ABSTRACT
Predicting protein-DNA binding specificity is a challenging yet essential task for understanding gene regulation. Protein-DNA complexes usually exhibit binding to a selected DNA target site, whereas a protein binds, with varying degrees of binding specificity, to a wide range of DNA sequences. This information is not directly accessible in a single structure. Here, to access this information, we present Deep Predictor of Binding Specificity (DeepPBS), a geometric deep-learning model designed to predict binding specificity from protein-DNA structure. DeepPBS can be applied to experimental or predicted structures. Interpretable protein heavy atom importance scores for interface residues can be extracted. When aggregated at the protein residue level, these scores are validated through mutagenesis experiments. Applied to designed proteins targeting specific DNA sequences, DeepPBS was demonstrated to predict experimentally measured binding specificity. DeepPBS offers a foundation for machine-aided studies that advance our understanding of molecular interactions and guide experimental designs and synthetic biology.
ABSTRACT
The Multidrug and toxic compound extrusion (MATE) and aluminium activated malate transporter (ALMT) gene families are involved in response to aluminium (Al) stress. In this study, we identified 48 MATE and 14 ALMT gene families in Vigna radiata genome and classified into 5 (MATE) and 3 (ALMT) clades by phylogenetic analysis. All the VrMATE and VrALMT genes were distributed across mungbean chromosomes. Tandem duplication was the main driving force for evolution and expansion of MATE gene family. Collinearity of mungbean with soybean indicated that MATE gene family is closely linked to Glycine max. Eight MATE transporters in clade 2 were found to be associated with previously characterized Al tolerance related MATEs in various plant species. Citrate exuding motif (CEM) was present in seven VrMATEs of clade 2. Promoter analysis revealed abundant plant hormone and stress responsive cis-elements. Results from quantitative real time-polymerase chain reaction (qRT-PCR) revealed that VrMATE19, VrMATE30 and VrALMT13 genes were markedly up-regulated at different time points under Al stress. Overall, this study offers a new direction for further molecular characterization of the MATE and ALMT genes in mungbean for Al tolerance.
Subject(s)
Aluminum , Phylogeny , Plant Proteins , Stress, Physiological , Vigna , Aluminum/toxicity , Vigna/genetics , Vigna/drug effects , Plant Proteins/genetics , Stress, Physiological/genetics , Gene Expression Regulation, Plant/drug effects , Gene Expression Profiling , Genome, Plant , Promoter Regions, GeneticABSTRACT
INTRODUCTION: Improving sustainable transportation options will help cities tackle growing challenges related to population health, congestion, climate change and inequity. Interventions supporting active transportation face many practical and political hurdles. Implementation science aims to understand how interventions or policies arise, how they can be translated to new contexts or scales and who benefits. Sustainable transportation interventions are complex, and existing implementation science frameworks may not be suitable. To apply and adapt implementation science for healthy cities, we have launched our mixed-methods research programme, CapaCITY/É. We aim to understand how, why and for whom sustainable transportation interventions are successful and when they are not. METHODS AND ANALYSIS: Across nine Canadian municipalities and the State of Victoria (Australia), our research will focus on two types of sustainable transportation interventions: all ages and abilities bicycle networks and motor vehicle speed management interventions. We will (1) document the implementation process and outcomes of both types of sustainable transportation interventions; (2) examine equity, health and mobility impacts of these interventions; (3) advance implementation science by developing a novel sustainable transportation implementation science framework and (4) develop tools for scaling up and scaling out sustainable transportation interventions. Training activities will develop interdisciplinary scholars and practitioners able to work at the nexus of academia and sustainable cities. ETHICS AND DISSEMINATION: This study received approval from the Simon Fraser University Office of Ethics Research (H22-03469). A Knowledge Mobilization Hub will coordinate dissemination of findings via a website; presentations to academic, community organisations and practitioner audiences; and through peer-reviewed articles.
