ABSTRACT
Clinical validity assessments of gene-disease associations underpin analysis and reporting in diagnostic genomics, and yet wide variability exists in practice, particularly in use of these assessments for virtual gene panel design and maintenance. Harmonization efforts are hampered by the lack of agreed terminology, agreed gene curation standards, and platforms that can be used to identify and resolve discrepancies at scale. We undertook a systematic comparison of the content of 80 virtual gene panels used in two healthcare systems by multiple diagnostic providers in the United Kingdom and Australia. The process was enabled by a shared curation platform, PanelApp, and resulted in the identification and review of 2,144 discordant gene ratings, demonstrating the utility of sharing structured gene-disease validity assessments and collaborative discordance resolution in establishing national and international consensus.
Subject(s)
Consensus , Data Curation/standards , Genetic Diseases, Inborn/genetics , Genomics/standards , Molecular Sequence Annotation/standards , Australia , Biomarkers/metabolism , Data Curation/methods , Delivery of Health Care , Gene Expression , Gene Ontology , Genetic Diseases, Inborn/diagnosis , Genetic Diseases, Inborn/pathology , Genomics/methods , Humans , Mobile Applications/supply & distribution , Terminology as Topic , United KingdomABSTRACT
PURPOSE: Several groups and resources provide information that pertains to the validity of gene-disease relationships used in genomic medicine and research; however, universal standards and terminologies to define the evidence base for the role of a gene in disease and a single harmonized resource were lacking. To tackle this issue, the Gene Curation Coalition (GenCC) was formed. METHODS: The GenCC drafted harmonized definitions for differing levels of gene-disease validity on the basis of existing resources, and performed a modified Delphi survey with 3 rounds to narrow the list of terms. The GenCC also developed a unified database to display curated gene-disease validity assertions from its members. RESULTS: On the basis of 241 survey responses from the genetics community, a consensus term set was chosen for grading gene-disease validity and database submissions. As of December 2021, the database contained 15,241 gene-disease assertions on 4569 unique genes from 12 submitters. When comparing submissions to the database from distinct sources, conflicts in assertions of gene-disease validity ranged from 5.3% to 13.4%. CONCLUSION: Terminology standardization, sharing of gene-disease validity classifications, and resolution of curation conflicts will facilitate collaborations across international curation efforts and in turn, improve consistency in genetic testing and variant interpretation.
Subject(s)
Databases, Genetic , Genomics , Genetic Testing , Genetic Variation , HumansABSTRACT
This study examines whether associations between enrollment in public and non-public PreK and children's (N = 508; Mage = 5.60 years in fall of kindergarten) math and language and literacy outcomes were more likely to be sustained through the spring of kindergarten for unconstrained versus constrained skills. Associations between public PreK and language, literacy, and math outcomes were more strongly sustained through the spring of kindergarten for unconstrained skills, relative to constrained skills. Only associations between non-public PreK and unconstrained language skills were sustained through the spring of kindergarten. Associations in the fall of kindergarten differed by family income and dual language learner (DLL) status but there was no subgroup variation by the spring of kindergarten. Implications for policy and practice are discussed.
Subject(s)
Language , Schools , Child , Child, Preschool , Educational Status , Humans , Literacy , MathematicsABSTRACT
ArrayExpress (https://www.ebi.ac.uk/arrayexpress) is an archive of functional genomics data from a variety of technologies assaying functional modalities of a genome, such as gene expression or promoter occupancy. The number of experiments based on sequencing technologies, in particular RNA-seq experiments, has been increasing over the last few years and submissions of sequencing data have overtaken microarray experiments in the last 12 months. Additionally, there is a significant increase in experiments investigating single cells, rather than bulk samples, known as single-cell RNA-seq. To accommodate these trends, we have substantially changed our submission tool Annotare which, along with raw and processed data, collects all metadata necessary to interpret these experiments. Selected datasets are re-processed and loaded into our sister resource, the value-added Expression Atlas (and its component Single Cell Expression Atlas), which not only enables users to interpret the data easily but also serves as a test for data quality. With an increasing number of studies that combine different assay modalities (multi-omics experiments), a new more general archival resource the BioStudies Database has been developed, which will eventually supersede ArrayExpress. Data submissions will continue unchanged; all existing ArrayExpress data will be incorporated into BioStudies and the existing accession numbers and application programming interfaces will be maintained.
