Biology subjects

Has, C.

Publications and source records attributed to Has, C..

4 recordsLinked to original sources

bioRxiv2026

Synthetic-data augmented calibration for expert-informed rare disease models

Clinical data for rare diseases are sparse, noisy, and heterogeneous, complicating calibration of ordinary differential equation (ODE) models. Thus, we introduce a noise-robust calibration in latent space that combines expertderived ODEs with learned latent representations. Our approach leverages synthetic ODE trajectories, augmenting our scarce observations to train a model-specific autoencoder representation and imputer. During calibration, observed and ODE-generated trajectories are compared in latent space, and ODE parameters are updated by minimizing their latent distance. In a controlled ABCDE simulation model, the imputer outperformed a carry-forward baseline for moderate parameter shifts, parameter recovery remained stable under random missingness, calibration remained robust to additional noise variables despite reduced downstream identifiability, and distinct dynamics formed visually separable latent trajectories. On a custom developed ODE model for real Epidermolysis Bullosa patients, the calibrated phenomenological model reproduced patient-level trajectories from sparse observations. Thus, we conclude that our latent-space calibration approach supports rare-disease modeling.

bioinformatics↗

bioRxiv2023

Lipidome unsaturation affects the morphology and proteome of the Drosophila eye.

While the proteome of an organism is largely determined by the genome, the lipidome is shaped by a poorly understood interplay of environmental factors and metabolic processes. To gain insights into the underlying mechanisms, we analyzed the impacts of dietary lipid manipulations on the ocular proteome of Drosophila melanogaster. We manipulated the lipidome with synthetic food media that differed in the supplementation of an equal amount of saturated or polyunsaturated triacylglycerols. This allowed us to generate flies whose eyes had a highly contrasting length and unsaturation of glycerophospholipids, the major lipid class of biological membranes, while the abundance of other membrane lipid classes remained unchanged. By bioinformatically comparing the resulting ocular proteomic trends and contrasting them with the impacts of vitamin A deficiency, we identified ocular proteins whose abundances are differentially affected by lipid saturation and unsaturation. For instance, we unexpectedly identified a group of proteins that have muscle-related functions and increase their abundances in the eye upon lipidome unsaturation but are unaffected by lipidome saturation. Moreover, we identified two differentially lipid-responsive proteins involved in stress responses, Turandot A and Smg5, whose abundances decrease with lipid unsaturation. Lastly, we discovered that the ocular lipid class composition is robust to dietary changes and propose that this may be a general homeostatic feature of the organization of eukaryotic tissues, while the length and unsaturation of fatty acid moieties is more variable to compensate environmental challenges. We anticipate that these insights into the molecular responses of the Drosophila eye proteome to specific lipid manipulations will guide the genetic dissection of the mechanisms that maintain visual function when the eye is exposed to dietary challenges.

neuroscience↗

bioRxiv2023

Eye proteome of Drosophila melanogaster

The Drosophila melanogaster eye is a popular model to elucidate the molecular mechanisms that underlie the structure and function of the eye as well as the causes of retinopathies. For instance, the Drosophila eye has been used to investigate the impacts of ageing and environmental stresses such as light-induced damage or dietary deficiencies. Moreover, large-scale screens have isolated genes whose mutation causes morphological and functional ocular defects, which includes key components of the phototransduction cascade. However, the proteome of the Drosophila eye is poorly characterized. Here, we used GeLC-MS/MS to quantify 3516 proteins he adult Drosophila melanogaster eye and provide a generic and expandable resource for further genetic, pharmacological, and dietary studies.

neuroscience↗

bioRxiv2017

Boron Hyperaccumulation Mechanisms in Puccinellia distans as Revealed by Transcriptomic Analysis

Boron is an essential plant micronutrient; but is toxic at high concentrations. Boron toxicity can severely affect crop productivity in arid and semi-arid environments. Puccinellia distans (Jacq.) Par1., common alkali grass, is found throughout the world and can survive under boron concentrations that are lethal for other plant species. In addition, P. distans can accumulate very high levels of this element. Despite these interesting features, very little research has been performed to elucidate the boron tolerance mechanism in this species. In this study, P. distans samples were analyzed by RNA sequencing to identify genes related to boron tolerance and hyperaccumulation. Abundance levels of selected differentially expressed transcripts were validated by real-time PCR. The results indicated that the hyperaccumulation mechanism of P. distans involves many transcriptomic changes including those that lead to: alterations in the malate pathway, changes in cell wall components that allow sequestration of excess boron without toxic effects, and increased expression of at least one putative boron transporter and two putative aquaporins. Elucidation of the boron accumulation mechanism is important to develop approaches for bioremediation of boron contaminated soils.

plant biology↗