Biology subjects

Johnson, M. L.

Publications and source records attributed to Johnson, M. L..

5 recordsLinked to original sources

bioRxiv2024

A novel HLA Class II presentation prediction algorithm deciphers immunogenic CD4 epitopes specific to KRAS G12C

Accurate prediction of peptide presentation by HLA molecules is important for generation of effective individualized cancer vaccines and immunotherapies. While presentation prediction algorithms for HLA class I have been successfully applied in the context of such therapies, improved prediction algorithms for class II are needed. EDGE-II is a novel algorithm based on a protein large language model that has a learned allele deconvolution network trained on existing and new immunopeptidomics data. It delivers state-of-the-art performance on prediction of peptide presentation by HLA class II and immunogenicity elicited by CD4+ T-cell epitopes. In a patient with a KRAS G12C positive tumor treated with a KRAS G12C targeting immunotherapy, EDGE-II identified KRAS G12C class II neoantigens that elicited clonally expanded CD4+ T cells with cytotoxic transcriptional profiles post-vaccination. EDGE-II could play an important role in the development of effective cancer immunotherapies by elucidating an enriched understanding of the immunopeptidome.

bioinformatics↗

bioRxiv2024

Allele Sails: launching traits and fates into wild populations with DNA sequence modifiers

Population-scale genome editing can be used to alter the composition or fate of wild populations. One approach to achieving these aims utilizes a synthetic gene drive element--a multi-gene cassette--to bring about an increase in the frequency of an existing allele. However, the use of gene drives is complicated by the multiple scientific, regulatory, and social issues associated with transgene persistence and gene flow. Alternatives in which transgenes are not driven could potentially avoid some of these issues. Here we propose an approach to population scale gene editing using a system we refer to as an Allele Sail. An Allele Sail consists of a genome editor (the Wind) that introduces DNA sequence edits (the Sail) at one or more sites, resulting in progeny that are viable and fertile. The editor, such as a sequence-specific nuclease, or a prime- or base-editor, is inherited in a Mendelian fashion. Meanwhile, the edits it creates experience an arithmetic, Super-Mendelian increase in frequency. We explore this system using agent-based modeling, and identify contexts in which a single, low frequency release of an editor brings edits to a very high frequency. We also identify conditions in which manipulation of sex determination can be used to bring about population suppression. Current regulatory frameworks often distinguish between transgenics as genetically modified organisms (GMOs), and their edited non-transgenic progeny as non-GMO. In this context an Allele Sail provides a path to alter traits and fates of wild populations in ways that may be considered more acceptable.

synthetic biology↗

bioRxiv2022

DNA metabarcoding reveals the dietary profiles of a benthic marine crustacean, Nephrops norvegicus

Norwegian lobster, Nephrops norvegicus, are a generalist scavenger and predator capable of short foraging excursions but can also suspension feed. Existing knowledge about their diet relies on a combination of methods including morphology-based stomach content analysis and stable isotopes, which often lack the resolution to distinguish prey items to species level particularly in species that thoroughly masticate their prey. DNA metabarcoding overcomes many of the challenges associated with traditional methods and it is an attractive approach to study the dietary profiles of animals. Here, we present the diet of the commercially valuable Nephrops norvegicus using DNA metabarcoding of gut contents. Despite difficulties associated with host amplification, our cytochrome oxidase I (COI) molecular assay successfully achieves higher resolution information than traditional approaches. We detected taxa that were likely consumed during different feeding strategies. Dinoflagellata, Chlorophyta and Bacillariophyta accounted for almost 50% of the prey items consumed, and are associated with suspension feeding, while fish with high fisheries discard rates were detected which are linked to active foraging. In addition, we were able to characterise biodiversity patterns by considering Nephrops as natural samplers, as well as detecting parasitic dinoflagellates (e.g., Hematodinium sp.), which are known to influence burrow related behaviour in infected individuals in over 50% of the samples. The metabarcoding data presented here greatly enhances a better understanding of a species ecological role and could be applied as a routine procedure in future studies for proper consideration in the management and decision-making of fisheries.

ecology↗

bioRxiv2022

High-latitude marginal reefs support fewer but bigger corals than their tropical counterparts

AimDespite the awareness that climate change impacts are typically detrimental to tropical coral reefs, the effect of increasing environmental stress and variability on the population size structure of coral species remains poorly understood. This gap in knowledge limits our ability to effectively conserve coral reef ecosystems because size specific dynamics are rarely incorporated. Our aim is to quantify variation in the size structure of coral populations along a tropical-to-subtropical environmental gradient. Location20 coral populations along a latitudinal gradient on the east coast of Australia ([~]23{degrees}S to 30{degrees}S). Time PeriodBetween 2010 and 2018. Major taxa studiedScleractinian corals. MethodsWe apply two methods to quantify the relationship between environmental covariates and coral population size structure along a latitudinal environmental gradient. First, we use linear regression with summary statistics, such as median size as response variables; a method frequently favoured by ecologists. The second method is compositional functional regression, a novel method using entire size-frequency distributions as response variables. We then predict coral population size structure with increasing environmental stress and variability. ResultsCompared to tropical reefs, we find fewer but larger coral colonies in marginal reefs, where environmental conditions are more variable and stressful for corals in the former. Our model predicts that coral populations may become gradually dominated by larger colonies (> 148 cm2) with increasing environmental stress. Main conclusionsWith increasing environmental stress and variability, we can expect shifts in coral population size structure towards more larger colonies. Fewer but bigger corals suggest low survival, slow growth, and poor recruitment. This finding is concerning for the future of coral reefs as it implies populations may have low recovery potential from disturbances. We highlight the importance and usefulness of continuously monitoring changes to population structure over large spatial scales. Data availabilityData is supplied in the supplementary information, or upon request. Once accepted for publication it will be made openly available on Dryad.

ecology↗

bioRxiv2018

Genome wide association analysis identifies genetic variants associated with reproductive variation across domestic dog breeds and uncovers links to domestication

The diversity of eutherian reproductive strategies has led to variation in many traits, such as number of offspring, age of reproductive maturity, and gestation length. While reproductive trait variation has been extensively investigated and is well established in mammals, the genetic loci contributing to this variation remain largely unknown. The domestic dog, Canis lupus familiaris is a powerful model for studies of the genetics of inherited disease due to its unique history of domestication. To gain insight into the genetic basis of reproductive traits across domestic dog breeds, we collected phenotypic data for four traits - cesarean section rate (n = 97 breeds), litter size (n = 60), stillbirth rate (n = 57), and gestation length (n = 23) - from primary literature and breeders handbooks. By matching our phenotypic data to genomic data from the Cornell Veterinary Biobank, we performed genome wide association analyses for these four reproductive traits, using body mass and kinship among breeds as co-variates. We identified 14 genome-wide significant associations between these traits and genetic loci, including variants near CACNA2D3 with gestation length, MSRB3 with litter size, SMOC2 with cesarean section rate, MITF with litter size and still birth rate, KRT71 with cesarean section rate, litter size, and stillbirth rate, and HTR2C with stillbirth rate. Some of these loci, such as CACNA2D3 and MSRB3, have been previously implicated in human reproductive pathologies. Many of the variants that we identified have been previously associated with domestication-related traits, including brachycephaly (SMOC2), coat color (MITF), coat curl (KRT71), and tameness (HTR2C). These results raise the hypothesis that the artificial selection that gave rise to dog breeds also shaped the observed variation in their reproductive traits. Overall, our work establishes the domestic dog as a system for studying the genetics of reproductive biology and disease.

evolutionary biology↗