Näkökulmia kielellisten taitojen arviointiin ja kielellisen vaikeuden tunnistamiseen monikielisellä lapsella

Peer reviewe

Benchmarking methods for detecting differential states between conditions from multi-subject single-cell RNA-seq data

Single-cell RNA-sequencing (scRNA-seq) enables researchers to quantify transcriptomes of thousands of cells simultaneously and study transcriptomic changes between cells. scRNA-seq datasets increasingly include multisubject, multicondition experiments to investigate cell-type-specific differential states (DS) between conditions. This can be performed by first identifying the cell types in all the subjects and then by performing a DS analysis between the conditions within each cell type. Naive single-cell DS analysis methods that treat cells statistically independent are subject to false positives in the presence of variation between biological replicates, an issue known as the pseudoreplicate bias. While several methods have already been introduced to carry out the statistical testing in multisubject scRNA-seq analysis, comparisons that include all these methods are currently lacking. Here, we performed a comprehensive comparison of 18 methods for the identification of DS changes between conditions from multisubject scRNA-seq data. Our results suggest that the pseudobulk methods performed generally best. Both pseudobulks and mixed models that model the subjects as a random effect were superior compared with the naive single-cell methods that do not model the subjects in any way. While the naive models achieved higher sensitivity than the pseudobulk methods and the mixed models, they were subject to a high number of false positives. In addition, accounting for subjects through latent variable modeling did not improve the performance of the naive methods.</p

Short-Term Memory for Serial Order Moderates Aspects of Language Acquisition in Children With Developmental Language Disorder : Findings From the HelSLI Study

Previous studies of verbal short-term memory (STM) indicate that STM for serial order may be linked to language development and developmental language disorder (DLD). To clarify whether a domain-general mechanism is impaired in DLD, we studied the relations between age, non-verbal serial STM, and language competence (expressive language, receptive language, and language reasoning). We hypothesized that non-verbal serial STM differences between groups of children with DLD and typically developing (TD) children are linked to their language acquisition differences. Fifty-one children with DLD and sixty-six TD children participated as part of the HelSLI project in this cross-sectional study. The children were 4-6-year-old monolingual native Finnish speakers. They completed several tests of language and cognitive functioning, as well as new game-like tests of visual and auditory non-verbal serial STM. We used regression analyses to examine how serial STM moderates the effect of age on language. A non-verbal composite measure of serial visual and auditory STM moderated cross-sectional development of receptive language in the children with DLD. This moderation was not observed in the TD children. However, we found more rapid cross-sectional development of non-verbal serial STM in the TD children than in the children with DLD. The results suggest that children with DLD may be more likely to have compromised general serial STM processing and that superior non-verbal serial STM may be associated with better language acquisition in children with DLD.Peer reviewe

Quick reorganization of memory traces for morphologically complex words in young children

Formation of neural mechanisms for morphosyntactic processing in young children is still poorly understood. Here, we addressed neural processing and rapid online acquisition of familiar and unfamiliar combinations of morphemes. Three different types of morphologically complex words - derived, inflected, and novel (pseudostem + real suffix) - were presented in a passive listening setting to 16 typically developing 3-4-year old children (as part of a longitudinal Helsinki SLI follow-up study). The mismatch negativity (MMN) component of event-related potentials (ERP), an established index of long-term linguistic memory traces in the brain, was analysed separately for the initial and final periods of the exposure to these items. We found MMN response enhancement for the inflected words towards the end of the recording session, whereas no response change was observed for the derived or novel complex forms. This enhancement indicates rapid build-up of a new memory trace for the combination of real morphemes, suggesting a capacity for online formation of whole-form lexicalized representations as one of the morphological mechanisms in the developing brain. Furthermore, this enhancement increased with age, suggesting the development of automatic morphological processing circuits in the age range of 3-4 years.Peer reviewe

scShaper: an ensemble method for fast and accurate linear trajectory inference from single-cell RNA-seq data

MotivationComputational models are needed to infer a representation of the cells, i.e. a trajectory, from single-cell RNA-sequencing data that model cell differentiation during a dynamic process. Although many trajectory inference methods exist, their performance varies greatly depending on the dataset and hence there is a need to establish more accurate, better generalizable methods.ResultsWe introduce scShaper, a new trajectory inference method that enables accurate linear trajectory inference. The ensemble approach of scShaper generates a continuous smooth pseudotime based on a set of discrete pseudotimes. We demonstrate that scShaper is able to infer accurate trajectories for a variety of trigonometric trajectories, including many for which the commonly used principal curves method fails. A comprehensive benchmarking with state-of-the-art methods revealed that scShaper achieved superior accuracy of the cell ordering and, in particular, the differentially expressed genes. Moreover, scShaper is a fast method with few hyperparameters, making it a promising alternative to the principal curves method for linear pseudotemporal ordering.Availability and implementationscShaper is available as an R package at https://github.com/elolab/scshaper. The test data are available at https://doi.org/10.5281/zenodo.5734488.</p