Subject(s)
Oligonucleotide Array Sequence Analysis/methods , Single-Cell Analysis/methods , Software , Databases, Genetic , RNA-Seq/methodsABSTRACT
This cluster-randomized controlled study examined dual language learners (DLLs) in Norway who received a book-based language intervention program. About 464 DLLs aged 3-5 years in 123 early childhood classrooms participated in the study. The children were acquiring Norwegian as their second language in preschool and spoke a variety of first languages at home. They received a researcher-developed intervention that was organized around loosely scripted, content-rich shared reading in school and at home. Receiving the intervention had significant impacts on the children's second-language skills (effect sizes of d = .25-.66). In addition to supporting second-language vocabulary and grammar, the program with its focus on perspective taking during shared reading resulted in impacts on children's ability to shift perspectives and understand others' emotional states.
Subject(s)
Child Language , Language Development , Multilingualism , Reading , Adult , Books , Child, Preschool , Cluster Analysis , Educational Status , Emotions , Female , Humans , Linguistics , Male , Norway , Parent-Child Relations , Schools , VocabularyABSTRACT
BioStudies (www.ebi.ac.uk/biostudies) is a new public database that organizes data from biological studies. Typically, but not exclusively, a study is associated with a publication. BioStudies offers a simple way to describe the study structure, and provides flexible data deposition tools and data access interfaces. The actual data can be stored either in BioStudies or remotely, or both. BioStudies imports supplementary data from Europe PMC, and is a resource for authors and publishers for packaging data during the manuscript preparation process. It also can support data management needs of collaborative projects. The growth in multiomics experiments and other multi-faceted approaches to life sciences research mean that studies result in a diversity of data outputs in multiple locations. BioStudies presents a solution to ensuring that all these data and the associated publication(s) can be found coherently in the longer term.
Subject(s)
Biological Science Disciplines , Databases, Factual , Animals , Humans , Internet , SoftwareABSTRACT
This paper provides an overview of the features of caregiver input that facilitate language learning across early childhood. We discuss three dimensions of input quality: interactive, linguistic, and conceptual. All three types of input features have been shown to predict children's language learning, though perhaps through somewhat different mechanisms. We argue that input best designed to promote language learning is interactionally supportive, linguistically adapted, and conceptually challenging for the child's age/level. Furthermore, input features interact across dimensions to promote learning. Some but not all qualities of input vary based on parent socioeconomic status, language, or culture, and contexts such as book-reading or pretend play generate uniquely facilitative input features. The review confirms that we know a great deal about the role of input quality in promoting children's development, but that there is much more to learn. Future research should examine input features across the boundaries of the dimensions distinguished here.
Subject(s)
Language Development , Language , Parent-Child Relations , Parents , Books , Caregivers , Child, Preschool , Communication , Concept Formation , Culture , Humans , Infant , Knowledge , Learning , Linguistics , Reading , Social ClassABSTRACT
Expression Atlas (http://www.ebi.ac.uk/gxa) provides information about gene and protein expression in animal and plant samples of different cell types, organism parts, developmental stages, diseases and other conditions. It consists of selected microarray and RNA-sequencing studies from ArrayExpress, which have been manually curated, annotated with ontology terms, checked for high quality and processed using standardised analysis methods. Since the last update, Atlas has grown seven-fold (1572 studies as of August 2015), and incorporates baseline expression profiles of tissues from Human Protein Atlas, GTEx and FANTOM5, and of cancer cell lines from ENCODE, CCLE and Genentech projects. Plant studies constitute a quarter of Atlas data. For genes of interest, the user can view baseline expression in tissues, and differential expression for biologically meaningful pairwise comparisons-estimated using consistent methodology across all of Atlas. Our first proteomics study in human tissues is now displayed alongside transcriptomics data in the same tissues. Novel analyses and visualisations include: 'enrichment' in each differential comparison of GO terms, Reactome, Plant Reactome pathways and InterPro domains; hierarchical clustering (by baseline expression) of most variable genes and experimental conditions; and, for a given gene-condition, distribution of baseline expression across biological replicates.
