Biology subjects

Paul, R.

Publications and source records attributed to Paul, R..

5 recordsLinked to original sources

bioRxiv2018

Group Based Trajectory Analysis of Cognitive Outcomes in Children with Perinatal HIV

BackgroundCognitive impairment is common in children with perinatally-acquired HIV (pHIV). It is not known whether exposure to HIV-related neuropathogenic mechanisms during vulnerable periods of neurodevelopment may produce distinct long-term cognitive phenotypes as children age. We used group based trajectory modeling to identify clusters of children with pHIV following a unique developmental trajectory across age and predictors of belonging to select cognitive trajectory groups.\n\nMethodsParticipants included children aged 1 to 17 enrolled in the PREDICT resilience study, a cohort study of children with pHIV in Thailand and Cambodia. Cognitive testing was conducted semi-annually over three years. Group based trajectory analyses determined subgroups of children with differing cognitive trajectories using maximum likelihood estimates and Bayesian statistics. Multiple logistic regression identified baseline factors associated with belonging to the lowest scoring trajectory group.\n\nResultsThree distinct cognitive phenotypes were identified for each neurocognitive test categorized as high, medium and low scoring groups. A subgroup of children demonstrated normal developmental patterns for Color Trails Test 1 and 2. Children in the low trajectory group were more likely to present at an older age (>8 years, OR: 2.72; p 0.01) and report lower household income level (OR: 0.33-0.42; p<0.005). Neither CD4 nadir nor treatment arm was associated with cognitive trajectory status.\n\nConclusionOur study reflects the benefit of using group based trajectory modeling to classify the heterogeneity in cognitive outcomes of children with pHIV. Children were described as belonging to three distinct subgroups determined at study onset alluding to the fact that cognitive outcomes are likely to be determined at an early age with little variability over time in children with pHIV. Demographic variables, including older age at presentation and household income, were associated with low scoring cognitive trajectories, whereas HIV related variables were not. These findings mirror other studies and demonstrate the impact of socioeconomic factors on cognitive development in children with pHIV.

neuroscience↗

bioRxiv2018

Generation of a versatile BiFC ORFeome library for analyzing protein-protein interactions in live Drosophila

Transcription factors achieve specificity by establishing intricate interaction networks that will change depending on the cell context. Capturing these interactions in live condition is however a challenging issue that requires sensitive and non-invasive methods. We present a set of fly lines, called \"multicolor BiFC library\", which covers most of the Drosophila transcription factors for performing Bimolecular Fluorescence Complementation (BiFC). The multicolor BiFC library can be used to probe binary or tripartite interactions and is compatible for large-scale interaction screens. The library can also be coupled with established Drosophila genetic resources to analyze interactions in the developmentally relevant expression domain of each protein partner. We provide proof of principle experiments of these various applications, using Hox proteins in the live Drosophila embryo as a case study. Overall this novel collection of ready-to-use fly lines constitutes an unprecedented genetic toolbox for the identification and analysis of protein-protein interactions in vivo.

genomics↗

bioRxiv2018

EnTAP: Bringing Faster and Smarter Functional Annotation to Non-Model Eukaryotic Transcriptomes

EnTAP (Eukaryotic Non-Model Transcriptome Annotation Pipeline) was designed to improve the accuracy, speed, and flexibility of functional gene annotation for de novo assembled transcriptomes in non-model eukaryotes. This software package addresses the fragmentation and related assembly issues that result in inflated transcript estimates and poor annotation rates, while focusing primarily on protein-coding transcripts. Following filters applied through assessment of true expression and frame selection, open-source tools are leveraged to functionally annotate the translated proteins. Downstream features include fast similarity search across three repositories, protein domain assignment, orthologous gene family assessment, and Gene Ontology term assignment. The final annotation integrates across multiple databases and selects an optimal assignment from a combination of weighted metrics describing similarity search score, taxonomic relationship, and informativeness. Researchers have the option to include additional filters to identify and remove contaminants, identify associated pathways, and prepare the transcripts for enrichment analysis. This fully featured pipeline is easy to install, configure, and runs significantly faster than comparable annotation packages. EnTAP is optimized to generate extensive functional information for the gene space of organisms with limited or poorly characterized genomic resources.

bioinformatics↗

bioRxiv2017

Dengue modeling in rural Cambodia: statistical performance versus epidemiological relevance

Dengue dynamics are shaped by the complex interplay between several factors, including vector seasonality, interaction between four virus serotypes, and inapparent infections. However, paucity or quality of data do not allow for all of these to be taken into account in mathematical models. In order to explore separately the importance of these factors in models, we combined surveillance data with a local-scale cluster study in the rural province of Kampong Cham (Cambodia), in which serotypes and asymptomatic infections were documented. We formulate several mechanistic models, each one relying on a different set of hypotheses, such as explicit vector dynamics, transmission via asymptomatic infections and coexistence of several virus serotypes. Models are confronted with the observed time series using Bayesian inference, through Markov chain Monte Carlo. Model selection is then performed using statistical information criteria, but also by studying the coherence of epidemiological characteristics (reproduction numbers, incidence proportion, dynamics of the susceptible class) in each model. Considering the available data, our analyses on transmission dynamics in a rural endemic setting highlight both the importance of using two-strain models with interacting effects and the lack of added value of incorporating vector and explicit asymptomatic components.

epidemiology↗

bioRxiv2017

High fidelity detection of crop biomass QTL from low-cost imaging in the field

Above-ground biomass production is a key target for studies of crop abiotic stress tolerance, disease resistance and yield improvement. However, biomass is slow and laborious to evaluate in the field using traditional destructive methods. High-throughput phenotyping (HTP) is widely promoted as a potential solution that can rapidly and non-destructively assess plant traits by exploiting advances in sensor and computing technology. A key potential application of HTP is for quantitative genetics studies that identify loci where allelic variation is associated with variation in crop production. And, the value of performing such studies in the field, where environmental conditions match that of production farming, is recognized. To date, HTP of biomass productivity in field trials has largely focused on expensive and complex methods, which - even if successful - will limit their use to a subset of wealthy research institutions and companies with extensive research infrastructure and highly-trained personnel. Even with investment in ground vehicles, aerial vehicles and gantry systems ranging from thousands to millions of dollars, there are very few examples where Quantitative trait loci (QTLs) detected by HTP of biomass production in a field-grown crop are shown to match QTLs detected by direct measures of biomass traits by destructive harvest techniques. Until such proof of concept for HTP proxies is generated it is unlikely to replace existing technology and be widely adopted. Therefore, there is a need for methods that can be used to assess crop performance by small teams with limited training and at field sites that are remote or have limited infrastructure. Here we use an inexpensive and simple, miniaturized system of hemispherical imaging and light attenuation modeling to identify the same set of key QTLs for biomass production as traditional destructive harvest methods applied to a field-grown Setaria mapping population. This provides a case study of a HTP technology that can deliver results for QTL mapping without high costs or complexity.

plant biology↗