Biology subjects

Davis, W.

Publications and source records attributed to Davis, W..

3 recordsLinked to original sources

bioRxiv2024

A hybrid machine learning model for predicting gene expression from epigenetics across fungal species

Understanding gene expression is crucial for optimizing biological processes in bioeconomic processes, human health, and environmental regulation. Epigenetic modifications significantly influence gene expression by altering chromatin structure and DNA accessibility. However, knowledge about the conservation of these mechanisms across species, especially in non-model organisms, is limited. This study predicts gene expression levels based on epigenetic modifications across fungal species, facilitating knowledge transfer from well-characterized to less understood species. We developed a deep learning model, MAPLE (Model predictions Across Phylogenetic distances by Learning Expression from Epigenetics), which integrates convolutional layers and multi-head attention to capture dependencies in epigenetic data. MAPLE shows strong cross-species performance in fungi, achieving up to 80% accuracy and 89% AUROC for intra-species validation, and 77% accuracy and 83% AUROC in cross-species tasks, outperforming benchmarks. SHAP analysis reveals key epigenetic features driving gene expression, providing insights for future experimental design. Our findings highlight MAPLEs potential to generalize across fungal species, offering a versatile tool for optimizing gene expression.

systems biology↗

bioRxiv2022

Integrative metabolomics reveal the organisation of alkaloid biosynthesis in Daphniphyllum macropodum

Daphniphyllum alkaloids are structurally diverse nitrogen-containing compounds with polycyclic, stereochemically rich carbon skeletons. Understanding how plants biosynthesise these compounds may lead to greater access to allow exploration of bioactivities; however, very little is known about their biosynthetic origins. Here, we integrated metabolomics approaches to map alkaloid distribution across Daphniphyllum macropodum plants and tissues. We generated a novel untargeted metabolomics workflow to highlight trends in alkaloid distribution across tissues, using a holistic approach that does not rely on ambiguous peak annotations. Both liquid-chromatography-mass spectrometry and mass-spectrometry imaging analyses independently revealed that alkaloids have a pattern of spatial distribution based on their skeletal subtypes. The distinct alkaloid subtype localisation suggests the biosynthetic pathway is controlled spatially with intermediates transported from the phloem to the epidermis where they undergo additional derivatization. This study sets the stage for the future work on Daphniphyllum alkaloid biosynthesis and highlights how integrating different metabolomics strategies can reveal valuable insights on these compounds distribution within the plant.

plant biology↗

bioRxiv2019

Endocytosis of very low-density lipoprotein particles: an unexpected mechanism for lipid acquisition by breast cancer cells

We previously described the expression of CD36 and lipoprotein lipase (LPL) by breast cancer (BC) cells and tissues, and the growth-promoting effect of very low-density lipoprotein (VLDL) supplementation observed in BC cell lines only in the presence of LPL. We now describe the deployment of LPL by BC cells. Our data support a model in which LPL is bound to a heparin-like heparan sulfate proteoglycan motif on the BC cell surface and acts in concert with the VLDL receptor to rapidly internalize intact lipoproteins via receptor-mediated endocytosis. We further observe substantial alterations in gene expression programs related to pathways for lipid acquisition (synthesis vs. uptake) in response to each the availability of exogenous triglyceride in tissue culture media and LPL expression status. Current literature emphasizes de novo fatty acid synthesis as the paramount mechanism for lipid acquisition by cancer cells. Our findings indicate that exogenous lipid uptake can serve as an important method of lipid acquisition for cancer cells, alongside de novo lipogenesis, and that the relative reliance on these two modes of lipid acquisition may vary among different BC cell lines and in response to nutrient availability. This concept has obvious implications for the development of therapies aimed at the lipid dependence of many different cancer types. Moreover, the mechanism that we have elucidated provides a direct connection between dietary fat and tumor biology.

cancer biology↗