Subject(s)
Databases, Genetic , Gene Expression Profiling , Plants/metabolism , Proteins/metabolism , Proteomics , Animals , Cell Line, Tumor , Humans , Plants/genetics , User-Computer InterfaceABSTRACT
The Consensus Coding Sequence (CCDS) project (http://www.ncbi.nlm.nih.gov/CCDS/) is a collaborative effort to maintain a dataset of protein-coding regions that are identically annotated on the human and mouse reference genome assemblies by the National Center for Biotechnology Information (NCBI) and Ensembl genome annotation pipelines. Identical annotations that pass quality assurance tests are tracked with a stable identifier (CCDS ID). Members of the collaboration, who are from NCBI, the Wellcome Trust Sanger Institute and the University of California Santa Cruz, provide coordinated and continuous review of the dataset to ensure high-quality CCDS representations. We describe here the current status and recent growth in the CCDS dataset, as well as recent changes to the CCDS web and FTP sites. These changes include more explicit reporting about the NCBI and Ensembl annotation releases being compared, new search and display options, the addition of biologically descriptive information and our approach to representing genes for which support evidence is incomplete. We also present a summary of recent and future curation targets.
Subject(s)
Databases, Genetic , Proteins/genetics , Animals , Exons , Genomics , Humans , Internet , Mice , Molecular Sequence Annotation , Sequence AnalysisABSTRACT
This mixed-method study examined the implementation and the challenges to implementation for participants in randomized controlled trials of two school-based programs for early adolescents: the Tier One Word Generation (WG) program, and the Tier Two Strategic Adolescent Reading Intervention (STARI). Levels of implementation for WG and STARI varied substantially across teachers and classrooms, with mean levels of 40% for fourth- and fifth-grade WG, 31% for sixth- and seventh-grade WG, and 47% for STARI. The three most common implementation challenges for WG were lack of time, multiple new programs/curricula happening at the same time, and time lost to testing and test prep. The three most common implementation challenges for STARI were student misbehavior, student absences, and time lost to testing and test prep. In order to succeed, efforts to find programs that work and to improve educational outcomes must address these formidable problems in U.S. public schools.
Subject(s)
Curriculum , Outcome and Process Assessment, Health Care , Reading , Schools , Adolescent , Child , HumansABSTRACT
Quality of teacher-child interactions is central to prekindergarten children's learning. In the United States, the quality of teacher-child interactions is commonly assessed using the teaching through interactions conceptual framework and an associ/ated observational tool, the Classroom Assessment Scoring System (CLASS). This study examined: (a) whether there was evidence supporting three distinctive domains of teacher-child interactions in Chile (construct validity) and (b) whether these domains predicted end-of-prekindergarten language, academic, and executive function skills in Chile (predictive validity). The sample consisted of 91 Chilean prekindergarten classrooms (1,868 four-year-old children). The findings support both construct and predictive validity of the teaching through interactions conceptual framework as assessed by the CLASS in Chile. Implications for cross-country comparison of quality of teacher-child interactions in prekindergarten classrooms are discussed.
Subject(s)
Child Development/physiology , Educational Measurement/standards , Faculty , Interpersonal Relations , Neuropsychological Tests/standards , Adult , Child, Preschool , Chile , Cross-Cultural Comparison , Female , Humans , Male , Middle Aged , Reproducibility of ResultsABSTRACT
OBJECTIVE: To identify differences and gaps in recommendations to patients for the management of sport-related concussion among FPs, emergency department physicians (EDPs), and pediatricians. DESIGN: A self-administered, multiple-choice survey was e-mailed to FPs, EDPs, and pediatricians. The survey had been assessed for content validity. SETTING: Two community teaching hospitals in the greater Toronto area in Ontario. PARTICIPANTS: Two hundred seventy physicians, including FPs, EDPs, and pediatricians, were invited to participate. MAIN OUTCOME MEASURES: Identification of sources of concussion management information, usefulness of concussion diagnosis strategies, and whether physicians use common terminology when explaining cognitive rest strategies to patients after sport-related concussions. RESULTS: The response rate was 43.7%. Surveys were completed by 70 FPs, 23 EDPs, and 11 pediatricians. In total, 49% of FP, 52% of EDP, and 27% of pediatrician respondents reported no knowledge of any consensus statements on concussion in sport, and 54% of FPs, 86% of EDPs, and 78% of pediatricians never used the Sport Concussion Assessment Tool, version 2. Only 49% of FPs, 57% of EDPs, and 36% of pediatricians always advised cognitive rest. CONCLUSION: This study identified large gaps in the knowledge of concussion guidelines and implementation of recommendations for treating patients with sport-related concussions. Although some physicians recommended physical and cognitive rest, a large proportion failed to consistently advise this strategy. Better knowledge transfer efforts should target all 3 groups of physicians.
