Biology subjects

Carter, E. J.

Publications and source records attributed to Carter, E. J..

11 recordsLinked to original sources

bioRxiv2026

geoGraph: Connectivity modelling across geographic space with hexagonal discrete global grids

1. Estimating the movement and connectivity of organisms across landscapes is central to research in ecology and evolutionary biology. Although graph-based approaches representing geographic space as weighted networks provide a flexible and computationally efficient framework for such analyses, existing tools either perform their computations only on rectangular raster grids, thus introducing systematic directional and area distortions at global scales, or rely on bespoke pipelines that limit the general applicability of recent hexagonal-grid analyses. 2. To overcome these shortcomings, here we present geoGraph, an R package that brings graph-based spatial modelling to discrete global hexagonal grids. By representing landscapes on an equal-area hexagonal tessellation of the sphere, geoGraph enables global-scale analysis without projection distortion while retaining the flexibility of the graph framework and the performance of the graph and RBGL/Boost libraries. The package integrates both raster- and vector-based GIS data into a single cost surface, supports custom grids at various resolutions, and provides a complete pipeline from raw GIS layers to graph-algorithmic outputs, together with tools for visualising and interactively editing graphs. 3. We illustrate geoGraph by revisiting previous studies of isolation by distance among human populations in the Human Genome Diversity Project panel. At a global scale, restricting movement to land raised the correlation between geographic and genetic distance from r = 0.74 (great-circle) to r = 0.84. On a finer grid within Asia, accounting for terrain ruggedness improved the fit, with the best-fitting models implying reduced movement across the Himalaya and Tibetan Plateau. These analyses demonstrate that geoGraph can model movement and connectivity appropriate to the desired spatial scale and that the level of geographic realism required is itself scale-dependent. 4. By combining discrete global grids with the power of graph algorithms, geoGraph enables seamless connectivity analysis from landscape to global scales. It is broadly applicable across landscape genetics, phylogeography, conservation planning, and studies of human dispersal, and is particularly suited to large-scale problems that rectangular-raster tools cannot address without distortion.

bioinformatics↗

bioRxiv2026

Fine-scale population structure within and among Malagasy societies

The population of Madagascar exhibits a globally unique combination of African and Asian genetic ancestries. Previous studies have described the admixture history of Madagascar at island-wide scales [1,2], but less focus has been paid to fine-scale population structure across the island. We present new genome-wide genetic data from 192 individuals sampled across five regions of Madagascar. We identify population structure at extremely fine spatial scales ([~]10 km) among the Merina of the central highlands. By analysing subpopulations separately, we found one Merina group exhibited similarity to coastal populations in f4 ratios, estimated admixture dates, and pairwise FST distances, while another group was similar to other highland individuals in the same measures. This fine-scale substructure is likely associated with historical coastal-to-highland migration during the 18th and 19th centuries. In contrast, we also observe macro-scale structure in estimated timing of admixture across the island, with southeastern coastal groups exhibiting the earliest estimated admixture timings, and northern groups exhibiting the latest. This pattern corroborates previous results [1,2], and may suggest differing histories of admixture timing among Malagasy populations. Our results emphasise the importance of deep micro-geographic sampling to complement macro-scale analysis when characterising demographic history.

genetics↗

bioRxiv2025

Design and Evaluation of PLGA-Based Nanocarriers for Targeted and Sustained Drug Delivery in Vascular Disorders

Vascular diseases, including atherosclerosis and vascular inflammation, have high incidence and mortality rates worldwide. Current drug therapies are limited by short circulation time, broad non-specific distribution, insufficient efficacy, and significant side effects. This study aimed to develop and optimize a targeted nanodrug delivery system based on poly(lactic-co-glycolic acid) (PLGA) to improve drug accumulation and therapeutic outcomes at vascular lesion sites. Nanoparticles prepared by the solvent evaporation-self-assembly method had an average diameter of 145.6 {+/-} 12.3 nm, a zeta potential of -21.4 {+/-} 3.7 mV, and showed uniform spherical morphology. The encapsulation efficiency (EE%) was 82.3 {+/-} 4.5%, and the drug loading (DL%) was 9.6 {+/-} 1.1%, indicating good drug-carrying ability. For surface modification, conjugation of ligands to the ends of PEG chains balanced the conflict between "stealth" and "affinity," maintaining circulation stability while restoring effective binding to vascular endothelial cells. Drug release experiments demonstrated a biphasic release profile in PBS (pH 7.4): about 40% was released within 0-12 h, and cumulative release reached 76.5 {+/-} 3.2% at 72 h. Kinetic analysis fitted the Higuchi model (R2 = 0.983), suggesting diffusion as the main driving mechanism. This predictable and controllable release behavior can provide both rapid effect in the acute phase and sustained therapy in the chronic phase. Overall, the PLGA nanocarrier system proposed in this study showed clear advantages in physicochemical properties, surface functionalization, and drug release kinetics. It can achieve prolonged circulation, high targeting efficiency, and controlled release in the treatment of vascular diseases. This work provides experimental evidence to overcome the limitations of conventional drug therapy and lays the foundation for developing multifunctional and clinically translatable nanodrug delivery platforms for personalized treatment.