Subject(s)
Capacity Building , Implementation Science , Humans , Cities , Canada , VictoriaABSTRACT
Analyzing and visualizing the tertiary structure and complex interactions of RNA is essential for being able to mechanistically decipher their molecular functions in vivo. Secondary structure visualization software can portray many aspects of RNA; however, these layouts are often unable to preserve topological correspondence since they do not consider tertiary interactions between different regions of an RNA molecule. Likewise, quaternary interactions between two or more interacting RNA molecules are not considered in secondary structure visualization tools. The RNAscape webserver produces visualizations that can preserve topological correspondence while remaining both visually intuitive and structurally insightful. RNAscape achieves this by designing a mathematical structural mapping algorithm which prioritizes the helical segments, reflecting their tertiary organization. Non-helical segments are mapped in a way that minimizes structural clutter. RNAscape runs a plotting script that is designed to generate publication-quality images. RNAscape natively supports non-standard nucleotides, multiple base-pairing annotation styles and requires no programming experience. RNAscape can also be used to analyze RNA/DNA hybrid structures and DNA topologies, including G-quadruplexes. Users can upload their own three-dimensional structures or enter a Protein Data Bank (PDB) ID of an existing structure. The RNAscape webserver allows users to customize visualizations through various settings as desired. URL: https://rnascape.usc.edu/.
Subject(s)
Algorithms , Nucleic Acid Conformation , RNA , Software , RNA/chemistry , Computer Graphics , Models, Molecular , InternetABSTRACT
The recognition and binding of nucleic acids (NAs) by proteins depends upon complementary chemical, electrostatic and geometric properties of the protein-NA binding interface. Structural models of protein-NA complexes provide insights into these properties but are scarce relative to models of unbound proteins. We present a deep learning approach for predicting protein-NA binding given the apo structure of a protein (PNAbind). Our method utilizes graph neural networks to encode spatial distributions of physicochemical and geometric properties of the protein molecular surface that are predictive of NA binding. Using global physicochemical encodings, our models predict the overall binding function of a protein and can discriminate between specificity for DNA or RNA binding. We show that such predictions made on protein structures modeled with AlphaFold2 can be used to gain mechanistic understanding of chemical and structural features that determine NA recognition. Using local encodings, our models predict the location of NA binding sites at the level of individual binding residues. Binding site predictions were validated against benchmark datasets, achieving AUROC scores in the range of 0.92-0.95. We applied our models to the HIV-1 restriction factor APOBEC3G and show that our predictions are consistent with experimental RNA binding data.
ABSTRACT
DNA recognition and targeting by transcription factors (TFs) through specific binding are fundamental in biological processes. Furthermore, the histidine protonation state at the TF-DNA binding interface can significantly influence the binding mechanism of TF-DNA complexes. Nevertheless, the role of histidine in TF-DNA complexes remains underexplored. Here, we employed all-atom molecular dynamics simulations using AlphaFold2-modeled complexes based on previously solved co-crystal structures to probe the role of the His-12 residue in the Extradenticle (Exd)-Sex combs reduced (Scr)-DNA complex when binding to Scr and Ultrabithorax (Ubx) target sites. Our results demonstrate that the protonation state of histidine notably affected the DNA minor-groove width profile and binding free energy. Examining flanking sequences of various binding affinities derived from SELEX-seq experiments, we analyzed the relationship between binding affinity and specificity. We uncovered how histidine protonation leads to increased binding affinity but can lower specificity. Our findings provide new mechanistic insights into the role of histidine in modulating TF-DNA binding.
Subject(s)
Drosophila Proteins , Homeodomain Proteins , Animals , Homeodomain Proteins/genetics , Histidine , Drosophila Proteins/metabolism , Drosophila melanogaster/metabolism , DNA/chemistry , Binding Sites , Transcription Factors/metabolismABSTRACT
We explored associations between neighbourhood environments and children and youths' moderate-to-vigorous physical activity (MVPA) during three different waves of the COVID-19 pandemic: spring 2020, fall 2020 and spring 2021, using three nationally representative cross-sectional surveys. In wave 2, higher dwelling density was associated with lower odds of a child achieving higher-level MVPA, however, the odds were higher in neighbourhoods with higher density that also had better access to parks. With regard to the social environment, ethnic concentration (wave 3) and greater deprivation (waves 1 and 3) were associated with lower odds of a child achieving higher-level MVPA. Results indicate that built and social environments were differently associated with MVPA levels depending on pandemic restrictions.
