-
Analytical Chemistry Oct 2023In this Perspective, we discuss the current status and advances in spatial transcriptomics technologies, which allow high-resolution mapping of gene expression in intact... (Review)
Review
In this Perspective, we discuss the current status and advances in spatial transcriptomics technologies, which allow high-resolution mapping of gene expression in intact cell and tissue samples. Spatial transcriptomics enables the creation of high-resolution maps of gene expression patterns within their native spatial context, adding an extra layer of information to the bulk sequencing data. Spatial transcriptomics has expanded significantly in recent years and is making a notable impact on a range of fields, including tissue architecture, developmental biology, cancer, and neurodegenerative and infectious diseases. The latest advancements in spatial transcriptomics have resulted in the development of highly multiplexed methods, transcriptomic-wide analysis, and single-cell resolution utilizing diverse technological approaches. In this Perspective, we provide a detailed analysis of the molecular foundations behind the main spatial transcriptomics technologies, including methods based on microdissection, sequencing, single-molecule FISH, spatial capturing, selection of regions of interest, and single-cell or nuclei dissociation. We contextualize the detection and capturing efficiency, strengths, limitations, tissue compatibility, and applications of these techniques as well as provide information on data analysis. In addition, this Perspective discusses future directions and potential applications of spatial transcriptomics, highlighting the importance of the continued development to promote widespread adoption of these techniques within the research community.
Topics: Transcriptome; Gene Expression Profiling; Tissue Array Analysis; Cell Nucleus; Data Analysis; Single-Cell Analysis
PubMed: 37814884
DOI: 10.1021/acs.analchem.3c02029 -
Child Development 2023The study of how children learn numbers has yielded one of the most productive research programs in cognitive development, spanning empirical and computational methods,...
The study of how children learn numbers has yielded one of the most productive research programs in cognitive development, spanning empirical and computational methods, as well as nativist and empiricist philosophies. This paper provides a tutorial on how to think computationally about learning models in a domain like number, where learners take finite data and go far beyond what they directly observe or perceive. To illustrate, this paper then outlines a model which acquires a counting procedure using observations of sets and words, extending the proposal of Piantadosi et al. (2012). This new version of the model responds to several critiques of the original work and outlines an approach which is likely appropriate for acquiring further aspects of mathematics.
Topics: Child; Humans; Learning; Cognition; Mathematics
PubMed: 37984061
DOI: 10.1111/cdev.14031 -
The British Journal of Developmental... Nov 2023Early mathematics skills relate to later mathematics achievement and educational attainment, which in turn predict career choice, income, health and financial...
Early mathematics skills relate to later mathematics achievement and educational attainment, which in turn predict career choice, income, health and financial decision-making. Critically, large differences exist among children in early mathematics performance, with parental mathematics engagement being a key predictor. However, most prior work has examined mothers' mathematics engagement with their preschool- and school-aged children. In this Registered Report, we tested concurrent associations between mothers' and fathers' engagement in mathematics activities with their 2- to 3-year-old toddlers and children's mathematics performance. Mothers and fathers did not differ in their engagement in mathematics activities, and both parents' mathematics engagement related to toddlers' mathematics skills. Fathers' mathematics engagement was associated with toddlers' number and mathematics language skills, but not their spatial skills. Mothers' mathematics engagement was only associated with toddlers' mathematics language skills. Critically, associations may be domain-specific, as parents' literacy engagement did not relate to measures of mathematics performance above their mathematics engagement. Mothers' and fathers' mathematics activities uniquely relate to toddlers' developing mathematics skills, and future work on the nuances of these associations is needed.
Topics: Female; Humans; Child, Preschool; Child; Parents; Mothers; Literacy; Educational Status; Mathematics
PubMed: 37431921
DOI: 10.1111/bjdp.12459 -
Nature Communications Sep 2023Single-molecule Real-time Isoform Sequencing (Iso-seq) of transcriptomes by PacBio can generate very long and accurate reads, thus providing an ideal platform for...
Single-molecule Real-time Isoform Sequencing (Iso-seq) of transcriptomes by PacBio can generate very long and accurate reads, thus providing an ideal platform for full-length transcriptome analysis. We present an integrated computational toolkit named TAGET for Iso-seq full-length transcript data analyses, including transcript alignment, annotation, gene fusion detection, and quantification analyses such as differential expression gene analysis and differential isoform usage analysis. We evaluate the performance of TAGET using a public Iso-seq dataset and newly sequenced Iso-seq datasets from tumor patients. TAGET gives significantly more precise novel splice site prediction and enables more accurate novel isoform and gene fusion discoveries, as validated by experimental validations and comparisons with RNA-seq data. We identify and experimentally validate a differential isoform usage gene ECM1, and further show that its isoform ECM1b may be a tumor-suppressor in laryngocarcinoma. Our results demonstrate that TAGET provides a valuable computational toolkit and can be applied to many full-length transcriptome studies.