bioengineering↗

bioRxiv2025

tidygenclust: Clustering for Population Genetics in R

BackgroundPopulation structure analysis is crucial for evolutionary research and medical genomics. Clustering methods, broadly categorized as model-based (e.g. ADMIXTURE) or non-model-based (e.g. SCOPE), differ in their methodology and computational efficiency. Recently, fastmixture, a model-based approach, has improved scalability and performance, while replicate alignment tools, such as Clumppling, extend previous methods by also aligning the modes across K values. However, all the existing tools are standalone and generate numerous untracked text files, as well as offering limited plot customisability. ResultsWe introduce an R package, tidygenclust, which brings the functionalities of the original ADMIXTURE, fastmixture and Clumppling software into R, enabling a streamlined and integrated workflow. By integrating with tidypopgen, a package designed to handle large SNP datasets, these new tools maintain metadata, simplify data handling, and produce results as customisable ggplot2 objects for flexible visualisation. ConclusionsThe R package tidygenclust advances population genetic analysis by combining computational efficiency with reproducible workflows and user-friendly plotting. The source code and instructions can be accessed on https://github.com/EvolEcolGroup/tidygenclust.

bioinformatics↗

bioRxiv2025

tidypopgen: Tidy Population Genetics in R

As genome-wide data has become increasingly available, software libraries for their analysis have proliferated. While new tools for downstream analyses are constantly emerging, existing workflows are hindered by inefficiencies. Switching between coding languages and object types in the early stages of pipelines wastes researchers time, impedes reproducibility, and creates opportunity for error. To confront these obstacles, we introduce tidypopgen, a comprehensive R package for population genetic analysis of biallelic SNP data. Genotype data can be read, filtered, and analysed within a single environment, without the need for prior data cleaning or setup with other software. tidypopgens gen_tibble object structure makes analysis efficient and intuitive, while standardised tidy grammar makes data manipulation clear. Functionality within tidypopgen supports cleaning and merging datasets, basic descriptive statistics, multivariate analysis, clustering algorithms, and F-statistics, as well as integrating with existing tools for population genetic analyses in R. We use the Human Genome Diversity Project SNP dataset (Li et al., 2008) to show that a basic population genetic workflow can be executed in under 25 lines of code in a single environment using one file set, without the need to write superfluous outputs or change directories. By supporting data assembly through to data analysis, tidypopgen significantly streamlines workflows without compromising speed or functionality.

bioinformatics↗

bioRxiv2023

Visualizing the chaperone-mediated folding trajectory of the G protein β5 β-propeller

The cytosolic Chaperonin Containing Tailless polypeptide 1 (CCT) complex is an essential protein folding machine with a diverse clientele of substrates, including many proteins with {beta}- propeller domains. Here, we determined structures of CCT in complex with its accessory co chaperone, phosducin-like protein 1 (PhLP1), in the process of folding G{beta}5, a component of Regulator of G protein Signaling (RGS) complexes. Cryo-EM and image processing revealed an ensemble of distinct snapshots that represent the folding trajectory of G{beta}5 from an unfolded molten globule to a fully folded {beta}-propeller. These structures reveal the mechanism by which CCT directs G{beta}5 folding through initiating specific intermolecular contacts that facilitate the sequential folding of individual {beta}-sheets until the propeller closes into its native structure. This work directly visualizes chaperone-mediated protein folding and establishes that CCT directs folding by stabilizing intermediates through interactions with surface residues that permit the hydrophobic core to coalesce into its folded state.

biochemistry↗

bioRxiv2021

Xist-mediated silencing requires additive functions of SPEN and Polycomb together with differentiation-dependent recruitment of SmcHD1

X chromosome inactivation (XCI) is mediated by the non-coding RNA Xist which directs chromatin modification and gene silencing in cis. The RNA binding protein SPEN and associated corepressors have a central role in Xist-mediated gene silencing. Other silencing factors, notably the Polycomb system, have been reported to function downstream of SPEN. In recent work we found that SPEN has an additional role in correct localisation of Xist RNA in cis, indicating that its contribution to chromatin-mediated gene silencing needs to be reappraised. Making use of a SPEN separation-of-function mutation we show that SPEN and Polycomb pathways in fact function in parallel to establish gene silencing. Additionally, we find that differentiation-dependent recruitment of the chromosomal protein SmcHD1 is required for silencing many X-linked genes. Our results provide important insights into the mechanism of X inactivation and the coordination of chromatin-based gene regulation with cellular differentiation and development.

molecular biology↗

bioRxiv2020

HIV coinfection is associated with low fitness rpoB variants in rifampicin-resistant Mycobacterium tuberculosis

We analysed 312 drug-resistant genomes of Mycobacterium tuberculosis (Mtb) collected from HIV coinfected and HIV negative TB patients from nine countries with a high tuberculosis burden. We found that rifampicin-resistant Mtb strains isolated from HIV coinfected patients carried disproportionally more resistance-conferring mutations in rpoB that are associated with a low fitness in the absence of the drug, suggesting these low fitness rpoB variants can thrive in the context of reduced host immunity.