Subject(s)
COVID-19 , Pandemics , Humans , Child , Adolescent , Cross-Sectional Studies , Environment Design , COVID-19/epidemiology , Exercise , Social Environment , Residence CharacteristicsABSTRACT
This study explored the association between socioecological factors and outdoor physical activity (PA) and play in children with disabilities during the COVID-19 pandemic. Parents (N = 133) completed a survey to report changes in their child's outdoor PA and play during the pandemic (from prepandemic levels), and child, household, and neighborhood environment factors. Children with a PA-supporting parent and from multichild and White households had lower odds of reporting decreased outdoor PA. Children from multichild, higher income, married couple households and a PA-supporting parent had lower odds of decreased outdoor play. Living in neighborhoods with higher urbanization (i.e., high dwelling density, street intersections, and land-use mix) was associated with greater odds of decreased outdoor PA and play. Future research that uses larger and more representative samples of children with disabilities is needed to test for the multivariate effects of socioecological variables on outdoor PA and play.
Subject(s)
COVID-19 , Disabled Persons , Humans , Child , Adolescent , Exercise , Pandemics , Canada , ParentsABSTRACT
PURPOSE: The purposes of the current study were to identify risk profiles for nonadherence among children and youth (5-17 y) at the 6-month mark of the COVID-19 pandemic and to discuss similarities and differences between risk profiles identified in the current study and those identified at the 1-month mark of the pandemic. METHODS: Data were part of a nationally representative sample of 1143 parents (Mage = 43.07 y, SD = 8.16) of children and youth (5-17 y) living in Canada. Survey data were collected in October 2020. RESULTS: Results showed that 3.8% met all movement behavior recommendations, 16.2% met the physical activity recommendation, 27% met the screen time recommendation, and 63.8% met the sleep recommendation. Characteristics associated with nonadherence to all movement behaviors included low parental perceived capability to restrict screen time and decreased overall time spent outdoors. Characteristics associated with nonadherence to the physical activity and screen time recommendations included youth (12-17 y), low parental perceived capability to restrict screen time, decreased time spent outdoors, and increased screen time. CONCLUSION: Results emphasized the importance of parental perceived capability to restrict screen time and children's and youth's outdoor time and showed that pandemic-related factors have impacted children and youth differently.
Subject(s)
COVID-19 , Humans , Child , Adolescent , Pandemics , Sedentary Behavior , Exercise , Surveys and Questionnaires , SleepABSTRACT
Predicting specificity in protein-DNA interactions is a challenging yet essential task for understanding gene regulation. Here, we present Deep Predictor of Binding Specificity (DeepPBS), a geometric deep-learning model designed to predict binding specificity across protein families based on protein-DNA structures. The DeepPBS architecture allows investigation of different family-specific recognition patterns. DeepPBS can be applied to predicted structures, and can aid in the modeling of protein-DNA complexes. DeepPBS is interpretable and can be used to calculate protein heavy atom-level importance scores, demonstrated as a case-study on p53-DNA interface. When aggregated at the protein residue level, these scores conform well with alanine scanning mutagenesis experimental data. The inference time for DeepPBS is sufficiently fast for analyzing simulation trajectories, as demonstrated on a molecular-dynamics simulation of a Drosophila Hox-DNA tertiary complex with its cofactor. DeepPBS and its corresponding data resources offer a foundation for machine-aided protein-DNA interaction studies, guiding experimental choices and complex design, as well as advancing our understanding of molecular interactions.
ABSTRACT
High temperature challenges global crop production by limiting the growth and development of the reproductive structures and seed. It impairs the developmental stages of male and female gametogenesis, pollination, fertilization, endosperm formation and embryo development. Among these, the male reproductive processes are highly prone to abnormalities under high temperature at various stages of development. The disruption of source-sink balance is the main constraint for satisfactory growth of the reproductive structures which is disturbed at the level of sucrose import and utilization within the tissue. Seed development after fertilization is affected by modulation in the activity of enzymes involved in starch metabolism. In addition, the alteration in the seed-filling rate and its duration affects the seed weight and quality. The present review critically discusses the role of sugar metabolism in influencing the various stages of gamete and seed development under high temperature stress. It also highlights the interaction of the sugars with hormones that mediate the transport of sugars to sink tissues. The role of transcription factors for the regulation of sugar availability under high temperature has also been discussed. Further, the omics-based systematic investigation has been suggested to understand the synergistic or antagonistic interactions between sugars, hormones and reactive oxygen species at various points of sucrose flow from source to sink under high temperature stress.