Subject(s)
Athletic Injuries , Brain Concussion , Disease Management , Emergency Service, Hospital/standards , Family Practice/standards , Pediatrics/standards , Physicians/standards , Athletic Injuries/complications , Athletic Injuries/diagnosis , Athletic Injuries/therapy , Brain Concussion/diagnosis , Brain Concussion/etiology , Brain Concussion/therapy , Child , Health Care Surveys , Health Services Needs and Demand , Humans , Ontario , Practice Patterns, Physicians'/statistics & numerical data , Professional Practice/statistics & numerical data , Quality Assurance, Health CareABSTRACT
OBJECTIVE: To determine what proportion of patients experience an exacerbation of their symptoms as a result of premature return to play (RTP) and return to learn (RTL) following sport-related concussions. DESIGN: Retrospective study of electronic medical records from the office-based practice of one family and sport medicine physician who had systematically provided recommendations for cognitive and physical rest based on existing consensus recommendations. Two blinded authors independently reviewed each chart, which included Sport Concussion Assessment Tool (SCAT) and SCAT2 symptom self-report forms to determine whether an athlete had returned to play or learn prematurely. If there was a discrepancy between the 2 reviewers then a third author reviewed the charts. SETTING: A sport medicine and family practice in Ontario. The physician assessed sport-related concussions after self-referral or referral from other primary care physicians, teams, and schools. PARTICIPANTS: A total of 170 charts of 159 patients were assessed for sport-related concussion during a 5-year period (April 2006 to March 2011). All participants were students who were participating in sports at the time of injury. There were 41 concussions in elementary students, 95 concussions in high school students, and 34 concussions in college or university students. MAIN OUTCOME MEASURES: Premature RTP and RTL were defined as chart records documenting the recurrence or worsening of symptoms that accompanied the patients' RTP or RTL. Measures were compared using the earliest available SCAT forms and self-reporting. RESULTS: In 43.5% of concussion cases, the patient returned to sport too soon and in 44.7% of concussion cases, the patient returned to school too soon. Patients with a history of previous concussion required more days of rest before being permitted to participate in any physical activity than those patients without a previous history of concussion. Elementary school students required fewer days of rest before being permitted to return to any physical activity compared with high school students and college or university students. CONCLUSION: Currently, physicians recommend restrictions on mental and physical activity following sport-related concussion. This is done without clear guidelines as to what cognitive rest entails for students. Further research is required to determine how to implement a management plan for student athletes to facilitate complete recovery after concussion.
Subject(s)
Athletic Injuries/rehabilitation , Brain Concussion/rehabilitation , Family Practice , Students , Adolescent , Aptitude Tests , Athletes/classification , Athletes/psychology , Athletes/statistics & numerical data , Athletic Injuries/diagnosis , Athletic Injuries/physiopathology , Athletic Injuries/psychology , Brain Concussion/diagnosis , Brain Concussion/physiopathology , Brain Concussion/psychology , Canada , Child , Family Practice/methods , Family Practice/standards , Female , Health Planning Guidelines , Humans , Male , Outcome Assessment, Health Care , Physical Fitness/physiology , Physical Fitness/psychology , Retrospective Studies , Sports/classification , Sports/statistics & numerical data , Students/classification , Students/psychology , Students/statistics & numerical data , Young AdultABSTRACT
In the early years of the Journal of Child Language, there was considerable disagreement about the role of language input or adult-child interaction in children's language acquisition. The view that quantity and quality of input to language-learning children is relevant to their language development has now become widely accepted as a principle guiding advice to parents and the design of early childhood education programs, even if it is not yet uncontested in the field of language development. The focus on variation in the language input to children acquires particular educational relevance when we consider variation in access to academic language - features of language particularly valued in school and related to success in reading and writing. Just as many children benefit from language environments that are intentionally designed to ensure adequate quantity and quality of input, even more probably need explicit instruction in the features of language that characterize its use for academic purposes.
