ViruClust: direct comparison of SARS-CoV-2 genomes and genetic variants in space and time.

MOTIVATION: The ongoing evolution of SARS-CoV-2 and the rapid emergence of variants of concern at distinct geographic locations have relevant implications for the implementation of strategies for controlling the COVID-19 pandemic. Combining the growing body of data and the evidence on potential functional implications of SARS-CoV-2 mutations can suggest highly effective methods for the prioritization of novel variants of potential concern, e.g. increasing in frequency locally and/or globally. However, these analyses may be complex, requiring the integration of different data and resources. We claim the need for a streamlined access to up-to-date and high-quality genome sequencing data from different geographic regions/countries, and the current lack of a robust and consistent framework for the evaluation/comparison of the results. RESULTS: To overcome these limitations, we developed ViruClust, a novel tool for the comparison of SARS-CoV-2 genomic sequences and lineages in space and time. ViruClust is made available through a powerful and intuitive web-based user interface. Sophisticated large-scale analyses can be executed with a few clicks, even by users without any computational background. To demonstrate potential applications of our method, we applied ViruClust to conduct a thorough study of the evolution of the most prevalent lineage of the Delta SARS-CoV-2 variant, and derived relevant observations. By allowing the seamless integration of different types of functional annotations and the direct comparison of viral genomes and genetic variants in space and time, ViruClust represents a highly valuable resource for monitoring the evolution of SARS-CoV-2, facilitating the identification of variants and/or mutations of potential concern. AVAILABILITY AND IMPLEMENTATION: ViruClust is openly available at http://gmql.eu/viruclust/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Sensitivity to Inflectional Morphemes in the Absence of Meaning: Evidence from a Novel Task.

A number of studies in different languages have shown that speakers may be sensitive to the presence of inflectional morphology in the absence of verb meaning (Caramazza et al. in Cognition 28(3):297-332, 1988; Clahsen in Behav Brain Sci 22(06):991-1013, 1999; Post et al. in Cognition 109(1):1-17, 2008). In this study, sensitivity to inflectional morphemes was tested in a purposely developed task with English-like nonwords. Native speakers of English were presented with pairs of nonwords and were asked to judge whether the two nonwords in each pair were the same or different. Each pair was composed either of the same nonword repeated twice, or of two slightly different nonwords. The nonwords were created taking advantage of a specific morphophonological property of English, which is that regular inflectional morphemes agree in voicing with the ending of the stem. Using stems ending in /l/, thus, we created: (1) nonwords ending in potential inflectional morphemes, vɔld, (2) nonwords without inflectional morphemes, vɔlt, and (3) a phonological control condition, vɔlb. Our new task endorses some strengths presented in previous work. As in Post et al. (2008) the task accounts for the importance of phonological cues to morphological processing. In addition, as in Caramazza et al. (1988) and contrary to Post et al. (2008), the task never presents bare-stems, making it unlikely that the participants would be aware of the manipulation performed. Our results are in line with Caramazza et al. (1988), Clahsen (1999) and Post et al. (2008), and offer further evidence that morphologically inflected nonwords take longer to be discriminated compared to uninflected nonwords.

The role of noninitial clusters in the Children's Test of Nonword Repetition: Evidence from children with language impairment and typically developing children.

The Children's Test of Nonword Repetition (CNRep) is one of the most popular tests of nonword repetition. The test is composed of nonwords of different length, and normative data suggest that children experience more difficulties in repeating long nonwords. An analysis of the distribution of phonological clusters in the test shows that noninitial clusters are unequally distributed in the test: They only appear in long nonwords (four and five syllables). For this reason, we hypothesized that the difficulties children encounter with long nonwords may be influenced by the phonological complexity of the clusters and not just by the challenge for working memory associated with length. To test the hypothesis, we compared repetition performance in long nonwords with and without a noninitial cluster in 18 children with language impairment and 18 typically developing children. The analysis shows that long nonwords with noninitial clusters are repeated less accurately by both groups. In addition, there was an interaction between cluster and age: The effect of cluster is absent in younger children and gradually increases with age. These findings suggest that phonological complexity may be having an impact on the length effect normally observed in the CNRep, and this impact may be particularly evident in older children.

Word position and stress effects in consonant cluster perception and production.

The aim of the present study was to investigate whether the saliency effect for word beginnings reported in children with dyslexia (Marshall & Van der Lely, 2009) can be found also in typically developing children. Thirty-four typically developing Italian children aged 8-10 years completed two specifically designed tasks: a production task and a perception task. Both tasks used nonwords containing clusters consisting of plosive plus liquid (e.g. pl). Clusters could be either in a stressed or in an unstressed syllable and could be either in initial position (first syllable) or in medial position (second syllable). In the production task, children were asked to repeat the nonwords. In the perception task, the children were asked to discriminate between two nonwords differing in one phoneme belonging to a cluster by reporting whether two repetitions were the same or different. Results from the production task showed that children are more accurate in repeating stressed than unstressed syllables, but there was no difference with respect to position of the cluster. Results from the perception task showed that children performed more accurately when discriminating word initial contrasts than when discriminating word medial contrasts, especially if the cluster was unstressed. Implications of this finding for clinical assessments are discussed.

