has not yet been established. Here, by studying the phylogenetic diversity of Ski2-like helicases among archaeal genomes and the enzymatic activities of those in Thermococcales, we provide further evidence of the function of this protein family in archaeal metabolism of nucleic acids. We show that, in the course of evolution, ASH-Ski2 and Hel308-Ski2, the two main groups of Ski2-like proteins, have diverged in their biological functions. Whereas Hel308 has been shown to mainly act on DNA, we show that ASH-Ski2, previously described to be associated with the 5'-3' aRNase J exonuclease, acts on RNA by supporting an efficient annealing activity, but also an RNA unwinding with a 3'-5' polarity. To gain insights into the function of Ski2, we also analyse the transcriptome of <i>Thermococcus barophilus</i> ΔASH-Ski2 mutant strain and provide evidence of the importance of ASH-Ski2 in cellular metabolism pathways related to translation.</p>","PeriodicalId":33994,"journal":{"name":"NAR Genomics and Bioinformatics","volume":"6 1","pages":"lqae026"},"PeriodicalIF":4.6,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10946056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140159212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
mRNAid, an open-source platform for therapeutic mRNA design and optimization strategies. mRNAid,一个用于治疗 mRNA 设计和优化策略的开源平台。
IF 4.6
NAR Genomics and Bioinformatics Pub Date : 2024-03-12 eCollection Date: 2024-03-01 DOI: 10.1093/nargab/lqae028
Nikita Vostrosablin, Shuhui Lim, Pooja Gopal, Kveta Brazdilova, Sushmita Parajuli, Xiaona Wei, Anna Gromek, David Prihoda, Martin Spale, Anja Muzdalo, Jamie Greig, Constance Yeo, Joanna Wardyn, Petr Mejzlik, Brian Henry, Anthony W Partridge, Danny A Bitton
{"title":"mRNAid, an open-source platform for therapeutic mRNA design and optimization strategies.","authors":"Nikita Vostrosablin, Shuhui Lim, Pooja Gopal, Kveta Brazdilova, Sushmita Parajuli, Xiaona Wei, Anna Gromek, David Prihoda, Martin Spale, Anja Muzdalo, Jamie Greig, Constance Yeo, Joanna Wardyn, Petr Mejzlik, Brian Henry, Anthony W Partridge, Danny A Bitton","doi":"10.1093/nargab/lqae028","DOIUrl":"10.1093/nargab/lqae028","url":null,"abstract":"<p><p>Recent COVID-19 vaccines unleashed the potential of mRNA-based therapeutics. A common bottleneck across mRNA-based therapeutic approaches is the rapid design of mRNA sequences that are translationally efficient, long-lived and non-immunogenic. Currently, an accessible software tool to aid in the design of such high-quality mRNA is lacking. Here, we present mRNAid, an open-source platform for therapeutic mRNA optimization, design and visualization that offers a variety of optimization strategies for sequence and structural features, allowing one to customize desired properties into their mRNA sequence. We experimentally demonstrate that transcripts optimized by mRNAid have characteristics comparable with commercially available sequences. To encompass additional aspects of mRNA design, we experimentally show that incorporation of certain uridine analogs and untranslated regions can further enhance stability, boost protein output and mitigate undesired immunogenicity effects. Finally, this study provides a roadmap for rational design of therapeutic mRNA transcripts.</p>","PeriodicalId":33994,"journal":{"name":"NAR Genomics and Bioinformatics","volume":"6 1","pages":"lqae028"},"PeriodicalIF":4.6,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10935487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140120982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
PyF2F: a robust and simplified fluorophore-to-fluorophore distance measurement tool for Protein interactions from Imaging Complexes after Translocation experiments. PyF2F:一种稳健、简化的荧光团对荧光团距离测量工具,用于从转位实验后的成像复合物中测量蛋白质相互作用。
IF 4.6
NAR Genomics and Bioinformatics Pub Date : 2024-03-12 eCollection Date: 2024-03-01 DOI: 10.1093/nargab/lqae027
Altair C Hernandez, Sebastian Ortiz, Laura I Betancur, Radovan Dojčilović, Andrea Picco, Marko Kaksonen, Baldo Oliva, Oriol Gallego
{"title":"PyF2F: a robust and simplified fluorophore-to-fluorophore distance measurement tool for Protein interactions from Imaging Complexes after Translocation experiments.","authors":"Altair C Hernandez, Sebastian Ortiz, Laura I Betancur, Radovan Dojčilović, Andrea Picco, Marko Kaksonen, Baldo Oliva, Oriol Gallego","doi":"10.1093/nargab/lqae027","DOIUrl":"10.1093/nargab/lqae027","url":null,"abstract":"<p><p>Structural knowledge of protein assemblies in their physiological environment is paramount to understand cellular functions at the molecular level. Protein interactions from Imaging Complexes after Translocation (PICT) is a live-cell imaging technique for the structural characterization of macromolecular assemblies in living cells. PICT relies on the measurement of the separation between labelled molecules using fluorescence microscopy and cell engineering. Unfortunately, the required computational tools to extract molecular distances involve a variety of sophisticated software programs that challenge reproducibility and limit their implementation to highly specialized researchers. Here we introduce PyF2F, a Python-based software that provides a workflow for measuring molecular distances from PICT data, with minimal user programming expertise. We used a published dataset to validate PyF2F's performance.</p>","PeriodicalId":33994,"journal":{"name":"NAR Genomics and Bioinformatics","volume":"6 1","pages":"lqae027"},"PeriodicalIF":4.6,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10939353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140132744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信