Biology subjects

Attar, S.

Publications and source records attributed to Attar, S..

3 recordsLinked to original sources

bioRxiv2026

Multimodal analysis of molecular remodeling in aging spleen identified global and cell type specific changes

Aging reshapes the cellular and molecular landscape of mammalian tissues. These changes can be progressive, preceding linearly with age, or occur as abrupt transitions of the course of lifespan. To investigate the age-dependent cellular and molecular shifts we profiled matched proteomes and transcriptomes from male and female murine spleens across eight time points, from stable adults through late life. The spleen was chosen to integrate understanding of age-dependent changes associated with immune surveillance, inflammaging, and immune-related proteostasis. Male and female mice follow distinct aging trajectories particularly in protein-RNA correlation in late life, reflecting both compositional shifts and failure of post-transcriptional buffering. To investigate whether these changes could be attributed to specific cell-types within the spleen, we developed Celestial, a machine-learning framework to identify cell-type-specific changes in bulk tissue samples. We found that age-related bulk molecular changes could be attributed in part to compositional remodeling of cell-types--expansion of GZMK+ CD8+ T cells and C1Q+ macrophages alongside naive T cell and global B cell loss. These results demonstrate that cell-type-aware interpretation can inform bulk multi-omic data for accurate mechanistic inference in heterogeneous tissues undergoing complex molecular remodeling.

systems biology↗

bioRxiv2023

Programmable peroxidase-assisted signal amplification enables flexible detection of nucleic acid targets in cellular and histopathological specimens

In situ hybridization (ISH) is a powerful tool for investigating the spatial arrangement of nucleic acid targets in fixed samples. ISH is typically visualized using fluorophores to allow high sensitivity and multiplexing or with colorimetric labels to facilitate co-visualization with histopathological stains. Both approaches benefit from signal amplification, which makes target detection effective, rapid, and compatible with a broad range of optical systems. Here, we introduce a unified technical platform, termed pSABER, for the amplification of ISH signals in cell and tissue systems. pSABER decorates the in situ target with concatemeric binding sites for a horseradish peroxidase-conjugated oligonucleotide which can then catalyze the massive localized deposition of fluorescent or colorimetric substrates. We demonstrate that pSABER effectively labels DNA and RNA targets, works robustly in cultured cells and challenging formalin fixed paraffin embedded (FFPE) specimens. Furthermore, pSABER can achieve 25-fold signal amplification over conventional signal amplification by exchange reaction (SABER) and can be serially multiplexed using solution exchange. Therefore, by linking nucleic acid detection to robust signal amplification capable of diverse readouts, pSABER will have broad utility in research and clinical settings.

genomics↗

bioRxiv2020

PaintSHOP enables the interactive design of transcriptome- and genome-scale oligonucleotide FISH experiments

Fluorescent in situ hybridization (FISH) allows researchers to visualize the spatial position and quantity of nucleic acids in fixed samples. Recently, considerable progress has been made in developing oligonucleotide (oligo)-based FISH methods. These methods have enabled researchers to study the three-dimensional organization of the genome at super-resolution and visualize the spatial patterns of gene expression for thousands of genes in individual cells. While considerable progress has been made in developing new molecular methods that harness complex oligo libraries for FISH, there are few existing computational tools to support the bioinformatics workflows necessary to carry out these experiments. Here, we introduce Paint Server and Homology Optimization Pipeline (PaintSHOP), an interactive platform for the reproducible design of oligo FISH experiments. PaintSHOP enables researchers to identify probes for their experimental targets efficiently, to incorporate additional necessary sequences such as primer pairs, and to easily generate standardized files documenting the design of their libraries. Our platform integrates a machine learning model that quantitatively predicts probe specificity on the genome scale into a dynamic web application that creates ready-to-order probe sets for a wide variety of applications. The goal of this freely available web resource is to democratize and standardize the process of designing complex probe sets for the oligo FISH community. PaintSHOP can be accessed at: paintshop.ioCompeting Interest StatementThe authors have declared no competing interest.View Full Text

genomics↗