evolutionary biology↗

bioRxiv2019

Mortality among adults living with HIV treated for tuberculosis based on positive, negative, or no bacteriologic test results for tuberculosis: the IeDEA consortium

BackgroundIn resource-constrained settings, people living with HIV (PLWH) treated for tuberculosis (TB) despite negative bacteriologic tests have a higher mortality than those treated with positive tests. Many PLWH are treated without bacteriologic testing; their mortality compared to those with bacteriologic testing is uncertain.\n\nMethodsWe conducted an observational cohort study among PLWH [≥] 15 years of age who initiated TB treatment at clinical sites affiliated with four regions of the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium from 2012-2014: Caribbean, Central and South America, and Central, East, and West Africa. The primary exposure of interest was the TB bacteriologic test status at TB treatment initiation: positive, negative, or no test result. The hazard for death in the 12 months following TB treatment initiation was estimated using the Cox proportional hazard model, adjusted for patient- and site-level factors. Missing covariates were multiply imputed.\n\nResultsAmong 2,091 PLWH included, the median age at TB treatment initiation was 36 years, 44% were female, 53% had CD4 counts [≤] 200 cells/mm3, and 52% were on antiretroviral treatment (ART). Compared to patients with positive bacteriologic tests, the adjusted hazard for death was higher among patients with no test results (HR 1.56, 95% CI 1.08-2.26) but not different than those with negative tests (HR 1.28, 95% CI 0.91-1.81). Older age was also associated with a higher hazard for death, while being on ART, having a higher CD4 count, West Africa region, and tertiary facility level were associated with lower hazards for death.\n\nConclusionPLWH treated for TB with no bacteriologic test results were more likely to die than those treated with positive tests, underscoring the importance of TB bacteriologic diagnosis in resource-constrained settings. Research is needed to understand the causes of death among PLWH treated for TB in the absence of positive bacteriologic tests.

epidemiology↗

bioRxiv2018

Systematic Allelic Analysis Defines the Interplay of Key Pathways in X Chromosome Inactivation

Xist RNA, the master regulator of X chromosome inactivation, acts in cis to induce chromosome silencing through the stepwise recruitment of factors that modify underlying chromatin structure. Whilst considerable progress has been made towards defining key silencing factors and the elements to which they bind, their relative contribution to silencing different genes, and their relationship with one another is poorly understood. Here we describe a systematic analysis of Xist-mediated allelic silencing in ES cell-based models. We show that Spen, recruited through the Xist A-repeat, plays a central role, being critical for silencing of all except a subset of weakly expressed genes. Polycomb, recruited through the Xist B/C-repeat, also plays a key role, favouring silencing of genes with pre-existing H3K27me3 chromatin. LBR and the Rbm15/ m6A-methyltransferase complex, previously proposed to have a central role, make at most a minor contribution to gene silencing. We integrate our findings in a comprehensive model for Xist-mediated chromosome silencing.

genetics↗

bioRxiv2018

Drug susceptibility testing and mortality in patients treated for tuberculosis in high-burden countries

BackgroundDrug resistance and HIV co-infection are challenges for the global control of tuberculosis.\n\nMethodsWe collected Mycobacterium tuberculosis isolates from adult patients in Cote dIvoire, Democratic Republic of the Congo, Kenya, Nigeria, South Africa, Peru, and Thailand, stratified by HIV status and tuberculosis drug resistance. Molecular or phenotypic drug susceptibility testing (DST) was done locally and at the Swiss tuberculosis reference laboratory. We examined mortality during treatment according to DST results and treatment adequacy in logistic regression models adjusting for sex, age, sputum microscopy and HIV status.\n\nFindings634 tuberculosis patients were included; median age was 33.2 years, 239 (37.7%) were female, 272 (42.9%) HIV-positive and 69 (10.9%) patients died. Based on the reference laboratory DST, 394 (62.2%) strains were pan-susceptible, 45 (7.1%) mono-resistant, 163 (25.7%) multidrug-resistant (MDR-TB), and 30 (4.7%) had pre-extensive or extensive drug resistance (pre-XDR/XDR-TB). Results of reference and local laboratories were discordant in 121 (19.1%) cases, corresponding to a sensitivity of 84.3% and a specificity of 90.8%. In patients with drug-resistant tuberculosis, discordant results were associated with increased mortality (risk ratio 1.81; 95% CI 1.07-3.07). In logistic regression, compared to adequately treated patients with pan-susceptible strains, the adjusted odds ratio for death was 4.23 (95% CI 2.16-8.29) for adequately treated patients with drug-resistant strains and 21.54 (95% CI 3.36-138.1) for inadequately treated patients with drug-resistant strains. HIV status was not associated with mortality.\n\nInterpretationUsing a reference laboratory standard, inaccurate DST leading to inappropriate treatment of drug-resistant tuberculosis, but not HIV infection, contributed to mortality.

epidemiology↗