category
bioRxiv
date
Mar 17, 2026
slug
status
Published
summary
开发基于视觉Transformer(ViT)的图像分类框架,通过kymographs图像分析线粒体运动特征,相比传统统计方法(如线粒体速度和静止比例)显著提升疾病表型分类准确率;利用生物重复验证模型稳健性,并通过ViT嵌入分析揭示线粒体大小变异和交叉事件与R364W突变的强关联性。
tags
基因编辑
type
Post

📄 原文题目

Using image classifiers to predict CMT2A disease-relevant mitochondrial motility phenotypes in iPSC motor neurons

🔗 原文链接

💡 AI 核心解读

开发基于视觉Transformer(ViT)的图像分类框架,通过kymographs图像分析线粒体运动特征,相比传统统计方法(如线粒体速度和静止比例)显著提升疾病表型分类准确率;利用生物重复验证模型稳健性,并通过ViT嵌入分析揭示线粒体大小变异和交叉事件与R364W突变的强关联性。

📝 英文原版摘要

Charcot-Marie-Tooth disease type 2A (CMT2A) is a genetic disease characterized by autosomal dominant MFN2 mutations and dysregulated mitochondrial trafficking. While there is currently no FDA-approved CMT2A therapy, the recent development of iPSC motor neuron model systems, high-throughput imaging platforms, and CRISPR-based gene editing technologies holds promise for screening new therapies at scale in vitro. A critical roadblock for therapeutic screening is the development of scalable and robust computational methods to assess the mitochondrial trafficking phenotypes, healthy or diseased, of each iPSC motor neuron sample. To address this gap, we developed a vision transformer (ViT) based classification framework that predicts disease phenotypes using kymographs, an image transformation that captures particle movement along a prespecified path, such as mitochondrial movement along axons. We show that our classification approach more accurately discriminates healthy MFN2 wild-type (WT) from diseased MFN2 R364W-mutant (R364W) iPSCs than alternative summary statistics, such as mitochondrial speed and fraction of stationary mitochondria that are directly extracted from kymographs. Furthermore, we show that our model maintains high accuracy when deployed on a biological replicate holdout dataset. An analysis of ViT patch embeddings of the kymographs shows that mitochondria with highly variable sizes and many intersection events most strongly associate with R364W diseased kymographs. The computational approach demonstrated in this paper has broad applicability for future high-throughput screens where organelle trafficking along axons plays a key role in disease pathogenesis.
自动化循环超分辨率显微镜用于纳米级蛋白质测绘抑制剂-2通过对接基序依赖的催化亚基向适配器转移指导PP1全酶的形成
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