Subject(s)
Plants , Seeds , Fertilization , Hormones/metabolism , Plants/metabolism , Seeds/metabolism , Sucrose/metabolism , Sugars/metabolism , TemperatureABSTRACT
An increase in technological interventions and ruthless urbanization in the name of development has deteriorated our environment over time and caused the buildup of heavy metals (HMs) in the soil and water resources. These heavy metals are gaining increased access into our food chain through the plant and/or animal-based products, to adversely impact human health. The issue of how to restrict the entry of HMs or modulate their response in event of their ingress into the plant system is worrisome. The current knowledge on the interactive-regulatory role and contribution of different physical, biophysical, biochemical, physiological, and molecular factors that determine the heavy metal availability-uptake-partitioning dynamics in the soil-plant-environment needs to be updated. The present review critically analyses the interactive overlaps between different adaptation and tolerance strategies that may be causally related to their cellular localization, conjugation and homeostasis, a relative affinity for the transporters, rhizosphere modifications, activation of efflux pumps and vacuolar sequestration that singly or collectively determine a plant's response to HM stress. Recently postulated role of gaseous pollutants such as SO2 and other secondary metabolites in heavy metal tolerance, which may be regulated at the whole plant and/or tissue/cell is discussed to delineate and work towards a "not so heavy" response of plants to heavy metals present in the contaminated soils.
Subject(s)
Metals, Heavy , Soil Pollutants , Biodegradation, Environmental , Humans , Metals, Heavy/analysis , Metals, Heavy/toxicity , Plants , Soil , Soil Pollutants/analysis , Soil Pollutants/toxicityABSTRACT
Daily life has changed for families due to the COVID-19 pandemic. The aim of this repeated cross-sectional study was to describe movement behaviours in Canadian children and youth 6 months into the pandemic (T2; October 2020) compared with the start of the pandemic (T1, April 2020). An online survey was distributed to parents (N = 1568) of children and/or youth (5-17 years; 58% girls) in October 2020. The survey assessed changes in movement behaviours (physical activity and play, sedentary behaviours, and sleep) from before the pandemic to October 2020 (T2). We compared these data with spring data (T1; April 2020; Moore et al. 2020; Int. J. Behav. Nutr. Phys. Act, 17:85) collected using identical methodology (N = 1472; 54% girls). We report correlations between movement behaviours and relevant parental factors and provide word frequency distributions for open-ended responses. During the second wave, 4.5% of children (4.6% girls; 4.3% boys) and 1.9% of youth (1.3% girls, 2.4% boys) met the movement guidelines (3.1% overall). Whereas, during the first wave, 4.8% (2.8% girls, 6.5% boys) of children and 0.6% (0.8% girls, 0.5% boys) of youth were meeting combined guidelines (2.6% overall). Parental support was correlated with their child's movement behaviours (T1 and T2). Our study demonstrates the ongoing challenges for children and youth to engage in healthy movement during the pandemic. Novelty: Our large-scale national study demonstrates that children and youth were not meeting the 24-hour movement guidelines during the second wave of the pandemic. Our findings illustrate the need to protect children and youth from the collateral consequences of the pandemic.
Subject(s)
COVID-19/epidemiology , COVID-19/prevention & control , Exercise/physiology , SARS-CoV-2 , Adolescent , Canada/epidemiology , Child , Child, Preschool , Cross-Sectional Studies , HumansABSTRACT
The current COVID-19 pandemic has disrupted daily behaviours of children and youth. Yet, little is known about how they are mentally coping with the pandemic-time changes to their lives. This study explores children and youths' self-reported subjective well-being (SWB) during the pandemic, and provides novel insights into the correlates of potential decrease, using data from a pan-Canadian online survey of 932 children/youth and their parents. SWB was measured based on perceived changes in 12 affective/emotional states. The results indicate that in spring 2020, at the height of the first wave of the pandemic, many children and youth were more bored (37.6%) and worried (31%) compared to pre-pandemic time. At the same time, many self-reported that they felt calmer (31.9%) and more rested (30%). A latent class analysis revealed that nearly half (49.4%) of surveyed children and youth reported patterns in changes in their emotional state that may contribute to lower SWB. Results from binomial logistic regression suggest that socio-demographic characteristics and size of the municipality were not associated with low pandemic-time SWB. Instead, other potentially modifiable factors such as having access to friends, indoor and outdoor spaces/places to play and exercise, and healthy movement behaviours during the pandemic, were correlated with a lower likelihood of reporting low SWB. The findings can inform pandemic-time public health policy relating to physical distancing, and in the longer term, mental and physical health promotion. The results will also help improve urban planning and design practices in creating healthier, more resilient and equitable communities.