ILoReg: a tool for high-resolution cell population identification from single-cell RNA-seq data

Single-cell RNA-seq allows researchers to identify cell populations based on unsupervised clustering of the transcriptome. However, subpopulations can have only subtle transcriptomic differences and the high dimensionality of the data makes their identification challenging.\nWe introduce ILoReg, an R package implementing a new cell population identification method that improves identification of cell populations with subtle differences through a probabilistic feature extraction step that is applied before clustering and visualization. The feature extraction is performed using a novel machine learning algorithm, called iterative clustering projection (ICP), that uses logistic regression and clustering similarity comparison to iteratively cluster data. Remarkably, ICP also manages to integrate feature selection with the clustering through L1-regularization, enabling the identification of genes that are differentially expressed between cell populations. By combining solutions of multiple ICP runs into a single consensus solution, ILoReg creates a representation that enables investigating cell populations with a high resolution. In particular, we show that the visualization of ILoReg allows segregation of immune and pancreatic cell populations in a more pronounced manner compared with current state-of-the-art methods.\nILoReg is available as an R package at https://bioconductor.org/packages/ILoReg.\nSupplementary data are available at Supplementary Information and Supplementary Files 1 and 2.\nMOTIVATION\nRESULTS\nAVAILABILITY\nSUPPLEMENTARY INFORMATIO

Cross-Sectional and Longitudinal Associations Between Quality of Parent–Child Interaction and Language Ability in Preschool-Age Children With Developmental Language Disorder

Publisher Copyright: © 2022 American Speech-Language-Hearing Association.Purpose: This study explores whether the quality of parent–child interaction is associated with language abilities cross-sectionally and longitudinally up to preschool-age among children with developmental language disorder (DLD). Method: Participants were 97 monolingual children with DLD and their parents from the Helsinki Longitudinal SLI study, HelSLI (baseline, age in years;months, M = 4;3, SD = 0;10), of which 71 pairs were followed longitudinally (age in years;months, M = 6;6, SD = 0;5). Video recordings from three play sessions were scored for child, parent, and dyadic behavior using Erickson’s sensitivity scale protocol and mutually responsive orientation at baseline. Children’s expressive and receptive language and language reasoning ability were assessed at baseline, and expressive and receptive language were assessed at follow-up. Results: At baseline, engaged child behavior, parent’s supportive guidance, and fluent and attuned dyadic behavior were associated with better receptive language ability, and engaged child behavior and dyadic synchrony were posi-tively associated with language reasoning ability in 3-to 6-year-olds. The child’s positive engagement and fluent and attuned dyadic behavior at baseline were associated with better expressive and receptive language abilities at follow-up in 6-to 7-year-olds, respectively. Conclusions: Fluent and attuned dyadic behavior is associated with better receptive language ability in preschool-age children. Parent behavior alone was not associated with language ability. A connected and mutually attuned parent– child relationship could be a protective factor for language development for children with DLD.Peer reviewe

Time-scale dynamics of proteome and transcriptome of the white-rot fungus Phlebia radiata : growth on spruce wood and decay effect on lignocellulose

