Eli Lilly and Company, Indianapolis, IN, United States of America.
School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore, Singapore.
PLoS One. 2024 Sep 20;19(9):e0310157. doi: 10.1371/journal.pone.0310157. eCollection 2024.
The complexity of branching and curvilinear morphology of a complete mitochondrial network within each cell is challenging to analyze and quantify. To address this challenge, we developed an image analysis technique using persistent homology with a multiparameter filtration framework, combining image processing techniques in mathematical morphology. We show that such filtrations contain both topological and geometric information about complex cellular organelle structures, which allows a software program to extract meaningful features. Using this information, we also develop a connectivity index that describes the morphology of the branching patterns. As proof of concept, we utilize this approach to study how mitochondrial networks are altered by genetic changes in the Optineurin gene. Mutations in the autophagy gene Optineurin (OPTN) are associated with primary open-angle glaucoma (POAG), amyotrophic lateral sclerosis (ALS), and Paget's disease of the bone, but the pathophysiological mechanism is unclear. We utilized the proposed mathematical morphology-based multiparameter filtration and persistent homology approach to analyze and quantitatively compare how changes in the OPTN gene alter mitochondrial structures from their normal interconnected, tubular morphology into scattered, fragmented pieces.
完整线粒体网络在每个细胞内的分支和曲线形态的复杂性使得分析和量化变得具有挑战性。为了解决这个挑战，我们开发了一种使用持久同调的图像分析技术，结合数学形态学中的图像处理技术，建立了一个多参数过滤框架。我们表明，这种过滤既包含了关于复杂细胞细胞器结构的拓扑和几何信息，也允许软件程序提取有意义的特征。利用这些信息，我们还开发了一个连接性指数来描述分支模式的形态。作为概念验证，我们利用这种方法来研究 Optineurin 基因的遗传变化如何改变线粒体网络。自噬基因 Optineurin (OPTN) 的突变与原发性开角型青光眼 (POAG)、肌萎缩性侧索硬化症 (ALS) 和骨 Paget 病有关，但病理生理机制尚不清楚。我们利用所提出的基于数学形态学的多参数过滤和持久同调方法来分析和定量比较 OPTN 基因的变化如何将线粒体结构从正常的相互连接的管状形态改变为分散的、碎片化的形态。
