Recoding Strategies Research Articles

Multi-Phase Adaptive Recoding: An Analogue of Partial Retransmission in Batched Network Coding

Batched network coding (BNC) is a practical realization of random linear network coding (RLNC) designed for reliable network transmission in multi-hop networks with packet loss. By grouping coded packets into batches and restricting the use of RLNC within the same batch, BNC resolves the issue of RLNC that has high computational and storage costs at the intermediate nodes. A simple and common way to apply BNC is to fire and forget the recoded packets at the intermediate nodes, as BNC can act as an erasure code for data recovery. Due to the finiteness of batch size, the recoding strategy is a critical design that affects the throughput, the storage requirements, and the computational cost of BNC. The gain of the recoding strategy can be enhanced with the aid of a feedback mechanism, however the utilization and development of this mechanism is not yet standardized. In this paper, we investigate a multi-phase recoding mechanism for BNC. In each phase, recoding depends on the amount of innovative information remained at the current node after the transmission of the previous phases was completed. Relevant information can be obtained via hop-by-hop feedback; then, a more precise recoding scheme that allocates networking resources can be established. Unlike hop-by-hop retransmission schemes, the reception status of individual packets does not need to be known and packets to be sent in the next phase may not be the lost packets in the previous phase. Further, due to the loss-tolerance feature of BNC, it is unnecessary to pass all innovative information to the next node. This study illustrates that multi-phase recoding can significantly boost the throughput and reduce the decoding time as compared with the traditional single-phase recoding approach This opens a new window in developing better strategies for designing BNC rather than sending more batches in a blind manner.

Rare codon recoding for efficient noncanonical amino acid incorporation in mammalian cells.

The ability to genetically encode noncanonical amino acids (ncAAs) has empowered proteins with improved or previously unknown properties. However, existing strategies in mammalian cells rely on the introduction of a blank codon to incorporate ncAAs, which is inefficient and limits their widespread applications. In this study, we developed a rare codon recoding strategy that takes advantage of the relative rarity of the TCG codon to achieve highly selective and efficient ncAA incorporation through systematic engineering and big data-model predictions. We highlight the broad utility of this strategy for the incorporation of dozens of ncAAs into various functional proteins at the wild-type protein expression levels, as well as the synthesis of proteins with up to six-site ncAAs or four distinct ncAAs in mammalian cells for downstream applications.

Assessing recoding accounts of negative attentional templates using behavior and eye tracking.

Can we use attentional control to ignore known distractor features? Providing cues before a visual search trial about an upcoming distractor color (negative cue) can lead to reaction time benefits compared with no cue trials. This suggests top-down control may use negative templates to actively suppress distractor features, a notion that challenges the mechanisms of top-down control provided in many theories of attention. However, there is currently mixed support for this mechanism in the literature. Alternative explanations have been proposed, which do not require suppression within top-down control but instead involve recoding the negative cue into a positive template based on color or spatial layouts. In three experiments, we contrasted the predictions of active suppression and the recoding strategies. Across experiments, we found consistent evidence against a color recoding account. We also found evidence of accuracy, reaction time, and eye movement benefits when location recoding was not possible. These results suggest that prior benefits from negative cues cannot be explained exclusively by spatial or color recoding. The results indicate that active suppression likely plays a role in the attentional benefits following negative cues. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Shiftless, a Critical Piece of the Innate Immune Response to Viral Infection.

Since its initial characterization in 2016, the interferon stimulated gene Shiftless (SHFL) has proven to be a critical piece of the innate immune response to viral infection. SHFL expression stringently restricts the replication of multiple DNA, RNA, and retroviruses with an extraordinary diversity of mechanisms that differ from one virus to the next. These inhibitory strategies include the negative regulation of viral RNA stability, translation, and even the manipulation of RNA granule formation during viral infection. Even more surprisingly, SHFL is the first human protein found to directly inhibit the activity of the -1 programmed ribosomal frameshift, a translation recoding strategy utilized across nearly all domains of life and several human viruses. Recent literature has shown that SHFL expression also significantly impacts viral pathogenesis in mouse models, highlighting its in vivo efficacy. To help reconcile the many mechanisms by which SHFL restricts viral replication, we provide here a comprehensive review of this complex ISG, its influence over viral RNA fate, and the implications of its functions on the virus-host arms race for control of the cell.

