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Mohsin, A.

Publications and source records attributed to Mohsin, A..

2 recordsLinked to original sources

FiberAI: A Deep Learning model for automated analysis of nascent DNA Fibers

All life forms undergo cell division and are dependent on faithful DNA replication to maintain the stability of their genomes. Both intrinsic and extrinsic factors can stress the replication process and multiple checkpoint mechanisms have evolved to ensure genome stability. Understanding these molecular mechanisms is crucial for preventing and treating genomic instability associated diseases including cancer. DNA replicating fiber fluorography is a powerful technique that directly visualizes the replication process and a cells response to replication stress. Analysis of DNA-fiber microscopy images provides quantitative information about replication fitness. However, a bottleneck for high throughput DNA-fiber studies is that quantitative measurements are laborious when performed manually. Here we introduce FiberAI, which uses state-of-the art deep learning frameworks to detect and quantify DNA-fibers in high throughput microscopy images. FiberAI efficiently detects DNA fibers, achieving a bounding box average precision score of 0.91 and a segmentation average precision score of 0.90. We then use FiberAI to measure the integrity of replication checkpoints. FiberAI is publicly available and allows users to view model predicted selections, add their own manual selections, and easily analyze multiple image sets. Thus, FiberAI can help elucidate DNA replication processes by streamlining DNA-fiber analyses.

bioinformatics

In situ humoral selection in human lupus tubulointerstitial inflammation

ABSTRACTIn human lupus nephritis, tubulointerstitial inflammation (TII) is associated with in situ expansion of B cells expressing anti-vimentin antibodies (AVAs). The mechanism by which AVAs are selected is unclear. Herein, we demonstrate that AVA somatic hypermutation and selection increase affinity for vimentin. However, enzyme-linked immunosorbent assays (ELISAs) suggested that affinity maturation might be a non-specific consequence of increasing polyreactivity. Subsequent multi-color confocal microscopy studies indicated that while TII AVAs often appeared polyreactive by ELISA, they bound selectively to vimentin fibrils in whole cells or inflamed renal tissue. Using a novel machine learning pipeline (CytoSkaler) to quantify the cellular distribution of antibody staining, we demonstrated that TII AVAs were selected for both enhanced binding and specificity in situ. These data suggest a new approach to assess and define antibody polyreactivity based on quantifying the distribution of binding to native and contextually relevant antigens.Competing Interest StatementThe authors have declared no competing interest.View Full Text

immunology