ABSTRACT
Trans-acting expression quantitative trait loci (trans-eQTLs) account for ≥70% expression heritability and could therefore facilitate uncovering mechanisms underlying the origination of complex diseases. Identifying trans-eQTLs is challenging because of small effect sizes, tissue specificity, and a severe multiple-testing burden. Tejaas predicts trans-eQTLs by performing L2-regularized "reverse" multiple regression of each SNP on all genes, aggregating evidence from many small trans-effects while being unaffected by the strong expression correlations. Combined with a novel unsupervised k-nearest neighbor method to remove confounders, Tejaas predicts 18851 unique trans-eQTLs across 49 tissues from GTEx. They are enriched in open chromatin, enhancers, and other regulatory regions. Many overlap with disease-associated SNPs, pointing to tissue-specific transcriptional regulation mechanisms.
Subject(s)
Quantitative Trait Loci/genetics , Software , Chromatin/genetics , Computer Simulation , Genetic Predisposition to Disease , Genome-Wide Association Study , Genotype , Polymorphism, Single Nucleotide/genetics , Regression Analysis , Regulatory Sequences, Nucleic Acid/genetics , Risk FactorsABSTRACT
MOTIVATION: Methods to model dynamic changes in gene expression at a genome-wide level are not currently sufficient for large (temporally rich or single-cell) datasets. Variational autoencoders offer means to characterize large datasets and have been used effectively to characterize features of single-cell datasets. Here, we extend these methods for use with gene expression time series data. RESULTS: We present RVAgene: a recurrent variational autoencoder to model gene expression dynamics. RVAgene learns to accurately and efficiently reconstruct temporal gene profiles. It also learns a low dimensional representation of the data via a recurrent encoder network that can be used for biological feature discovery, and from which we can generate new gene expression data by sampling the latent space. We test RVAgene on simulated and real biological datasets, including embryonic stem cell differentiation and kidney injury response dynamics. In all cases, RVAgene accurately reconstructed complex gene expression temporal profiles. Via cross validation, we show that a low-error latent space representation can be learnt using only a fraction of the data. Through clustering and gene ontology term enrichment analysis on the latent space, we demonstrate the potential of RVAgene for unsupervised discovery. In particular, RVAgene identifies new programs of shared gene regulation of Lox family genes in response to kidney injury. AVAILABILITY AND IMPLEMENTATION: All datasets analyzed in this manuscript are publicly available and have been published previously. RVAgene is available in Python, at GitHub: https://github.com/maclean-lab/RVAgene; Zenodo archive: http://doi.org/10.5281/zenodo.4271097. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
ABSTRACT
This paper explores patterns of increased/ decreased physical activity, sedentary and sleep behaviours among Canadian children and youth aged 5-17 years during the COVID-19 pandemic, and examines how these changes are associated with the built environment near residential locations. A cluster analysis identified two groups who were primarily distinguished by the changes in outdoor activities. Compliance to 24-hour movement guidelines was low among both groups. For children, houses (versus apartments) was correlated with increased outdoor activities; proximity to major roads was a barrier. For youth, low dwelling density, and access to parks in high-density neighbourhoods, increased the odds of increased outdoor activities during the pandemic. Our findings can inform future urban and health crisis planning practices by providing new insights into the desirable public health messaging and characteristics of healthy and resilient communities.
Subject(s)
Built Environment/statistics & numerical data , Coronavirus Infections , Health Behavior , Pandemics , Pneumonia, Viral , Adolescent , Betacoronavirus/isolation & purification , COVID-19 , Canada , Child , Child, Preschool , Exercise/physiology , Female , Humans , Male , Residence Characteristics , SARS-CoV-2ABSTRACT
BACKGROUND: Healthy childhood development is fostered through sufficient physical activity (PA; including time outdoors), limiting sedentary behaviours (SB), and adequate sleep; collectively known as movement behaviours. Though the COVID-19 virus outbreak has changed the daily lives of children and youth, it is unknown to what extent related restrictions may compromise the ability to play and meet movement behaviour recommendations. This secondary data analysis examined the immediate impacts of COVID-19 restrictions on movement and play behaviours in children and youth. METHODS: A national sample of Canadian parents (n = 1472) of children (5-11 years) or youth (12-17 years) (54% girls) completed an online survey that assessed immediate changes in child movement and play behaviours during the COVID-19 outbreak. Behaviours included PA and play, SB, and sleep. Family demographics and parental factors that may influence movement behaviours were assessed. Correlations between behaviours and demographic and parental factors were determined. For open-ended questions, word frequency distributions were reported. RESULTS: Only 4.8% (2.8% girls, 6.5% boys) of children and 0.6% (0.8% girls, 0.5% boys) of youth were meeting combined movement behaviour guidelines during COVID-19 restrictions. Children and youth had lower PA levels, less outside time, higher SB (including leisure screen time), and more sleep during the outbreak. Parental encouragement and support, parental engagement in PA, and family dog ownership were positively associated with healthy movement behaviours. Although families spent less time in PA and more time in SB, several parents reported adopting new hobbies or accessing new resources. CONCLUSIONS: This study provides evidence of immediate collateral consequences of the COVID-19 outbreak, demonstrating an adverse impact on the movement and play behaviours of Canadian children and youth. These findings can guide efforts to preserve and promote child health during the COVID-19 outbreak and crisis recovery period, and to inform strategies to mitigate potential harm during future pandemics.