Abstract Background The white-rot Agaricomycetes species Phlebia radiata is an efficient wood-decaying fungus degrading all wood components, including cellulose, hemicellulose, and lignin. We cultivated P. radiata in solid state cultures on spruce wood, and extended the experiment to 6 weeks to gain more knowledge on the time-scale dynamics of protein expression upon growth and wood decay. Total proteome and transcriptome of P. radiata were analyzed by peptide LC–MS/MS and RNA sequencing at specific time points to study the enzymatic machinery on the fungus’ natural growth substrate. Results According to proteomics analyses, several CAZy oxidoreductase class-II peroxidases with glyoxal and alcohol oxidases were the most abundant proteins produced on wood together with enzymes important for cellulose utilization, such as GH7 and GH6 cellobiohydrolases. Transcriptome additionally displayed expression of multiple AA9 lytic polysaccharide monooxygenases indicative of oxidative cleavage of wood carbohydrate polymers. Large differences were observed for individual protein quantities at specific time points, with a tendency of enhanced production of specific peroxidases on the first 2 weeks of growth on wood. Among the 10 class-II peroxidases, new MnP1-long, characterized MnP2-long and LiP3 were produced in high protein abundances, while LiP2 and LiP1 were upregulated at highest level as transcripts on wood together with the oxidases and one acetyl xylan esterase, implying their necessity as primary enzymes to function against coniferous wood lignin to gain carbohydrate accessibility and fungal growth. Majority of the CAZy encoding transcripts upregulated on spruce wood represented activities against plant cell wall and were identified in the proteome, comprising main activities of white-rot decay. Conclusions Our data indicate significant changes in carbohydrate-active enzyme expression during the six-week surveillance of P. radiata growing on wood. Response to wood substrate is seen already during the first weeks. The immediate oxidative enzyme action on lignin and wood cell walls is supported by detected lignin substructure sidechain cleavages, release of phenolic units, and visual changes in xylem cell wall ultrastructure. This study contributes to increasing knowledge on fungal genetics and lignocellulose bioconversion pathways, allowing us to head for systems biology, development of biofuel production, and industrial applications on plant biomass utilizing wood-decay fungi

Understanding developmental language disorder -The Helsinki longitudinal SLI study (HelSLI): A study protocol

BackgroundDevelopmental language disorder (DLD, also called specific language impairment, SLI) is a common developmental disorder comprising the largest disability group in pre-school-aged children. Approximately 7% of the population is expected to have developmental language difficulties. However, the specific etiological factors leading to DLD are not yet known and even the typical linguistic features appear to vary by language. We present here a project that investigates DLD at multiple levels of analysis and aims to make the reliable prediction and early identification of the difficulties possible. Following the multiple deficit model of developmental disorders, we investigate the DLD phenomenon at the etiological, neural, cognitive, behavioral, and psychosocial levels, in a longitudinal study of preschool children.MethodsIn January 2013, we launched the Helsinki Longitudinal SLI study (HelSLI) at the Helsinki University Hospital (http://tiny.cc/HelSLI). We will study 227 children aged 3–6 years with suspected DLD and their 160 typically developing peers. Five subprojects will determine how the child’s psychological characteristics and environment correlate with DLD and how the child’s well-being relates to DLD, the characteristics of DLD in monolingual versus bilingual children, nonlinguistic cognitive correlates of DLD, electrophysiological underpinnings of DLD, and the role of genetic risk factors. Methods include saliva samples, EEG, computerized cognitive tasks, neuropsychological and speech and language assessments, video-observations, and questionnaires.DiscussionThe project aims to increase our understanding of the multiple interactive risk and protective factors that affect the developing heterogeneous cognitive and behavioral profile of DLD, including factors affecting literacy development. This accumulated knowledge will form a heuristic basis for the development of new interventions targeting linguistic and non-linguistic aspects of DLD.<br /

How aware is the public of the existence, characteristics and causes of language impairment in childhood and where have they heard about it? A European survey

Public awareness of language impairment in childhood (Developmental Language Disorder (DLD)) has been identified as an important determiner of research and clinical service delivery, yet studies directly assessing public awareness are lacking. This study surveyed awareness across 18 countries of Europe.Method: A questionnaire developed by an international team asked whether respondents had heard of language impairment affecting children, what they thought its manifestations and causes were and where they had heard of it. Respondents were also asked whether they had heard of autism, dyslexia, ADD/ADHD and speech disorder. The questionnaire was administered to members of the public in 18 European countries. A total of 1519 responses were obtained, spanning 6 age groups, 4 educational level groups and 3 income level groups.Results: Across all but one country, significantly fewer people had heard of language impairment than any of the other disorders (or 60 % compared to over 90 % for autism). Awareness tended to be lowest in Eastern Europe and greatest in North-Western Europe, and was influenced by education level, age and income level. People in countries with overall low and overall high awareness differed in their views on manifestations and causes. People had heard of language impairment and autism the same way - most frequently through the media, including Internet, and less frequently through their child’s school or a medical professional.Discussion: The study confirms that awareness of language impairment and knowledge of the breadth of its manifestations are low. It also suggests opportunities for how to increase awareness, including greater media coverage of language impairment and more efficient use of venues such as schools and healthcare. Ways in which cultural and linguistic differences may influence public awareness efforts are discussed, including the translatability of clinical labels and scientific terms. These may impact the acceptance of a common term and definition across all countries. As awareness campaigns are gaining momentum, the findings of this study can serve as a baseline against which to compare future findings.peer-reviewe