Performance of Deaf Participants in an Abstract Visual Grammar Learning Task at Multiple Formal Levels: Evaluating the Auditory Scaffolding Hypothesis.

Previous research has hypothesized that human sequential processing may be dependent upon hearing experience (the “auditory scaffolding hypothesis”), predicting that sequential rule learning abilities should be hindered by congenital deafness. To test this hypothesis, we compared deaf signer and hearing individuals’ ability to acquire rules of different computational complexity in a visual artificial grammar learning task using sequential stimuli. As a group, deaf participants succeeded at all levels of the task; Bayesian analysis indicates that they successfully acquired each of several target grammars at ascending levels of the formal language hierarchy. Overall, these results do not support the auditory scaffolding hypothesis. However, age‐ and education‐matched hearing participants did outperform deaf participants in two out of three tested grammars. We suggest that this difference may be related to verbal recoding strategies in the two groups. Any verbal recoding strategies used by the deaf signers would be less effective because they would have to use the same visual channel required for the experimental task.

Compositional biases in RNA viruses: Causes, consequences and applications.

If each of the four nucleotides were represented equally in the genomes of viruses and the hosts they infect, each base would occur at a frequency of 25%. However, this is not observed in nature. Similarly, the order of nucleotides is not random (e.g., in the human genome, guanine follows cytosine at a frequency of ~0.0125, or a quarter the number of times predicted by random representation). Codon usage and codon order are also nonrandom. Furthermore, nucleotide and codon biases vary between species. Such biases have various drivers, including cellular proteins that recognize specific patterns in nucleic acids, that once triggered, induce mutations or invoke intrinsic or innate immune responses. In this review we examine the types of compositional biases identified in viral genomes and current understanding of the evolutionary mechanisms underpinning these trends. Finally, we consider the potential for large scale synonymous recoding strategies to engineer RNA virus vaccines, including those with pandemic potential, such as influenza A virus and Severe Acute Respiratory Syndrome Coronavirus Virus 2.This article is categorized under:RNA in Disease and Development > RNA in DiseaseRNA Evolution and Genomics > Computational Analyses of RNARNA Interactions with Proteins and Other Molecules > Protein‐RNA Recognition

Six-State Amino Acid Recoding is not an Effective Strategy to Offset Compositional Heterogeneity and Saturation in Phylogenetic Analyses.

Six-state amino acid recoding strategies are commonly applied to combat the effects of compositional heterogeneity and substitution saturation in phylogenetic analyses. While these methods have been endorsed from a theoretical perspective, their performance has never been extensively tested. Here, we test the effectiveness of six-state recoding approaches by comparing the performance of analyses on recoded and non-recoded data sets that have been simulated under gradients of compositional heterogeneity or saturation. In our simulation analyses, non-recoding approaches consistently outperform six-state recoding approaches. Our results suggest that six-state recoding strategies are not effective in the face of high saturation. Furthermore, while recoding strategies do buffer the effects of compositional heterogeneity, the loss of information that accompanies six-state recoding outweighs its benefits. In addition, we evaluate recoding schemes with 9, 12, 15, and 18 states and show that these consistently outperform six-state recoding. Our analyses of other recoding schemes suggest that under conditions of very high compositional heterogeneity, it may be advantageous to apply recoding using more than six states, but we caution that applying any recoding should include sufficient justification. Our results have important implications for the more than 90 published papers that have incorporated six-state recoding, many of which have significant bearing on relationships across the tree of life. [Compositional heterogeneity; Dayhoff 6-state recoding; S&R 6-state recoding; six-state amino acid recoding; substitution saturation.]

Genome recoding strategies to improve cellular properties: mechanisms and advances.