Subject(s)
Child Language , Child , Education , History, 20th Century , History, 21st Century , Humans , Language Development , Periodicals as Topic/history , Research/historyABSTRACT
The Hearts and Flowers (H&F) task is a computerized executive functioning (EF) assessment that has been used to measure EF from early childhood to adulthood. It provides data on accuracy and reaction time (RT) across three different task blocks (hearts, flowers, and mixed). However, there is a lack of consensus in the field on how to score the task that makes it difficult to interpret findings across studies. The current study, which includes a demographically diverse population of kindergarteners from Boston Public Schools (N = 946), compares the predictive and concurrent validity of 30 ways of scoring H&F, each with a different combination of accuracy, RT, and task block(s). Our exploratory results provide evidence supporting the use of a two-vector average score based on Zelazo et al.'s approach of adding accuracy and RT scores together only after individuals pass a certain accuracy threshold. Findings have implications for scoring future tablet-based developmental assessments.
ABSTRACT
BACKGROUND: The domestic pig is known as an excellent model for human immunology and the two species share many pathogens. Susceptibility to infectious disease is one of the major constraints on swine performance, yet the structure and function of genes comprising the pig immunome are not well-characterized. The completion of the pig genome provides the opportunity to annotate the pig immunome, and compare and contrast pig and human immune systems. RESULTS: The Immune Response Annotation Group (IRAG) used computational curation and manual annotation of the swine genome assembly 10.2 (Sscrofa10.2) to refine the currently available automated annotation of 1,369 immunity-related genes through sequence-based comparison to genes in other species. Within these genes, we annotated 3,472 transcripts. Annotation provided evidence for gene expansions in several immune response families, and identified artiodactyl-specific expansions in the cathelicidin and type 1 Interferon families. We found gene duplications for 18 genes, including 13 immune response genes and five non-immune response genes discovered in the annotation process. Manual annotation provided evidence for many new alternative splice variants and 8 gene duplications. Over 1,100 transcripts without porcine sequence evidence were detected using cross-species annotation. We used a functional approach to discover and accurately annotate porcine immune response genes. A co-expression clustering analysis of transcriptomic data from selected experimental infections or immune stimulations of blood, macrophages or lymph nodes identified a large cluster of genes that exhibited a correlated positive response upon infection across multiple pathogens or immune stimuli. Interestingly, this gene cluster (cluster 4) is enriched for known general human immune response genes, yet contains many un-annotated porcine genes. A phylogenetic analysis of the encoded proteins of cluster 4 genes showed that 15% exhibited an accelerated evolution as compared to 4.1% across the entire genome. CONCLUSIONS: This extensive annotation dramatically extends the genome-based knowledge of the molecular genetics and structure of a major portion of the porcine immunome. Our complementary functional approach using co-expression during immune response has provided new putative immune response annotation for over 500 porcine genes. Our phylogenetic analysis of this core immunome cluster confirms rapid evolutionary change in this set of genes, and that, as in other species, such genes are important components of the pig's adaptation to pathogen challenge over evolutionary time. These comprehensive and integrated analyses increase the value of the porcine genome sequence and provide important tools for global analyses and data-mining of the porcine immune response.