Topics: Humans; Data Analysis; Gene Expression Profiling; Gene Fusion; RNA-Seq; Transcriptome; Extracellular Matrix Proteins
PubMed: 37741817
DOI: 10.1038/s41467-023-41649-0 -
PloS One 2023Testing whether data are from a normal distribution is a traditional problem and is of great concern for data analyses. The normality is the premise of many statistical...
Testing whether data are from a normal distribution is a traditional problem and is of great concern for data analyses. The normality is the premise of many statistical methods, such as t-test, Hotelling T2 test and ANOVA. There are numerous tests in the literature and the commonly used ones are Anderson-Darling test, Shapiro-Wilk test and Jarque-Bera test. Each test has its own advantageous points since they are developed for specific patterns and there is no method that consistently performs optimally in all situations. Since the data distribution of practical problems can be complex and diverse, we propose a Cauchy Combination Omnibus Test (CCOT) that is robust and valid in most data cases. We also give some theoretical results to analyze the good properties of CCOT. Two obvious advantages of CCOT are that not only does CCOT have a display expression for calculating statistical significance, but extensive simulation results show its robustness regardless of the shape of distribution the data comes from. Applications to South African Heart Disease and Neonatal Hearing Impairment data further illustrate its practicability.
Topics: Computer Simulation; Normal Distribution; Sample Size; Data Analysis
PubMed: 37535617
DOI: 10.1371/journal.pone.0289498 -
PLoS Computational Biology Aug 2023Dimensionality reduction is standard practice for filtering noise and identifying relevant features in large-scale data analyses. In biology, single-cell genomics...
Dimensionality reduction is standard practice for filtering noise and identifying relevant features in large-scale data analyses. In biology, single-cell genomics studies typically begin with reduction to 2 or 3 dimensions to produce "all-in-one" visuals of the data that are amenable to the human eye, and these are subsequently used for qualitative and quantitative exploratory analysis. However, there is little theoretical support for this practice, and we show that extreme dimension reduction, from hundreds or thousands of dimensions to 2, inevitably induces significant distortion of high-dimensional datasets. We therefore examine the practical implications of low-dimensional embedding of single-cell data and find that extensive distortions and inconsistent practices make such embeddings counter-productive for exploratory, biological analyses. In lieu of this, we discuss alternative approaches for conducting targeted embedding and feature exploration to enable hypothesis-driven biological discovery.
Topics: Humans; Data Analysis; Genomics
PubMed: 37590228
DOI: 10.1371/journal.pcbi.1011288 -
Neuropsychology Review Jun 2024Mathematics incorporates a broad range of skills, which includes basic early numeracy skills, such as subitizing and basic counting to more advanced secondary skills... (Meta-Analysis)
Meta-Analysis Review
Mathematics incorporates a broad range of skills, which includes basic early numeracy skills, such as subitizing and basic counting to more advanced secondary skills including mathematics calculation and reasoning. The aim of this review was to undertake a detailed investigation of the severity and pattern of early numeracy and secondary mathematics skills in people with epilepsy. Searches were guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Twenty adult studies and 67 child studies were included in this review. Overall, meta-analyses revealed significant moderate impairments across all mathematics outcomes in both adults (g= -0.676), and children (g= -0.593) with epilepsy. Deficits were also observed for specific mathematics outcomes. For adults, impairments were found for mathematics reasoning (g= -0.736). However, two studies found that mathematics calculation was not significantly impaired, and an insufficient number of studies examined early numeracy skills in adults. In children with epilepsy, significant impairments were observed for each mathematics outcome: early numeracy (g= -0.383), calculation (g= -0.762), and reasoning (g= -0.572). The gravity of impairments also differed according to the site of seizure focus for children and adults, suggesting that mathematics outcomes were differentially vulnerable to the location of seizure focus.
Topics: Humans; Epilepsy; Mathematics; Child; Adult
PubMed: 37490196
DOI: 10.1007/s11065-023-09600-8 -
Quarterly Journal of Experimental... Sep 2023Mathematics skills are associated with future employment, well-being, and quality of life. However, many adults and children fail to learn the mathematics skills they...
