Department of Computer Science, Stanford University, 353 Serra Mall, Stanford, CA 94305, USA.
Bioinformatics. 2013 Jul 1;29(13):i18-26. doi: 10.1093/bioinformatics/btt223.
Advances in high-resolution microscopy have recently made possible the analysis of gene expression at the level of individual cells. The fixed lineage of cells in the adult worm Caenorhabditis elegans makes this organism an ideal model for studying complex biological processes like development and aging. However, annotating individual cells in images of adult C.elegans typically requires expertise and significant manual effort. Automation of this task is therefore critical to enabling high-resolution studies of a large number of genes.
In this article, we describe an automated method for annotating a subset of 154 cells (including various muscle, intestinal and hypodermal cells) in high-resolution images of adult C.elegans. We formulate the task of labeling cells within an image as a combinatorial optimization problem, where the goal is to minimize a scoring function that compares cells in a test input image with cells from a training atlas of manually annotated worms according to various spatial and morphological characteristics. We propose an approach for solving this problem based on reduction to minimum-cost maximum-flow and apply a cross-entropy-based learning algorithm to tune the weights of our scoring function. We achieve 84% median accuracy across a set of 154 cell labels in this highly variable system. These results demonstrate the feasibility of the automatic annotation of microscopy-based images in adult C.elegans.
高分辨率显微镜的最新进展使得分析单个细胞水平的基因表达成为可能。秀丽隐杆线虫(Caenorhabditis elegans)成年蠕虫中固定的细胞谱系使其成为研究发育和衰老等复杂生物学过程的理想模型。然而,对成年秀丽隐杆线虫图像中的单个细胞进行注释通常需要专业知识和大量的人工努力。因此,该任务的自动化对于实现对大量基因进行高分辨率研究至关重要。
在本文中,我们描述了一种自动注释成年秀丽隐杆线虫高分辨率图像中 154 个细胞(包括各种肌肉、肠和皮下细胞)子集的方法。我们将图像内的细胞标记任务表述为组合优化问题,其目标是最小化评分函数,该函数根据各种空间和形态特征,将测试输入图像中的细胞与手动注释的训练图谱中的细胞进行比较。我们提出了一种基于最小成本最大流的方法来解决这个问题,并应用基于交叉熵的学习算法来调整我们的评分函数的权重。在这个高度可变的系统中,我们在 154 个细胞标签中实现了 84%的中位数准确性。这些结果证明了在成年秀丽隐杆线虫中基于显微镜图像的自动注释的可行性。