The genetic code, once believed to be universal and immutable, is now known to contain many variations and is not quite universal. The basis for genome recoding strategy is genetic code variation that can be harnessed to improve cellular properties. Thus, genome recoding is a promising strategy for the enhancement of genome flexibility, allowing for novel functions that are not commonly documented in the organism in its natural environment. Here, the basic concept of genetic code and associated mechanisms for the generation of genetic codon variants, including biased codon usage, codon reassignment, and ambiguous decoding, are extensively discussed. Knowledge of the concept of natural genetic code expansion is also detailed. The generation of recoded organisms and associated mechanisms with basic targeting components, including aminoacyl-tRNA synthetase–tRNA pairs, elongation factor EF-Tu and ribosomes, are highlighted for a comprehensive understanding of this concept. The research associated with the generation of diverse recoded organisms is also discussed. The success of genome recoding in diverse multicellular organisms offers a platform for expanding protein chemistry at the biochemical level with non-canonical amino acids, genetically isolating the synthetic organisms from the natural ones, and fighting viruses, including SARS-CoV2, through the creation of attenuated viruses. In conclusion, genome recoding can offer diverse applications for improving cellular properties in the genome-recoded organisms.

CpG-Recoding in Zika Virus Genome Causes Host-Age-Dependent Attenuation of Infection With Protection Against Lethal Heterologous Challenge in Mice.

Experimental increase of CpG dinucleotides in an RNA virus genome impairs infection providing a promising approach for vaccine development. While CpG recoding is an emerging and promising vaccine approach, little is known about infection phenotypes caused by recoded viruses in vivo. For example, infection phenotypes, immunogenicity, and protective efficacy induced by CpG-recoded viruses in different age groups were not studied yet. This is important, because attenuation of infection phenotypes caused by recoded viruses may depend on the population-based expression of cellular components targeting viral CpG dinucleotides. In the present study, we generated several Zika virus (ZIKV) variants with the increasing CpG content and compared infection in neonatal and adult mice. Increasing the CpG content caused host-age-dependent attenuation of infection with considerable attenuation in neonates and high attenuation in adults. Expression of the zinc-finger antiviral protein (ZAP)—the host protein targeting viral CpG dinucleotides—was also age-dependent. Similar to the wild-type virus, ZIKV variants with the increased CpG content evoked robust cellular and humoral immune responses and protection against lethal challenge. Collectively, the host age should be accounted for in future studies on mechanisms targeting viral CpG dinucleotides, development of safe dinucleotide recoding strategies, and applications of CpG-recoded vaccines.

TRNA functional signatures classify plastids as late-branching cyanobacteria

BackgroundEukaryotes acquired the trait of oxygenic photosynthesis through endosymbiosis of the cyanobacterial progenitor of plastid organelles. Despite recent advances in the phylogenomics of Cyanobacteria, the phylogenetic root of plastids remains controversial. Although a single origin of plastids by endosymbiosis is broadly supported, recent phylogenomic studies are contradictory on whether plastids branch early or late within Cyanobacteria. One underlying cause may be poor fit of evolutionary models to complex phylogenomic data.ResultsUsing Posterior Predictive Analysis, we show that recently applied evolutionary models poorly fit three phylogenomic datasets curated from cyanobacteria and plastid genomes because of heterogeneities in both substitution processes across sites and of compositions across lineages. To circumvent these sources of bias, we developed CYANO-MLP, a machine learning algorithm that consistently and accurately phylogenetically classifies (“phyloclassifies”) cyanobacterial genomes to their clade of origin based on bioinformatically predicted function-informative features in tRNA gene complements. Classification of cyanobacterial genomes with CYANO-MLP is accurate and robust to deletion of clades, unbalanced sampling, and compositional heterogeneity in input tRNA data. CYANO-MLP consistently classifies plastid genomes into a late-branching cyanobacterial sub-clade containing single-cell, starch-producing, nitrogen-fixing ecotypes, consistent with metabolic and gene transfer data.ConclusionsPhylogenomic data of cyanobacteria and plastids exhibit both site-process heterogeneities and compositional heterogeneities across lineages. These aspects of the data require careful modeling to avoid bias in phylogenomic estimation. Furthermore, we show that amino acid recoding strategies may be insufficient to mitigate bias from compositional heterogeneities. However, the combination of our novel tRNA-specific strategy with machine learning in CYANO-MLP appears robust to these sources of bias with high accuracy in phyloclassification of cyanobacterial genomes. CYANO-MLP consistently classifies plastids as late-branching Cyanobacteria, consistent with independent evidence from signature-based approaches and some previous phylogenetic studies.

Attenuation of Human Respiratory Viruses by Synonymous Genome Recoding.

