Biology subjects

Price, B.

Publications and source records attributed to Price, B..

7 recordsLinked to original sources

bioRxiv2025

KODAMA enables self-guided weakly supervised learning in spatial transcriptomics

Spatial transcriptomics provides researchers with a powerful tool to investigate gene expression patterns within their native positional context in tissues, revealing intricate cellular relationships. However, analyzing spatial transcriptomics data presents unique challenges due to their high dimensionality and complexity. Several competitive tools have emerged, each aiming to integrate spatial dependencies into their workflow. Yet, the overall performance of these approaches remains constrained by limitations in prediction accuracy and compatibility with specific data types. Here, we introduce the third version of the KODAMA algorithm, specifically tailored for spatial transcriptomics analysis. This upgraded version incorporates a novel approach that effectively reduces data dimensionality while preserving spatial information. At its core, the KODAMA algorithm employs parallel iterations that enforce spatial constraints throughout an embedded clustering process. Our method provides the flexibility to simultaneously analyze multiple samples, streamlining analysis workflows. Additionally, it extends beyond traditional 2D analysis to accommodate multidimensional datasets, including 3D spatial information. KODAMA seamlessly integrates into various pipelines, such as Seurat and Giotto. Extensive evaluations of KODAMA on 10x Visium, Visium HD, and image-based 3D datasets demonstrate its high accuracy in spatial domain prediction. Comparative analyses against alternative dimensionality reduction techniques and spatial analysis tools consistently validate and highlight KODAMAs superior performance in unraveling the spatial organization of cellular components across both single and integrated tissue samples.

bioinformatics↗

bioRxiv2022

Comparing the accuracy and efficiency of third generation DNA barcode sequencing: Oxford Nanopore Technologies versus Pacific Biosciences

At times of drastic decrease in biodiversity and loss of species, sometimes referred to as the "sixth mass extinction" or "Holocene extinction", there is a high demand on the development of effective tools for studying and monitoring biodiversity. In the past decade, new promising technologies, such as third generation sequencing (TGS), enabled massive, rapid, and cost-effective data analysis of non-model organisms, accelerating taxonomic identification studies and contributing to conservation applications. Here, we focus on the comparison of the two main TGS providers, Pacific Biosciences (PacBio), and Oxford Nanopore Technologies (ONT), for the purpose of DNA barcoding. For ONT, we also tested selected combinations of different types of flow cells and ligation sequencing kits. Out of five tested combinations (PacBio, ONT Flongle flow cell & SQK-LSK110 kit, R9 flow cell & SQK-LSK109 kit, R9 & SQK-LSK100 kit, and R10 flow cell & Q20+ chemistry kit), ONTs Flongle turned out to be most variable in returning the results, but at the same time the most cost efficient. The highest numbers of successfully sequenced samples were achieved with the ONTs R10 & Q20+ chemistry combination. In terms of library preparation time, ONT protocols are the quickest, whereas regarding cost effectiveness - using Sanger pricing per sample as a cut-off - various technologies become affordable depending on the number of samples used. Although both tested platforms are suitable for DNA barcoding, we further discuss their limitations and applicability to different studies, with a special focus on the price and the number of samples. The pipeline we developed, from whole specimens to final DNA barcode consensuses, can aid planning and budgeting biodiversity studies, maximising the number of specimens sequenced in one run and speeding up the sample processing time.

molecular biology↗

bioRxiv2022

An Integrated Model for Predicting KRAS Dependency

BackgroundThe clinical approvals of KRAS G12C inhibitors has been a revolutionary advance in precision oncology, but response rates are often modest. To improve patient selection, we developed an integrated model to predict KRAS dependency. Methods and FindingsBy integrating molecular profiles of a large panel of cell lines from the DEMETER2 dataset, we built a binary classifier to predict a tumors KRAS dependency. Monte Carlo cross validation via ElasticNet within the training set was used to compare model performance and to tune parameters. The final model was then applied to the validation set. We validated the model with genetic depletion assays and an external dataset of lung cancer cells treated with a G12C inhibitor. We then applied the model to several Cancer Genome Atlas (TCGA) datasets. The final "K20" model contains 20 features, including expression of 19 genes and KRAS mutation status. In the validation cohort, K20 had an AUC of 0.94 and accurately predicted KRAS dependency in both mutant and KRAS wild-type cell lines following genetic depletion. It was also highly predictive across an external dataset of lung cancer lines treated with KRAS G12C inhibition. When applied to TCGA datasets, specific subpopulations such as the invasive subtype in colorectal cancer and copy number high pancreatic adenocarcinoma were predicted to have higher KRAS dependency. ConclusionThe K20 model has simple yet robust predictive capabilities that may provide a useful tool to select patients with KRAS mutant tumors that are most likely to respond to direct KRAS inhibitors.

bioinformatics↗

bioRxiv2021

Immunogenicity of an AAV-based, room-temperature stable, single dose COVID-19 vaccine in mice and non-human primates

