Impact Of The Energy Model On The Complexity Of RNA Folding With Pseudoknots

International audiencePredicting the folding of an RNA sequence, while allowing general pseudoknots (PK), consists in finding a minimal free-energy matching of its $n$ positions. Assuming independently contributing base-pairs, the problem can be solved in $\Theta(n^3)$-time using a variant of the maximal weighted matching. By contrast, the problem was previously proven NP-Hard in the more realistic nearest-neighbor energy model. In this work, we consider an intermediate model, called the stacking-pairs energy model. We extend a result by Lyngs\o, showing that RNA folding with PK is NP-Hard within a large class of parametrization for the model. We also show the approximability of the problem, by giving a practical $\Theta(n^3)$ algorithm that achieves at least a $5$-approximation for any parametrization of the stacking model. This contrasts nicely with the nearest-neighbor version of the problem, which we prove cannot be approximated within any positive ratio, unless $P=NP$.La prédiction du repliement, avec pseudonoeuds généraux, d'une séquence d'ARN de taille $n$ est équivalent à la recherche d'un couplage d'énergie libre minimale. Dans un modèle d'énergie simple, où chaque paire de base contribue indépendamment à l'énergie, ce problème peut être résolu en temps $\Theta(n^3)$ grâce à une variante d'un algorithme de couplage pondéré maximal. Cependant, le même problème a été démontré NP-difficile dans le modèle d'énergie dit des plus proches voisins. Dans ce travail, nous étudions les propriétés du problème sous un modèle d'empilements, constituant un modèle intermédiaire entre ceux d'appariement et des plus proches voisins. Nous démontrons tout d'abord que le repliement avec pseudo-noeuds de l'ARN reste NP-difficile dans de nombreuses valuations du modèle d'énergie. . Par ailleurs, nous montrons que ce problème est approximable, en proposant un algorithme polynomial garantissant une $1/5$-approximation. Ce résultat illustre une différence essentielle entre ce modèle et celui des plus proches voisins, pour lequel nous montrons qu'il ne peut être approché à aucun ratio positif par un algorithme en temps polynomial sauf si $N=NP$

RNA secondary structure prediction from multi-aligned sequences

It has been well accepted that the RNA secondary structures of most functional non-coding RNAs (ncRNAs) are closely related to their functions and are conserved during evolution. Hence, prediction of conserved secondary structures from evolutionarily related sequences is one important task in RNA bioinformatics; the methods are useful not only to further functional analyses of ncRNAs but also to improve the accuracy of secondary structure predictions and to find novel functional RNAs from the genome. In this review, I focus on common secondary structure prediction from a given aligned RNA sequence, in which one secondary structure whose length is equal to that of the input alignment is predicted. I systematically review and classify existing tools and algorithms for the problem, by utilizing the information employed in the tools and by adopting a unified viewpoint based on maximum expected gain (MEG) estimators. I believe that this classification will allow a deeper understanding of each tool and provide users with useful information for selecting tools for common secondary structure predictions.Comment: A preprint of an invited review manuscript that will be published in a chapter of the book `Methods in Molecular Biology'. Note that this version of the manuscript may differ from the published versio

Transnational strategy on the sustainable management and responsible use of non-native trees in the Alpine Space

Abstract Non-native tree species – defined as those species intentionally or unintentionally introduced by humans – have long been a part of the Alpine Space, providing numerous benefits, but also posing a potential threat to native biodiversity and related ecosystem services. Compared to the urban space where non-native trees comprise most tree species, the number of non-native trees in forests and plantations is relatively low. To evaluate potential risks and benefits of non-native trees in the Alpine Space, a transnational strategy for the responsible use and management of non-native trees is needed. The goals of the strategy are to tailor management practices for a sustainable and responsible use or admixture of non-native trees, to reduce the risks connected with the invasive potential of some non-native tree species, to help forests and urban areas to adapt to climate change, and to improve coordination and cooperation regarding best practices between different regions of the Alpine Space. A proposal was developed in a four-step process including expert-based assessment, stakeholder mapping, an extensive data review, and a public consultation. For implementing the strategy fully, strong collaboration among diverse stakeholders is anticipated and robust governance and an adequate long-term and fair funding scheme is needed