Using computer algorithms and commercial DNA synthesis, one or more ORFs of a microbial pathogen such as a virus can be recoded and deoptimized by several strategies that may involve the introduction of up to thousands of nucleotide (nt) changes without affecting amino acid (aa) coding. The synonymous recoding strategies that have been applied to RNA viruses include: deoptimization of codon or codon-pair usage, which may reduce protein expression among other effects; increased content of immunomodulatory CpG and UpA RNA, which increase immune responses and thereby restrict viral replication; and substitution of serine and leucine codons with synonymous codons for which single-nt substitutions can yield nonsense codons, thus limiting evolutionary potential. This can reduce pathogen fitness and create potential live-attenuated vaccines that may have improved properties. The combined approach of genome recoding, synthetic biology, and reverse genetics offers several advantages for the generation of attenuated RNA viruses. First, synonymous recoding involves many mutations, which should reduce the rate and magnitude of de-attenuation. Second, increasing the amount of recoding can provide increased attenuation. Third, because there are no changes at the aa level, all of the relevant epitopes should be expressed. Fourth, attenuation frequently does not compromise immunogenicity, suggesting that the recoded viruses have increased immunogenicity per infectious particle. Synonymous deoptimization approaches have been applied to two important human viral pathogens, namely respiratory syncytial virus (RSV) and influenza A virus (IAV). This manuscript will briefly review the use of these different methods of synonymous recoding to generate attenuated RSV and IAV strains. It also will review the characterization of these vaccine candidates in vitro and in animal models, and describe several surprising findings with respect to phenotypic and genetic instability of some of these candidates.

Cracking the Code: The Impact of Orthographic Transparency and Morphological-Syllabic Complexity on Reading and Developmental Dyslexia.

Reading is an essential skill in modern societies, yet not all learners necessarily become proficient readers. Theoretical concepts (e.g., the orthographic depth hypothesis; the grain size theory) as well as empirical evidence suggest that certain orthographies are easier to learn than others. The present paper reviews the literature on orthographic transparency, morphological complexity, and syllabic complexity of alphabetic languages. These notions are elaborated to show that differences in reading acquisition reflect fundamental differences in the nature of the phonological recoding and reading strategies developing in response to the specific orthography to be learned. The present paper provides a narrative, cross-linguistic and integrated literature review, thereby contributing to the development of universal reading models and at the same time pointing out the important differences between orthographies at the more detailed level. Our review also yields suggestions to devise language-specific instruction and interventions for the development of the specific reading strategies required by the characteristics of the orthography being acquired.

IRES-dependent ribosome repositioning directs translation of a +1 overlapping ORF that enhances viral infection.

RNA structures can interact with the ribosome to alter translational reading frame maintenance and promote recoding that result in alternative protein products. Here, we show that the internal ribosome entry site (IRES) from the dicistrovirus Cricket paralysis virus drives translation of the 0-frame viral polyprotein and an overlapping +1 open reading frame, called ORFx, via a novel mechanism whereby a subset of ribosomes recruited to the IRES bypasses 37 nucleotides downstream to resume translation at the +1-frame 13th non-AUG codon. A mutant of CrPV containing a stop codon in the +1 frame ORFx sequence, yet synonymous in the 0-frame, is attenuated compared to wild-type virus in a Drosophila infection model, indicating the importance of +1 ORFx expression in promoting viral pathogenesis. This work demonstrates a novel programmed IRES-mediated recoding strategy to increase viral coding capacity and impact virus infection, highlighting the diversity of RNA-driven translation initiation mechanisms in eukaryotes.

Expanding the Nucleoside Recoding Toolkit: Revealing RNA Population Dynamics with 6-Thioguanosine.

RNA-sequencing (RNA-seq) measures RNA abundance in a biological sample but does not provide temporal information about the sequenced RNAs. Metabolic labeling can be used to distinguish newly made RNAs from pre-existing RNAs. Mutations induced from chemical recoding of the hydrogen bonding pattern of the metabolic label can reveal which RNAs are new in the context of a sequencing experiment. These nucleotide recoding strategies have been developed for a single uridine analogue, 4-thiouridine (s4U), limiting the scope of these experiments. Here we report the first use of nucleoside recoding with a guanosine analogue, 6-thioguanosine (s6G). Using TimeLapse sequencing (TimeLapse-seq), s6G can be recoded under RNA-friendly oxidative nucleophilic-aromatic substitution conditions to produce adenine analogues (substituted 2-aminoadenosines). We demonstrate the first use of s6G recoding experiments to reveal transcriptome-wide RNA population dynamics.