EpiSurf: metadata-driven search server for analyzing amino acid changes within epitopes of SARS-CoV-2 and other viral species.

EpiSurf is a Web application for selecting viral populations of interest and then analyzing how their amino acid changes are distributed along epitopes. Viral sequences are searched within ViruSurf, which stores curated metadata and amino acid changes imported from the most widely used deposition sources for viral databases (GenBank, COVID-19 Genomics UK (COG-UK) and Global initiative on sharing all influenza data (GISAID)). Epitopes are searched within the open source Immune Epitope Database or directly proposed by users by indicating their start and stop positions in the context of a given viral protein. Amino acid changes of selected populations are joined with epitopes of interest; a result table summarizes, for each epitope, statistics about the overlapping amino acid changes and about the sequences carrying such alterations. The results may also be inspected by the VirusViz Web application; epitope regions are highlighted within the given viral protein, and changes can be comparatively inspected. For sequences mutated within the epitope, we also offer a complete view of the distribution of amino acid changes, optionally grouped by the location, collection date or lineage. Thanks to these functionalities, EpiSurf supports the user-friendly testing of epitope conservancy within selected populations of interest, which can be of utmost relevance for designing vaccines, drugs or serological assays. EpiSurf is available at two endpoints. Database URL: http://gmql.eu/episurf/ (for searching GenBank and COG-UK sequences) and http://gmql.eu/episurf_gisaid/ (for GISAID sequences).

Categorical and Dimensional Diagnoses of Dyslexia: Are They Compatible?

Dyslexia is often assessed using categorical diagnoses, and subtypes of dyslexia are also recognized in a categorical fashion. Children may meet the criteria for dyslexia, and they may more specifically meet the criteria for a subtype of it, and thus get a diagnosis. This approach to diagnosis clashes with the actual distribution of reading performance in children (which is normal and continuous), and it has received criticism. This article offers a conceptual framework for conciliating these two positions. In short, the proposal is to use a set of multicomponent continuous assessments of reading, rather than thresholds. The proposal is explained using original data obtained from a sample of 30 children (age 7 to 11), tested in the United Kingdom. Using an assessment based on categorical-thresholds, only five children in our sample qualify for extra assistance, and only one may get a diagnosis of dyslexia, while with the mixed system proposed, a few additional children in the gray area would receive attention. This approach would not discard previous categorical approaches such as those distinguishing between surface and phonological dyslexia, but it would rather see these subtypes of dyslexia as the instance of a lower score on the continuum obtained on a single component of the multicomponent assessment.

Reading as a Predictor of Complex Syntax. The Case of Relative Clauses.

BACKGROUND: The current study aims at better characterizing the role of reading skills as a predictor of comprehension of relative clauses. Well-established cross-linguistic evidence shows that children are more accurate in the comprehension of subject-extracted relative clauses in comparison to the object-extracted counterpart. Children with reading difficulties are known to perform less accurately on object relatives at the group level compared to typically developing children. Given that children's performance on reading tasks is shown to shape as a continuum, in the current study we attempted to use reading skills as a continuous variable to predict performance on relative clauses. METHODS: We examined the comprehension of relative clauses in a group of 30 English children (7-11 years) with varying levels of reading skills. Reading skills varied on a large spectrum, from poor readers to very skilled readers, as assessed by the YARC standardized test. The experimental task consisted of a picture-matching task. Children were presented with subject and object relative clauses and they were asked to choose one picture - out of four - that would best represent the sentence they heard. At the same time, we manipulated whether the subject and object nouns were either matching (both singular or both plural) or mismatching (one singular, the other plural) in number. RESULTS: Our analysis of accuracy shows that subject relatives were comprehended more accurately overall than object relatives, that responses to sentences with noun phrases mismatching in number were more accurate overall than the ones with matching noun phrases and that performance improved as a function of reading skills. Within the match subset, while the difference in accuracy between subject and object relatives is large in poor readers, the difference is reduced with better reading skills, almost disappearing in very skilled readers. DISCUSSION: Beside replicating the well-established findings on the subject-object asymmetry, number facilitation in the comprehension of relative clauses, and a better overall performance by skilled readers, these results indicate that strong reading skills may determine a reduction of the processing difficulty associated with the hardest object relative clause condition (i.e., match), causing a reduction of the subject-object asymmetry.