Biology subjects

Fraser, M.

Publications and source records attributed to Fraser, M..

12 recordsLinked to original sources

bioRxiv2025

Ancestry, admixture, and pathogens in contemporaneous Neolithic farmers and foragers on the Island of Gotland

Two archaeological cultural complexes coexisted on Gotland for over 500 years, between [~]3300 and 2800 calBCE, i.e. the Neolithic Funnelbeaker culture (FBC), and the Pitted ware culture (PWC). The ancestry of the FBC farmers and PWC marine foragers largely aligns with European Neolithic Farmers and European Mesolithic foragers, respectively, but the direct interactions between the groups on Gotland is not understood. We present a Middle Neolithic (MN) high-coverage genome and a Late Neolithic (LN) low-coverage genome from the Ansarve FBC dolmen. We investigate ancestry, admixture, and pathogens among these MN farmers (n =6), foragers (n=19), and a LN individual. We find that recent gene-flow between farmers and foragers could have taken place, although most gene-flow happened prior to their coexistence on the island. We also find evidence of different Yersinia pestis strains in the three cultural groups, showing that the pestis was widespread among groups with different subsistence strategies.

genomics↗

bioRxiv2025

Reading ability in both deaf and hearing adults is linked to neural representations of abstract phonology derived from visual speech

Reading is central to academic and vocational success. Some deaf children face reading challenges due to limited access to spoken or signed language. Robust phonological representations are key to reading development in hearing children. Spoken language phonology may be one of many contributors to reading development in deaf children. Indeed, speechreading ability correlates with reading skill in both deaf and hearing individuals, suggesting it is linked to reading development regardless of hearing status. Further support for this hypothesis would be provided by evidence that similar neural representations of speech phonology are evoked by visual speech and other language forms (auditory speech and text), and that these neural representations are related to reading proficiency. We used fMRI and Representational Similarity Analysis (RSA) to identify shared neural representations of spoken language phonological structure. A group of deaf adult participants (N=22), with a mixture of sign language and spoken language backgrounds and reading abilities, were presented with single lexical items as visual speech and dynamic text (cursive text, revealed letter-by-letter to promote a phonological reading strategy). Adult hearing participants (N=25) were presented with the same words, but as visual speech and auditory speech. Shared neural representations of phonological structure of English words were found in each group in the superior and middle temporal cortex (STC/MTC) and these abstract representations were more similar across different language forms in better readers. Our data provide neurobiological evidence of the contribution of visual speech to abstract phonological representations of spoken language, that relate to reading proficiency, in both deaf and hearing adults. Significance StatementReading is an essential skill, yet some deaf children face reading challenges due to reduced access to signed or spoken language. In hearing children, successful reading depends on abstract phonological representations, but whether spoken language phonology relates to reading in deaf individuals remains unclear. Using fMRI and RSA, we show that deaf and hearing adults recruit neural representations of phonology that are shared by visual speech and other language forms (visual/auditory speech in hearing; visual speech/dynamic text in deaf) in the superior and middle temporal cortex. Critically, greater cross-modal alignment of neural representations of phonological structure was associated with better reading in both groups. These findings provide neurobiological evidence that visual speech contributes to phonological representations that relate to reading, regardless of hearing status.

neuroscience↗

bioRxiv2025

The Landscape of Prostate Tumour Methylation

Prostate cancer is characterized by profound clinical and molecular heterogeneity. While its genomic heterogeneity is well-characterized, its epigenomic heterogeneity remains less understood. We therefore created a compendium of 3,001 multi-ancestry prostate methylomes spanning normal tissue through localized disease of all grades to poly-metastatic disease. A subset of 884 samples had multi-omic DNA and/or RNA characterization. We identify four epigenomic subtypes that risk-stratify patients and reflect distinct evolutionary trajectories. We demonstrate extensive regulatory interplay between DNA copy number and methylation, with transcriptional consequences that vary across genes and disease stages. We define epigenetic dysregulation signatures for 15 important clinico-molecular features, creating predictive models for each. For example, we identify specific epigenetic features that predict patient outcome and are synergistic with clinical prognostic features. These results define a complex interplay between tumour genetics and epigenetics that converges to modify gene-expression programs and clinical presentation, in part through modulation of epigenetic aging.

