Biology subjects

Novosadova, V.

Publications and source records attributed to Novosadova, V..

5 recordsLinked to original sources

bioRxiv2026

Automated Retinal Dysplasia Segmentation in Mouse Optical Coherence Tomography Scans Using a UNet-Based model

PurposeOptical coherence tomography (OCT) is the state-of-the-art non-invasive imaging technique for preclinical retinopathy studies. However, manual pathology annotations in mouse OCT scans are labour-intensive and susceptible to inter-rater variability. To alleviate these issues, we developed a neural network-based model for automated annotation of retinal dysplasia in mouse OCT scans. MethodsOur model was trained on 205 expert-annotated OCT stacks and validated on 40 unseen stacks with additional expert annotation comparisons in a subset of them. ResultsThe model detects pathologies with high accuracy (F1-score > 0.95) and consistency with experts (median Dice score > 0.8). We integrated the model into a cross-platform app ("OCTOPUS") that includes batch processing, automated annotation, manual annotation editing, and quantitative longitudinal tracking with pathological area estimation on the fundus image, and exportable results in CSV and SVG formats. ConclusionsOur open-source tool aims to facilitate and standardise OCT assessments between laboratories for efficient preclinical screening and high-throughput phenotyping in mouse models of retinal disease.

bioinformatics↗

bioRxiv2025

Post-transcriptional control of enamel matrix mineralization by TENT5A-mediated cytoplasmic polyadenylation

Tooth enamel formation, or amelogenesis, is a complex biomineralization process regulated by ameloblasts cells. These cells secrete enamel matrix proteins (EMPs), including Amelogenin (AMELX) and Ameloblastin (AMBN), which are essential for hydroxyapatite crystal deposition during enamel mineralization. Precise regulation of this process ensures the mechanical and chemical strength of dental enamel. Using Tent5a knock-out (KO) mouse, we demonstrated that TENT5A, a non-canonical poly(A) polymerase is crucial for the stability, translation, and secretion of EMP mRNAs, particularly AMELX, during amelogenesis. TENT5A-deficient mice exhibited Amelogenesis imperfecta, characterized by enamel hypomineralization, reduced thickness, and disrupted ultrastructure, as revealed by micro-computed tomography. Through nanopore direct mRNA sequencing, we identified that TENT5A polyadenylates Amelx and other mRNAs encoding secreted proteins, enhancing their stability and translation in the endoplasmic reticulum. Moreover, loss of TENT5A altered AMELX secretion and extracellular self-assembly, impairing matrix organization and hydroxyapatite deposition. This study highlights the role of TENT5A in post-transcriptional regulation during enamel formation, demonstrating its importance in enamel homeostasis. TeaserTENT5A adds poly(A) tails to specific mRNAs in enamel, enhancing their expression, which is crucial for dental mineralization.

developmental biology↗

bioRxiv2025

FAM83H regulates postnatal T cell development through thymic stroma organization

Family of Sequence Similarity 83H (FAM83H/ SACK1H) is primarily expressed in epithelial cells, where it interacts with casein kinase 1 (CK1) and keratins to regulate cytoskeletal organization, cell proliferation, and vesicular trafficking. Mutations in FAM83H are known to cause amelogenesis imperfecta, highlighting its critical role in enamel formation. We generated Fam83h-deficient mice (Fam83hem2(IMPC)Ccpcz, Fam83h-/-) and mice lacking a part of the N-terminal CK1-binding domain (Fam83h{Delta}87/{Delta}87). Consistent with other Fam83h-deficient models, these mice are subviable, smaller in size, and exhibit a sparse, scruffy coat, scaly skin, general weakness, and hypoactivity. Notably, both strains show impaired lymphoid cell development in early postnatal life. In the thymus, Fam83h expression is confined to thymic epithelial cells (TECs), and its deficiency in stromal cells results in disrupted thymic architecture and severe block in the expansion of DN3 (double-negative stage 3) T cells, ultimately leading to insufficient T cell production. Single-cell transcriptomic analysis reveals that Fam83h-/- cortical TECs (cTECs) express reduced levels of the TEC master regulator Foxn1, and its multiple downstream target genes, suggesting a critical role for FAM83H likely in coordination with CK1in cTEC maturation. HighlightsFam83h-deficient mice exhibit multiple epithelial defects, but no obvious enamel defects Fam83h deficiency disrupts lymphocyte development Fam83h deficiency impairs thymic epithelial cell maturation and thymus function

immunology↗

bioRxiv2019

Human and mouse essentiality screens as a resource for disease gene discovery

Although genomic sequencing has been transformative in the study of rare genetic diseases, identifying causal variants remains a considerable challenge that can be addressed in part by new gene-specific knowledge. Here, we integrate measures of how essential a gene is to supporting life, as inferred from the comprehensive viability and phenotyping screens performed on knockout mice by the International Mouse Phenotyping Consortium and from human cell line essentiality screens. We propose a novel, cross-species gene classification across the Full Spectrum of Intolerance to Loss-of-function (FUSIL) and demonstrate that genes in five mutually exclusive FUSIL categories have differing characteristics in the biological processes they regulate, tissue expression levels and human mutation rates. Most notably, Mendelian disease genes, particularly those associated with developmental disorders, are highly overrepresented in the developmental lethal category, representing genes not essential for cell survival but required for organism development. Exploiting this finding, we have screened developmental disorder cases from three independent disease sequencing consortia and identified potentially pathogenic, de novo variants shared in different patients for several developmental lethal genes that have not previously been associated with rare disease. We therefore propose FUSIL as an efficient resource for disease gene discovery.

genomics↗

bioRxiv2018

Rapid single-cell cytometry data visualization with EmbedSOM

Efficient unbiased data analysis is a major challenge for laboratories handling large cytometry datasets. We present EmbedSOM, a non-linear embedding algorithm based on FlowSOM that improves the analyses by providing high-performance visualization of complex single cell distributions within cellular populations and their transition states. The algorithm is designed for linear scaling and speed suitable for interactive analyses of millions of cells without downsampling. At the same time, the visualization quality is competitive with current state-of-art algorithms. We demonstrate the properties of EmbedSOM on workflows that improve two essential types of analyses: The native ability of EmbedSOM to align population positions in embedding is used for comparative analysis of multi-sample data, and the connection to FlowSOM is exploited for simplifying the supervised hierarchical dissection of cell populations. Additionally, we discuss the visualization of the trajectories between cellular states facilitated by the local linearity of the embedding.

bioinformatics↗