Automated analysis of digital fundus autofluorescence images of geographic atrophy in advanced age-related macular degeneration using confocal scanning laser ophthalmoscopy (cSLO)

BACKGROUND: Fundus autofluorescence (AF) imaging using confocal scanning laser ophthalmoscopy (cSLO) provides an accurate delineation of areas of geographic atrophy (GA). Automated computer-assisted methods for detecting and removing interfering vessels are needed to support the GA quantification process in longitudinal studies and in reading centres. METHODS: A test tool was implemented that uses region-growing techniques to segment GA areas. An algorithm for illuminating shadows can be used to process low-quality images. Agreement between observers and between three different methods was evaluated by two independent readers in a pilot study. Agreement and objectivity were assessed using the Bland-Altman approach. RESULTS: The new method (C) identifies vascular structures that interfere with the delineation of GA. Results are comparable to those of two commonly used procedures (A, B), with a mean difference between C and A of -0.67 mm(2 )(95% CI [-0.99, -0.36]), between B and A of -0.81 mm(2), (95% CI [-1.08, -0.53]), and between C and B of 0.15 mm(2 )(95% CI [-0.12, 0.41]). Objectivity of a method is quantified by the mean difference between observers: A 0.30 mm(2 )(95% CI [0.02, 0.57]), B -0.11 mm(2 )(95% CI [-0.28, 0.10]), and C 0.12 mm(2 )(95% CI [0.02, 0.22]). CONCLUSION: The novel procedure is comparable with regard to objectivity and inter-reader agreement to established methods of quantifying GA. It considerably speeds up the lengthy measurement process in AF with well defined GA zones

Role of 3′UTRs in the Translation of mRNAs Regulated by Oncogenic eIF4E—A Computational Inference

Eukaryotic cap-dependent mRNA translation is mediated by the initiation factor eIF4E, which binds mRNAs and stimulates efficient translation initiation. eIF4E is often overexpressed in human cancers. To elucidate the molecular signature of eIF4E target mRNAs, we analyzed sequence and structural properties of two independently derived polyribosome recruited mRNA datasets. These datasets originate from studies of mRNAs that are actively being translated in response to cells over-expressing eIF4E or cells with an activated oncogenic AKT: eIF4E signaling pathway, respectively. Comparison of eIF4E target mRNAs to mRNAs insensitive to eIF4E-regulation has revealed surprising features in mRNA secondary structure, length and microRNA-binding properties. Fold-changes (the relative change in recruitment of an mRNA to actively translating polyribosomal complexes in response to eIF4E overexpression or AKT upregulation) are positively correlated with mRNA G+C content and negatively correlated with total and 3′UTR length of the mRNAs. A machine learning approach for predicting the fold change was created. Interesting tendencies of secondary structure stability are found near the start codon and at the beginning of the 3′UTR region. Highly upregulated mRNAs show negative selection (site avoidance) for binding sites of several microRNAs. These results are consistent with the emerging model of regulation of mRNA translation through a dynamic balance between translation initiation at the 5′UTR and microRNA binding at the 3′UTR

Predicting RNA secondary structure by the comparative approach: how to select the homologous sequences

<p>Abstract</p> <p>Background</p> <p>The secondary structure of an RNA must be known before the relationship between its structure and function can be determined. One way to predict the secondary structure of an RNA is to identify covarying residues that maintain the pairings (Watson-Crick, Wobble and non-canonical pairings). This "comparative approach" consists of identifying mutations from homologous sequence alignments. The sequences must covary enough for compensatory mutations to be revealed, but comparison is difficult if they are too different. Thus the choice of homologous sequences is critical. While many possible combinations of homologous sequences may be used for prediction, only a few will give good structure predictions. This can be due to poor quality alignment in stems or to the variability of certain sequences. This problem of sequence selection is currently unsolved.</p> <p>Results</p> <p>This paper describes an algorithm, <it>SSCA</it>, which measures the suitability of sequences for the comparative approach. It is based on evolutionary models with structure constraints, particularly those on sequence variations and stem alignment. We propose three models, based on different constraints on sequence alignments. We show the results of the <it>SSCA </it>algorithm for predicting the secondary structure of several RNAs. <it>SSCA </it>enabled us to choose sets of homologous sequences that gave better predictions than arbitrarily chosen sets of homologous sequences.</p> <p>Conclusion</p> <p><it>SSCA </it>is an algorithm for selecting combinations of RNA homologous sequences suitable for secondary structure predictions with the comparative approach.</p