Subject(s)
Genomics , Immunity/genetics , Molecular Sequence Annotation , Swine/genetics , Swine/immunology , Animals , Cattle , Evolution, Molecular , Gene Duplication , Humans , Immunoglobulins/genetics , Mice , Models, Molecular , Protein Conformation , Receptors, Antigen, T-Cell/genetics , Receptors, KIR/genetics , Selection, Genetic , Species SpecificityABSTRACT
Previous reviews of the nature and consequences of adult-child book reading have focused on seeking impacts of interactive reading on the acquisition of vocabulary and emergent literacy skills. In this systematic review we examined to what extent there has been systematic study of the effects of interactive reading on four less frequently studied developmental outcomes important to children's academic and life prospects: socio-emotional and socio-cognitive (SEL) skills, narrative skills, grammar, and world knowledge. We identified 67 studies of interactive reading that met the inclusion criteria and that examined the targeted outcomes, using either experimental, quasi-experimental, correlational, or single-group intervention methods. We found that studies of effects on grammar and world knowledge outcomes were very sparsely represented; though narrative was often studied as an outcome, the wide variation in conceptualizing and assessing the construct hampered any clear conclusion about book-reading effects. The most robust research strand focused on SEL skill outcomes, though here too the outcome assessments varied widely. We speculate that better instrumented approaches to assessing vocabulary and emergent literacy have led to the persistent emphasis on these domains, despite robust evidence of only modest associations, and argue that work to develop sound shared measures of narrative and SEL skills would enable cross-study comparison and the accumulation of findings. In addition, we note that the various studies implicated different explanatory principles for the value of reading with children: specific interactional features (open-ended questions, following the child's lead, expanding child utterances) or content features (emotion-enhanced books, talk about mental states, science topics), raising another topic for more focused study in the future.
Subject(s)
Reading , Vocabulary , Adult , Humans , Child, Preschool , Literacy , Linguistics , BooksABSTRACT
The sustaining environments hypothesis theorizes that the lasting effects of PreK programs are contingent on the quality of the subsequent learning environment in early elementary school. The current study tests this theory by leveraging data from students (N = 462) who did and did not enroll in the Boston Public Schools (BPS) prekindergarten (PreK) program as well as features of their kindergarten instruction measured at the child- and classroom-levels using surveys and observations. Taken together, findings revealed limited evidence for the sustaining environments hypothesis. The bulk of the results were null, indicating that in general, associations between enrollment in BPS PreK and language, literacy, and math skills through the spring of kindergarten did not vary by kindergarten instructional experiences. When examining distinct types of instructional experiences, there were some inklings that child-level observational measures of kindergarten learning experiences-particularly those capturing constrained versus unconstrained instruction-were more predictive of PreK persistence than observed global classroom quality measures or survey-based measures of advanced instruction. However, these associations were not always specific to outcomes matching the content delivered during this instruction (math vs. literacy), consistent with the possibility of either cross-domain effects or that instructional variables are proxies for more general instructional practices. Findings for future research and theory are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
Subject(s)
Schools , Students , Educational Status , Humans , Learning , LiteracyABSTRACT
Measures of decoding and oral language have been shown to predict early reading comprehension across a wide variety of languages, though the timeframe and strength of the predictions vary by orthographic depth. This study is the first to examine predictors of early reading in Vietnamese, a transparent orthography of Romanized letters and diacritics. Eighty-two children in Hanoi, Vietnam, completed measures of decoding and oral language in kindergarten (phonological awareness, PA; rapid automatized naming, RAN; receptive and expressive vocabulary) and measures of decoding and reading comprehension in first grade. Average performance at the end of first grade, after just one year of formal instruction, was near ceiling on word reading but more variable on nonword and text reading. Kindergarten PA and RAN (but not vocabulary) predicted first-grade decoding after controlling for maternal education and kindergarten decoding, and PA was a stronger predictor than RAN (10% vs 4% of unique variance). The best predictors of first grade reading comprehension were first-grade decoding (47% of unique variance) and kindergarten expressive vocabulary (4% of unique variance) after controlling for maternal education. Overall, Vietnamese children became accurate and efficient decoders after one year of instruction. Findings from RAN and PA suggest their utility in guiding differentiated instruction on decoding. Kindergarten vocabulary, which differed as a function of maternal education, significantly predicted first-grade comprehension.
ABSTRACT
Parental engagement in home-based learning activities is linked to children's academic skills. Yet, interventions that try to enhance parental engagement-sometimes targeted to families with low levels of education-have small effects. This study aimed to inform supports for families by examining how different types of home-based learning activities influence academic skills during prekindergarten. We created four measures that assessed the frequency with which parents (N = 307) engaged in unconstrained and constrained language/literacy and math activities at home. Unconstrained language activities predicted gains in children's language skills, and unconstrained math activities were associated with gains in math skills. Both associations were larger for families with lower versus higher levels of parental education. Engagement in constrained activities did not predict gains in skills. Implications for practice and research are discussed. (PsycINFO Database Record (c) 2020 APA, all rights reserved).