Subject(s)
Coronavirus Infections/epidemiology , Exercise , Play and Playthings , Pneumonia, Viral/epidemiology , Sedentary Behavior , Sleep , Adolescent , Betacoronavirus , COVID-19 , Canada/epidemiology , Child , Child, Preschool , Cross-Sectional Studies , Family Characteristics , Female , Health Behavior , Health Status , Humans , Male , Pandemics , Parents , SARS-CoV-2 , Surveys and QuestionnairesABSTRACT
The neighbourhood environment may enable active aging by allowing the integration of walking into an older adult's daily routine. This study explores the relationship between the neighbourhood built environment and walking among a small group of older adults in a large suburban municipality in Canada. In-depth interviews using a photo-voice approach revealed that the participants walked largely to accumulated physical activity. Older adults who lived in either conventional residential or condominium neighbourhoods discussed poor traffic conditions and lack of benches/trees/places as barriers, and proximity to parks and access to shops as enablers to walking. Poor sidewalk quality, absence of street lights and personal safety concerns were major barriers to walking only for those living in suburban residential neighbourhoods. Our results indicate that high quality- and safe walking infrastructure may facilitate walking for physical activity among older adults living in the suburban communities.
Subject(s)
City Planning , Environment Design/statistics & numerical data , Health Behavior , Suburban Population/statistics & numerical data , Walking/statistics & numerical data , Aged , Canada , Female , Humans , Male , Residence Characteristics , Surveys and QuestionnairesABSTRACT
BACKGROUND: Children's independent mobility (CIM) is critical to healthy development in childhood. The physical layout and social characteristics of neighbourhoods can impact opportunities for CIM. While global evidence is mounting on CIM, to the authors' knowledge, Canadian data on CIM and related health outcomes (i.e., physical activity (PA) behaviour) are missing. The purpose of this study was to examine if CIM is related to multiple characteristics of accelerometry-measured PA behaviour (total PA, light PA, moderate-to-vigorous PA, time spent sedentary) and whether associations between CIM and PA behaviour systematically vary by place of residence, stratifying by gender and type of day/period (weekdays, after-school, weekend). METHODS: Participants were recruited through Project BEAT (Built Environment and Active Transport; http://www.beat.utoronto.ca). Children (n = 856) were stratified into four neighbourhood classifications based on the period of neighbourhood development (urban built environment (BE) (old BE) versus inner-suburban BE (new BE)) and socioeconomic status (SES; low SES and high SES). Physical activity was measured via accelerometry (ActiGraph GT1M). CIM was assessed via parental report and two categories were created (low CIM, n = 332; high CIM, n = 524). A series of two-factor ANOVAs were used to determine gender-specific differences in PA for weekdays, weekend days and the after-school period, according to level of CIM, across four neighbourhood classifications. RESULTS: Children who were granted at least some independent mobility (high CIM) had more positive PA profiles across the school week, during the after-school period, and over the weekend; they were also less sedentary. The influence of CIM on PA behaviour was particularly salient during the after-school period. Associations of CIM with PA varied by gender, and also by neighbourhood classification. CIM seemed to matter more in urban neighbourhoods for boys and suburban neighbourhoods for girls. CONCLUSION: Our findings highlight the importance of independent mobility to multiple characteristics of children's PA behaviour across the week. Furthermore, they emphasize that independent mobility-activity relationships need to be considered by gender and the type of neighbourhood independent mobility is offered in. Future work will focus on developing a predictive model of CIM that could be used to inform decision-making around alleviating barriers to CIM.