cancer biology↗

bioRxiv2022

Landscape-scale exposure to multiazole-resistant Aspergillus fumigatus bioaerosols

We demonstrate country-wide exposures to aerosolized spores of a human fungal pathogen, Aspergillus fumigatus, that has acquired resistance to first line azole clinical antifungal drugs. Assisted by a network of citizen scientists across the United Kingdom, we show that 1 in 20 viable aerosolized spores of this mold are resistant to the agricultural fungicide tebuconazole and 1 in 140 spores are resistant to the four most used azoles for treating clinical aspergillosis infections. Season and proximity to industrial composters were associated with growth of A. fumigatus from air samples, but not with the presence of azole resistance, and hotspots were not stable between sampling periods suggesting a high degree of atmospheric mixing. Genomic analysis shows no distinction between those resistant genotypes found in the environment and in patients, indicating that ~40% (58/150 sequenced genomes) of azole-resistant A. fumigatus infections are acquired from environmental exposures. Due to the ubiquity of this measured exposure, it is crucial that we determine source(s) of azole-resistant A. fumigatus, who is at greatest risk of exposure and how to mitigate these exposures, in order to minimize treatment failure in patients with aspergillosis. One sentence summaryUK-wide citizen science surveillance finds a ubiquitous exposure to aerosolized spores of a human fungal pathogen that have evolved in the environment cross-resistance to essential clinical antifungal drugs

microbiology↗

bioRxiv2021

Modelling the collective mechanical regulation of the structure and morphology of epithelial cell layers

The morphology and function of epithelial sheets play an important role in healthy tissue development and cancer progression. The maintenance of structure of closely packed epithelial layers requires the coordination of various mechanical forces within the cells and others resulting from interactions with other cells and other tissues or substrates. However, a general model for the combination of mechanical properties which determine the cell shape and the overall structure of epithelial layers remains elusive. Here, we propose a computational model, based on the Cellular Potts Model, to study the interplay between mechanical properties of cells and dynamical transitions in epithelial structures and cell shapes. We map out phase diagrams as functions of cellular properties and the orientation of cell division. Monolayers of squamous, cuboidal, and columnar cells are found when the axis of cell proliferation is perpendicular to the substrate. Monolayer-to-multilayer transition is promoted via cell extrusion, depending on the mechanical properties of cells and the orientation of cell division. The results and model predictions are discussed in the context of experimental observations.

biophysics↗

bioRxiv2021

Development of the Wheat Practical Haplotype Graph Database as a Resource for Genotyping Data Storage and Genotype Imputation

To improve the efficiency of high-density genotype data storage and imputation in bread wheat (Triticum aestivum L.), we applied the Practical Haplotype Graph (PHG) tool. The wheat PHG database was built using whole-exome capture sequencing data from a diverse set of 65 wheat accessions. Population haplotypes were inferred for the reference genome intervals defined by the boundaries of the high-quality gene models. Missing genotypes in the inference panels, composed of wheat cultivars or recombinant inbred lines genotyped by exome capture, genotyping-by-sequencing (GBS), or whole-genome skim-seq sequencing approaches, were imputed using the wheat PHG database. Though imputation accuracy varied depending on the method of sequencing and coverage depth, we found 93% imputation accuracy with 0.01x sequence coverage, which was only slightly lower than the accuracy obtained using the 0.5x sequence coverage (96.9%). Compared to Beagle, on average, PHG imputation was ~4% (p-value = 0.00027) more accurate, and showed 27% higher accuracy at imputing a rare haplotype introgressed from a wild relative into wheat. The reduced accuracy of imputation with GBS data (90.4%) is likely associated with the small overlap between GBS markers and the exome capture dataset, which was used for constructing PHG. The highest imputation accuracy was obtained with exome capture for the wheat D genome, which also showed the highest levels of linkage disequlibrium and proportion of identity-by-descent regions among accessions in our reference panel. We demonstrate that genetic mapping based on genotypes imputed using PHG identifies SNPs with a broader range of effect sizes that together explain a higher proportion of genetic variance for heading date and meiotic crossover rate compared to previous studies.