Recurrent emergence of structural variants of LTR retrotransposon CsRn1 evolving novel expression strategy and their selective expansion in a carcinogenic liver fluke, Clonorchis sinensis

Autonomous retrotransposons, in which replication and transcription are coupled, encode the essential gag and pol genes as a fusion or separate overlapping form(s) that are expressed in single transcripts regulated by a common upstream promoter. The element-specific expression strategies have driven development of relevant translational recoding mechanisms including ribosomal frameshifting to satisfy the protein stoichiometry critical for the assembly of infectious virus-like particles. Retrotransposons with different recoding strategies exhibit a mosaic distribution pattern across the diverse families of reverse transcribing elements, even though their respective distributions are substantially skewed towards certain family groups. However, only a few investigations to date have focused on the emergence of retrotransposons evolving novel expression strategy and causal genetic drivers of the structural variants. In this study, the bulk of genomic and transcribed sequences of a Ty3/gypsy-like CsRn1 retrotransposon in Clonorchis sinensis were analyzed for the comprehensive examination of its expression strategy. Our results demonstrated that structural variants with single open reading frame (ORF) have recurrently emerged from precedential CsRn1 copies encoding overlapping gag-pol ORFs by a single-nucleotide insertion in an upstream region of gag stop codon. In the parasite genome, some of the newly evolved variants appeared to undergo proliferative burst as active master lineages together with their ancestral copies. The genetic event was similarly observed in Opisthorchis viverrini, the closest neighbor of C. sinensis, whereas the resulting structural variants might have failed to overcome purifying selection and comprised minor remnant copies in the Opisthorchis genome.

Recoding strategies of German learners of English as a foreign language

This study investigated whether German learners of English as a foreign language (EFL) acquire additional recoding strategies that they do not need for recoding in the consistent German orthography. Based on the psycholinguistic grain size theory (Ziegler & Goswami, 2005) we expected students with little experience in EFL to use the same small-grain recoding strategy as in German, while more advanced students were expected to switch flexibly between small and large grain size recoding strategies when reading English nonwords. German students in Grades 5, 7, and 9, as well as university students were presented with an experimental nonword reading paradigm introduced by Goswami, Ziegler, Dalton, and Schneider (2003) which assesses the effects of language (nonwords derived from German vs. English), orthographic neighborhood, item length and presentation format (blocked vs. mixed) on reading latencies and accuracies. The data were analyzed using hierarchical linear models. The youngest age group did not use larger units to read English nonwords, but mostly applied simple grapheme-phoneme translation, as they would in their first language. University students were able to switch flexibly between large- and small size recoding strategies.

Arabic word processing and morphology induction through adaptive memory self-organisation strategies

Aim of the present study is to model the human mental lexicon, by focussing on storage and processing dynamics, as lexical organisation relies on the process of input recoding and adaptive strategies for long-term memory organisation. A fundamental issue in word processing is represented by the emergence of the morphological organisation level in the lexicon, based on paradigmatic relations between fully-stored word forms. Morphology induction can be defined as the task of perceiving and identifying morphological formatives within morphologically complex word forms, as a function of the dynamic interaction between lexical representations and distribution and degrees of regularity in lexical data.In the computational framework we propose here (TSOMs), based on Self-Organising Maps with Hebbian connections defined over a temporal layer, the identification/perception of surface morphological relations involves the alignment of recoded representations of morphologically-related input words. Facing a non-concatenative morphology such as the Arabic inflectional system prompts a reappraisal of morphology induction through adaptive organisation strategies, which affect both lexical representations and long-term storage.We will show how a strongly adaptive self-organisation during training is conducive to emergent relations between word forms, which are concurrently, redundantly and competitively stored in human mental lexicon, and to generalising knowledge of stored words to unknown forms.