Mathematics skills are associated with future employment, well-being, and quality of life. However, many adults and children fail to learn the mathematics skills they require. To improve this situation, we need to have a better understanding of the processes of learning and performing mathematics. Over the past two decades, there has been a substantial growth in psychological research focusing on mathematics. However, to make further progress, we need to pay greater attention to the nature of, and multiple elements involved in, mathematical cognition. Mathematics is not a single construct; rather, overall mathematics achievement is comprised of proficiency with specific components of mathematics (e.g., number fact knowledge, algebraic thinking), which in turn recruit basic mathematical processes (e.g., magnitude comparison, pattern recognition). General cognitive skills and different learning experiences influence the development of each component of mathematics as well as the links between them. Here, I propose and provide evidence for a framework that structures how these components of mathematics fit together. This framework allows us to make sense of the proliferation of empirical findings concerning influences on mathematical cognition and can guide the questions we ask, identifying where we are missing both research evidence and models of specific mechanisms.
Topics: Child; Adult; Humans; Quality of Life; Cognition; Learning; Mathematics; Achievement
PubMed: 37129432
DOI: 10.1177/17470218231175325 -
Reports on Progress in Physics.... Aug 2023The last decade has witnessed a surge of theoretical and computational models to describe the dynamics of complex gene regulatory networks, and how these interactions... (Review)
Review
The last decade has witnessed a surge of theoretical and computational models to describe the dynamics of complex gene regulatory networks, and how these interactions can give rise to multistable and heterogeneous cell populations. As the use of theoretical modeling to describe genetic and biochemical circuits becomes more widespread, theoreticians with mathematical and physical backgrounds routinely apply concepts from statistical physics, non-linear dynamics, and network theory to biological systems. This review aims at providing a clear overview of the most important methodologies applied in the field while highlighting current and future challenges. It also includes hands-on tutorials to solve and simulate some of the archetypical biological system models used in the field. Furthermore, we provide concrete examples from the existing literature for theoreticians that wish to explore this fast-developing field. Whenever possible, we highlight the similarities and differences between biochemical and regulatory networks and 'classical' systems typically studied in non-equilibrium statistical and quantum mechanics.
Topics: Gene Regulatory Networks; Models, Biological; Nonlinear Dynamics
PubMed: 37531952
DOI: 10.1088/1361-6633/acec88 -
The Journal of Pediatrics Jan 2024To test whether preschool academic skills were associated with educational attainment in adolescence and whether associations differed between individuals born preterm...
OBJECTIVES
To test whether preschool academic skills were associated with educational attainment in adolescence and whether associations differed between individuals born preterm and at full term.
STUDY DESIGN
This prospective cohort study comprised 6924 individuals, including n = 444 (6.4%) adolescents born preterm (<37 weeks of gestation) from the Avon Longitudinal Study of Parents and Children. Preschool academic (mathematics and literacy) skills were rated by teachers at 4-5 years. Educational attainment at 16 years was informed by attaining a General Certificate of Secondary Education (GCSE) in key subjects mathematics and English. Logistic regressions assessed the association between preterm birth, preschool mathematics, and GCSE Mathematics and between preterm birth, preschool literacy, and GCSE English.
RESULTS
Similar numbers of adolescents born preterm and at term achieved a GCSE in mathematics and English (53.6 % vs 57.4% and 59.5% vs 63.9%, respectively; P values > .05). Higher preschool academic skill scores in mathematics were associated with greater odds of attaining GCSE Mathematics and preschool literacy skills were associated with GCSE English. Adolescents born preterm with higher preschool mathematics (OR: 1.51, CI: 1.14, 2.00) and literacy skills (OR: 1.57, CI: 1.10, 2.25) were more likely to attain GCSEs in the respective subject than their term-born counterparts with equal levels of preschool skills.
CONCLUSIONS
Preschool academic skills in mathematics and literacy are associated with educational attainment of preterm and term-born individuals in adolescence. Children born prematurely may benefit more from preschool mathematics and literacy skills for academic and educational success into adolescence than term-born individuals.
Topics: Child; Female; Humans; Infant, Newborn; Child, Preschool; Adolescent; Literacy; Longitudinal Studies; Premature Birth; Prospective Studies; Educational Status; Mathematics
PubMed: 37722555
DOI: 10.1016/j.jpeds.2023.113731