genomics↗

bioRxiv2021

The Telomere Length Landscape of Localized Prostate Cancer

Replicative immortality is a hallmark of cancer, and can be achieved through telomere lengthening and maintenance. We report telomere lengths (TLs) of 392 localized prostate cancer tumours and characterize their relationship to genomic, transcriptomic and proteomic features. Shorter tumour TLs were associated with elevated genomic instability, including single-nucleotide variants, indels and structural variants. Genes involved in cell proliferation and signaling were correlated with tumour TL at all levels of the central dogma. TL was also associated with multiple clinical features of a tumour. Longer TLs in non-tumour samples were associated with a lower rate of biochemical relapse after definitive local therapy. Our analysis integrates multi-omics data to illuminate the relationship of specific genomic alterations in a tumour and TL in prostate cancer. Although the role of telomere length in cancer has been well studied, its association to genomic features is less well known. We describe the multi-level integration of telomere length, genomics, transcriptomics and proteomics in localized prostate cancer. Patient Summary We examined the association between telomere length and multiple omics-level data in prostate cancer. We observed that traditional telomere mutations are rare in prostate cancer and that telomere length is associated with multiple measure of genomic instability.

genomics↗

bioRxiv2021

Cis-Regulatory Element Hijacking by Structural Variants Overshadows Topological Changes in Primary Prostate Cancer

Prostate cancer is a heterogeneous disease whose progression is linked to genome instability. However the impact of this instability on the three-dimensional chromatin organization and how this drives progression is unclear. Using primary benign and tumour tissue, we find a high concordance in the higher-order three-dimensional genome organization across normal and prostate cancer cells. This concordance argues for constraints to the topology of prostate tumour genomes. Nonetheless, we identify changes to focal chromatin interactions and show how structural variants can induce these changes to guide cis-regulatory element hijacking. Such events result in opposing differential expression on genes found at antipodes of rearrangements. Collectively, our results argue that cis-regulatory element hijacking from structural variant-induced altered focal chromatin interactions overshadows higher-order topological changes in the development of primary prostate cancer.

cancer biology↗

bioRxiv2020

Only two out of five articles by New Zealand researchers are free-to-access: a multiple API study of access, its impact on open citation advantage, cost of Article Processing Charges (APC), and the potential to increase the proportion of open access

We studied journal articles published by researchers at all eight of New Zealand universities in 2017 to determine how many were freely accessible on the web. We wrote software code to harvest data from multiple sources, code that we now share to enable others to reproduce our work on their own sample set. In May 2019, we ran our code to determine which of the 2017 articles were open at that time and by what method; where those articles would have incurred an Article Processing Charge (APC) we calculated the cost if those charges had been paid. Where articles were not freely available we determined whether the policies of publishers in each case would have allowed deposit in a non-commercial repository (Green open access). We also examined citation rates for different types of access. We found that, of our 2017 sample set, about two out of every five articles were freely accessible without payment or subscription (41%). Where research was explicitly said to be funded by New Zealands major research funding agencies, the proportion was slightly higher at 45%. Where open articles would have incurred an APC we estimated an average cost per article of USD1,682 (for publications where all articles require an APC, that is, Gold open access) and USD2,558 (where APC payment is optional, Hybrid open access) at a total estimated cost of USD1.45m. Of the paid options, Gold is by far more common for New Zealand researchers (82% Gold, 18% Hybrid). In terms of citations, our analysis aligned with previous studies that suggest a correlation between publications being freely accessible and, on balance, slightly higher rates of citation. This is not seen across all types of open access, however, with Diamond OA achieving the lowest rates. Where articles were not freely accessible we found that a very large majority of them (88% or 3089 publications) could have been legally deposited in an institutional repository. Similarly, only in a very small number of cases had a version deposited in the repository of a New Zealand university made the difference between the publication being freely accessible or not (125 publications). Given that most New Zealand researchers support research being open, there is clearly a large gap between belief and practice in New Zealands research ecosystem.