Transnational strategy on the sustainable management and responsible use of non-native trees in the Alpine Space

Non-native tree species – defined as those species intentionally or unintentionally introduced by humans – have longbeen a part of the Alpine Space, providing numerous benefits, but also posing a potential threat to native biodiversityand related ecosystem services. Compared to the urban space where non-native trees comprise most tree species,the number of non-native trees in forests and plantations is relatively low. To evaluate potential risks and benefits ofnon-native trees in the Alpine Space, a transnational strategy for the responsible use and management of non-nativetrees is needed. The goals of the strategy are to tailor management practices for a sustainable and responsible useor admixture of non-native trees, to reduce the risks connected with the invasive potential of some non-native treespecies, to help forests and urban areas to adapt to climate change, and to improve coordination and cooperationregarding best practices between different regions of the Alpine Space. A proposal was developed in a four-stepprocess including expert-based assessment, stakeholder mapping, an extensive data review, and a public consulta-tion. For implementing the strategy fully, strong collaboration among diverse stakeholders is anticipated and robustgovernance and an adequate long-term and fair funding scheme is needed

Global guidelines for the sustainable use of non-native trees to prevent tree invasions and mitigate their negative impacts

Sustainably managed non-native trees deliver economic and societal benefits with limited risk of spread to adjoining areas. However, some plantations have launched invasions that cause substantial damage to biodiversity and ecosystem services, while others pose substantial threats of causing such impacts. The challenge is to maximise the benefits of non-native trees, while minimising negative impacts and preserving future benefits and options. A workshop was held in 2019 to develop global guidelines for the sustainable use of non-native trees, using the Council of Europe – Bern Convention Code of Conduct on Invasive Alien Trees as a starting point. The global guidelines consist of eight recommendations: 1) Use native trees, or non-invasive non-native trees, in preference to invasive non-native trees; 2) Be aware of and comply with international, national, and regional regulations concerning non-native trees; 3) Be aware of the risk of invasion and consider global change trends; 4) Design and adopt tailored practices for plantation site selection and silvicultural management; 5) Promote and implement early detection and rapid response programmes; 6) Design and adopt tailored practices for invasive non-native tree control, habitat restoration, and for dealing with highly modified ecosystems; 7) Engage with stakeholders on the risks posed by invasive non-native trees, the impacts caused, and the options for management; and 8) Develop and support global networks, collaborative research, and information sharing on native and non-native trees. The global guidelines are a first step towards building global consensus on the precautions that should be taken when introducing and planting non-native trees. They are voluntary and are intended to complement statutory requirements under international and national legislation. The application of the global guidelines and the achievement of their goals will help to conserve forest biodiversity, ensure sustainable forestry, and contribute to the achievement of several Sustainable Development Goals of the United Nations linked with forest biodiversity

Incorporating background frequency improves entropy-based residue conservation measures

BACKGROUND: Several entropy-based methods have been developed for scoring sequence conservation in protein multiple sequence alignments. High scoring amino acid positions may correlate with structurally or functionally important residues. However, amino acid background frequencies are usually not taken into account in these entropy-based scoring schemes. RESULTS: We demonstrate that using a relative entropy measure that incorporates amino acid background frequency results in improved performance in identifying functional sites from protein multiple sequence alignments. CONCLUSION: Our results suggest that the application of appropriate background frequency information may lead to more biologically relevant results in many areas of bioinformatics