Things Can Be Told Apart

A recent finding suggests that people use spatial distances of responses to separate nonspatial information in a simple categorization task like the Stroop task. It was suggested that the larger the distance becomes the easier the categorization will get; indeed, with large distances between response keys a smaller Stroop effect was observed by Lakens and colleagues (2011) as compared with small distances. This is a noteworthy finding albeit the published experiments suffer from two confounds which open the door for explanations of the distance effects in terms of spatial mismatch and recoding strategies. We conceptually replicated the results previously observed without these confounds and confirm the main result of Lakens et al. (2011) in that Stroop effects were significantly smaller if the distance between the response keys increased.

Modulation of stop codon read-through efficiency and its effect on the replication of murine leukemia virus.

ABSTRACTTranslational readthrough—suppression of termination at a stop codon—is exploited in the replication cycles of several viruses and represents a potential target for antiviral intervention. In the gammaretroviruses, typified by Moloney murine leukemia virus (MuLV), gag and pol are in the same reading frame, separated by a UAG stop codon, and termination codon readthrough is required for expression of the viral Gag-Pol fusion protein. Here, we investigated the effect on MuLV replication of modulating readthrough efficiency. We began by manipulating the readthrough signal in the context of an infectious viral clone to generate a series of MuLV variants in which readthrough was stimulated or reduced. In carefully controlled infectivity assays, it was found that reducing the MuLV readthrough efficiency only 4-fold led to a marked defect and that a 10-fold reduction essentially abolished replication. However, up to an ∼8.5-fold stimulation of readthrough (up to 60% readthrough) was well tolerated by the virus. These high levels of readthrough were achieved using a two-plasmid system, with Gag and Gag-Pol expressed from separate infectious clones. We also modulated readthrough by silencing expression of eukaryotic release factors 1 and 3 (eRF1 and eRF3) or by introducing aminoglycosides into the cells. The data obtained indicate that gammaretroviruses tolerate a substantial excess of viral Gag-Pol synthesis but are very sensitive to a reduction in levels of this polyprotein. Thus, as is also the case for ribosomal frameshifting, antiviral therapies targeting readthrough with inhibitory agents are likely to be the most beneficial.IMPORTANCE Many pathogenic RNA viruses and retroviruses use ribosomal frameshifting or stop codon readthrough to regulate expression of their replicase enzymes. These translational “recoding” processes are potential targets for antiviral intervention, but we have only a limited understanding of the consequences to virus replication of modulating the efficiency of recoding, particularly for those viruses employing readthrough. In this paper, we describe the first systematic analysis of the effect of increasing or decreasing readthrough efficiency on virus replication using the gammaretrovirus MuLV as a model system. We find unexpectedly that MuLV replication is only slightly inhibited by substantial increases in readthrough frequency, but as with other viruses that use recoding strategies, replication is quite sensitive to even modest reductions. These studies provide insights into both the readthrough process and MuLV replication and have implications for the selection of antivirals against gammaretroviruses.

Serine Codon-Usage Bias in Deep Phylogenomics: Pancrustacean Relationships as a Case Study

Phylogenomic analyses of ancient relationships are usually performed using amino acid data, but it is unclear whether amino acids or nucleotides should be preferred. With the 2-fold aim of addressing this problem and clarifying pancrustacean relationships, we explored the signals in the 62 protein-coding genes carefully assembled by Regier et al. in 2010. With reference to the pancrustaceans, this data set infers a highly supported nucleotide tree that is substantially different to the corresponding, but poorly supported, amino acid one. We show that the discrepancy between the nucleotide-based and the amino acids-based trees is caused by substitutions within synonymous codon families (especially those of serine-TCN and AGY). We show that different arthropod lineages are differentially biased in their usage of serine, arginine, and leucine synonymous codons, and that the serine bias is correlated with the topology derived from the nucleotides, but not the amino acids. We suggest that a parallel, partially compositionally driven, synonymous codon-usage bias affects the nucleotide topology. As substitutions between serine codon families can proceed through threonine or cysteine intermediates, amino acid data sets might also be affected by the serine codon-usage bias. We suggest that a Dayhoff recoding strategy would partially ameliorate the effects of such bias. Although amino acids provide an alternative hypothesis of pancrustacean relationships, neither the nucleotides nor the amino acids version of this data set seems to bring enough genuine phylogenetic information to robustly resolve the relationships within group, which should still be considered unresolved.