Biology subjects

Lupo, M.

Publications and source records attributed to Lupo, M..

4 recordsLinked to original sources

bioRxiv2026

Crop-OCT: a Fully Integrated Imageomics Pipeline to Identify Regional and Focal Retinopathy in Murine Models

Imageomics uses machine learning to accelerate our understanding of biological traits and human disease processes. Some of the earliest imageomics applications used deep learning to assess human diseases. For example, retinal fundus images were analyzed to diagnose diabetic retinopathy. The imaging modality optical coherence tomography (OCT) is widely used to diagnose and monitor the progression of retinopathy in patients and preclinical models. The standardized instrumentation and image format of OCT lends itself to imageomics, but generalizable, automated pipelines for segmentation and quantitation of large numbers of OCT images are still in early development. Here, we present the automated, end-to-end pipeline Crop-OCT that extracts features from thousands of OCT images, while preserving their location within the eye. We used the Crop-OCT pipeline on a diverse dataset, including 13 genetic models of retinopathy, with more than 20,000 OCT images, which allowed us to analyze nearly 6 million measured features. The pipeline was generalized on an independent dataset that was analyzed in a blinded manner. The pipeline enabled us to monitor ocular changes associated with aging and progression of diseases, such as retinitis pigmentosa, Leber congenital amaurosis, achromatopsia, Stargardt disease, diabetic retinopathy, and age-related macular degeneration. We also characterized heterogeneity across animals and identified regional and focal lesions. Our pipeline will unify feature extraction for preclinical models of retinal disease and serve as a foundation for future multimodal data integration for artificial intelligence applications based on imageomics.

neuroscience↗

bioRxiv2024

A spatial cell atlas of neuroblastoma reveals developmental, epigenetic and spatial axis of tumor heterogeneity

Neuroblastoma is a pediatric cancer arising from the developing sympathoadrenal lineage with complex inter- and intra-tumoral heterogeneity. To chart this complexity, we generated a comprehensive cell atlas of 55 neuroblastoma patient tumors, collected from two pediatric cancer institutions, spanning a range of clinical, genetic, and histologic features. Our atlas combines single-cell/nucleus RNA-seq (sc/scRNA-seq), bulk RNA-seq, whole exome sequencing, DNA methylation profiling, spatial transcriptomics, and two spatial proteomic methods. Sc/snRNA-seq revealed three malignant cell states with features of sympathoadrenal lineage development. All of the neuroblastomas had malignant cells that resembled sympathoblasts and the more differentiated adrenergic cells. A subset of tumors had malignant cells in a mesenchymal cell state with molecular features of Schwann cell precursors. DNA methylation profiles defined four groupings of patients, which differ in the degree of malignant cell heterogeneity and clinical outcomes. Using spatial proteomics, we found that neuroblastomas are spatially compartmentalized, with malignant tumor cells sequestered away from immune cells. Finally, we identify spatially restricted signaling patterns in immune cells from spatial transcriptomics. To facilitate the visualization and analysis of our atlas as a resource for further research in neuroblastoma, single cell, and spatial-omics, all data are shared through the Human Tumor Atlas Network Data Commons at www.humantumoratlas.org.

cancer biology↗

bioRxiv2023

DNA actively contributes to gene expression of paired transcription factors.

The binding affinity of transcription factors (TFs) for their cognate DNA sequences controls gene expression. DNA determines the recruitment and positioning of TFs; whether it plays other roles is unknown. Here we found that the specific 22-bp sequence interposed between the CRX and NRL TFs in the proximal promoter of RHODOPSIN (RHO) largely controls the expression levels of RHO. Mutagenesis of this DNA-linker sequence resulted in wide variation in gene expression. In contrast, reciprocal exchange of human and murine RHO elements conferred species-specific expression levels. Targeting the DNA-linker with equal orthogonal DNA-binding proteins activates or represses RHO expression depending on its orientation relative to CRX and NRL binding sites. We conclude that DNA itself adds to TF activity through a code that determines optimal levels of RHO expression.

genetics↗

bioRxiv2018

The Nucleome of Developing Murine Rod Photoreceptors

The nuclei of rod photoreceptors in mice and other nocturnal species have an unusual inverted chromatin structure: the heterochromatin is centrally located to help focus light and improve photosensitivity. To better understand this unique nuclear organization, we performed ultra-deep Hi-C analysis on murine retina at 3 stages of development and on purified rod photoreceptors. Predicted looping interactions from the Hi-C data were validated with fluorescence in situ hybridization (FISH). We discovered that a subset of retinal genes that are important for retinal development, cancer, and stress response are localized to the facultative heterochromatin domain. We also used machine learning to develop an algorithm based on our chromatin Hidden Markov Modeling (chromHMM) of retinal development to predict heterochromatin domains and study their dynamics during retinogenesis. FISH data for 264 genomic loci were used to train and validate the algorithm. The integrated data were then used to identify a developmental stage- and cell type-specific core regulatory circuit super-enhancer (CRC-SE) upstream of the Vsx2 gene, which is required for bipolar neuron expression. Deletion of the Vsx2 CRC-SE in mice led to the loss of bipolar neurons in the retina.

neuroscience↗