The SARS-CoV-2 pandemic has affected more than 70 million people worldwide and resulted in over 1.5 million deaths. A broad deployment of effective immunization campaigns to achieve population immunity at global scale will depend on the biological and logistical attributes of the vaccine. Here, two adeno-associated viral (AAV)-based vaccine candidates demonstrate potent immunogenicity in mouse and nonhuman primates following a single injection. Peak neutralizing antibody titers remain sustained at 5 months and are complemented by functional memory T-cells responses. The AAVrh32.33 capsid of the AAVCOVID vaccine is an engineered AAV to which no relevant pre-existing immunity exists in humans. Moreover, the vaccine is stable at room temperature for at least one month and is produced at high yields using established commercial manufacturing processes in the gene therapy industry. Thus, this methodology holds as a very promising single dose, thermostable vaccine platform well-suited to address emerging pathogens on a global scale.

immunology↗

bioRxiv2020

A rapid urban biodiversity blitz using aquatic environmental DNA

Background As global biodiversity declines, there’s an increasing need to create an educated and engaged society. Having people from all ages participate in measuring biodiversity where they live helps to create awareness. Recently, the use of environmental DNA (eDNA) for biodiversity surveys has gained momentum. Here, we test whether sampling eDNA and metabarcoding can be used for rapid urban biodiversity surveys for educational purposes.Materials & Methods We sampled 2×1 L of water from each of 15 locations in the city of Trondheim, Norway, including a variety of freshwater, marine and brackish habitats. DNA was extracted, amplified in triplicate for the COI gene and sequenced. The obtained data were analysed on the novel mBRAVE platform, an online open access software and computing resource.Results The water samples were collected in two days by two people and the lab analysis was completed in five days by one person. Overall, we detected the presence of 501 taxa identified as belonging to 435 species, representing 90 orders and 18 phyla. On average, only 5.4% of the taxa were shared among six replicates per site. Based on the observed diversity, three distinct clusters were detected and related to geographic distribution of sites. There were some taxa shared between the habitats, with a substantial presence of terrestrial biota.Discussion Our results match expected patterns of biodiversity in the landscape and show that with minimal sampling effort, hundreds of species can be detected. Thus, using eDNA analysis of water is promising for rapid biodiversity surveys, and it is likely that more detailed results could be obtained by optimising field and lab methods for particular groups of interest. We recommend that rapid eDNA surveys, with openly available services and softwares, can be used to raise awareness in the importance of biodiversity.Competing Interest StatementThe authors have declared no competing interest.View Full Text

scientific communication and education↗

bioRxiv2019

Metabarcoding unsorted kick-samples facilitates macroinvertebrate-based biomonitoring with increased taxonomic resolution, while outperforming environmental DNA

Many studies have highlighted the potential of DNA-based methods for the biomonitoring of freshwater macroinvertebrates, however only a few studies have investigated homogenisation of bulk samples that include debris to reduce sample-processing time. In order to explore the use of DNA-based methods in water quality assessment in South Africa, this study compares morphological and molecular-based identification of freshwater macroinvertebrates at the mixed higher taxon and mOTU level while investigating abundance and comparing mOTU recovery with historical species records. From seven sites across three rivers in South Africa, we collected a biomonitoring sample, an intensive-search comprehensive sample and an eDNA sample per site. The biomonitoring sample was picked and scored according to standard protocols and the leftover debris and comprehensive samples were homogenised including all debris. DNA-based methods recovered higher diversity than morphology, but did not always recover the same taxa, even at the family level. Regardless of the differences in taxon scores, most DNA-based methods except some eDNA samples, returned the same water quality assessment category as the standard morphology-based assessment. Homogenised comprehensive samples recovered more freshwater invertebrate diversity than all other methods. The eDNA samples recovered 2 to 10 times more mOTUs than any other method, however 90% of reads were non-target and as a result eDNA recovered the lowest target diversity. However, eDNA did find some target taxa that the other methods failed to detect. This study shows that unsorted samples recover the same water quality scores as a morphology-based assessment and much higher diversity scores than both picked and eDNA samples. As a result, there is potential to integrate DNA-based approaches into existing metrics quickly while providing much more information for the development of more refined metrics at the species or mOTU level with distributional data which can be used for conservation and biodiversity management.

ecology↗

bioRxiv2019

Evaluating the relationships between the legal and illegal international wildlife trades

The international legal trade in wildlife can provide economic and other benefits, but when unsustainable can be a driver of population declines. This impact is enhanced by the additional burden of illegal trade. We combined law-enforcement time-series of seizures of wildlife goods imported into the United States (US) and the European Union (EU) with data on reported legal trade to evaluate the evidence for any relationships. Our analysis examined 28 (US) and 20 (EU) taxon-products with high volume and frequency of reported trade and seizures. On average, seizures added 28% and 9% to US and EU reported legal trade levels respectively, and in several cases exceeded legal imports. We detected a significant but weak overall positive relationship between seizure volumes and reported trade imported to the US over time, but none in the EU. Our findings suggest a complex and nuanced temporal association between the illegal and legal wildlife trades.

ecology↗