scientific communication and education↗

bioRxiv2020

Temporal hierarchy converges with spatial hierarchy: Intrinsic neural timescales follow core-periphery organization

The human cortex exhibits intrinsic neural timescales that shape a temporal hierarchy. Whether this temporal hierarchy follows the spatial hierarchy of its topography namely the core-periphery organization remains an open issue. Using Magnetoencephalography data, we investigate intrinsic neural timescales during rest and task states; we measure the autocorrelation window in short (ACW-50) and, introducing a novel variant, long (ACW-0) windows. We demonstrate longer ACW-50 and ACW-0 in networks located at the core compared to those at the periphery with rest and task states showing a high ACW correlation. Calculating rest-task differences, i.e., subtracting the shared core-periphery organization, reveals task-specific ACW changes in distinct networks. Finally, employing kernel density estimation, machine learning, and simulation, we demonstrate that ACW-0 exhibits better prediction in classifying a regions time window as core or periphery. Overall, our findings provide fundamental insight into how the human cortexs temporal hierarchy converges with its spatial core-periphery hierarchy.

neuroscience↗

bioRxiv2018

Valection: Design Optimization for Validation and Verification Studies

BackgroundPlatform-specific error profiles necessitate confirmatory studies where predictions made on data generated using one technology are additionally verified by processing the same samples on an orthogonal technology. In disciplines that rely heavily on high-throughput data generation, such as genomics, reducing the impact of false positive and false negative rates in results is a top priority. However, verifying all predictions can be costly and redundant, and testing a subset of findings is often used to estimate the true error profile. To determine how to create subsets of predictions for validation that maximize inference of global error profiles, we developed Valection, a software program that implements multiple strategies for the selection of verification candidates.\n\nResultsTo evaluate these selection strategies, we obtained 261 sets of somatic mutation calls from a single-nucleotide variant caller benchmarking challenge where 21 teams competed on whole-genome sequencing datasets of three computationally-simulated tumours. By using synthetic data, we had complete ground truth of the tumours mutations and, therefore, we were able to accurately determine how estimates from the selected subset of verification candidates compared to the complete prediction set. We found that selection strategy performance depends on several verification study characteristics. In particular the verification budget of the experiment (i.e. how many candidates can be selected) is shown to influence estimates.\n\nConclusionsThe Valection framework is flexible, allowing for the implementation of additional selection algorithms in the future. Its applicability extends to any discipline that relies on experimental verification and will benefit from the optimization of verification candidate selection.

bioinformatics↗

bioRxiv2017

Genomics of Mesolithic Scandinavia reveal colonization routes and high-latitude adaptation

Scandinavia was one of the last geographic areas in Europe to become habitable for humans after the last glaciation. However, the origin(s) of the first colonizers and their migration routes remain unclear. We sequenced the genomes, up to 57x coverage, of seven hunter-gatherers excavated across Scandinavia and dated to 9,500-6,000 years before present. Surprisingly, among the Scandinavian Mesolithic individuals, the genetic data display an east-west genetic gradient that opposes the pattern seen in other parts of Mesolithic Europe. This result suggests that Scandinavia was initially colonized following two different routes: one from the south, the other from the northeast. The latter followed the ice-free Norwegian north Atlantic coast, along which novel and advanced pressure-blade stone-tool techniques may have spread. These two groups met and mixed in Scandinavia, creating a genetically diverse population, which shows patterns of genetic adaptation to high latitude environments. These adaptations include high frequencies of low pigmentation variants and a gene-region associated with physical performance, which shows strong continuity into modern-day northern Europeans.

genomics↗