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基于显微镜的高通量实验中的微妙细胞表型的自动定量

Automatic quantification of subtle cellular phenotypes in microscopy-based high-throughput experiments
课程网址: http://videolectures.net/mlsb2010_ljosa_aqs/  
主讲教师: Vebjorn Ljosa
开课单位: 麻省理工学院
开课时间: 2010-11-08
课程语种: 英语
中文简介:
基于显微镜的高通量实验可以观察单个细胞的生物反应和状态。Cellprofiler,我们的开源图像分析软件,已经被生物学家广泛用于设计复杂的高通量分析的自定义分析管道。我将讨论我们正在进行的自动量化培养细胞高通量样本中细微细胞表型的流行率的工作。我还将快速接触机器学习的使用,以提高细胞配置文件图像分割的准确性和鲁棒性。我们的分类工具Cellprofiler Analyst使生物学家能够反复训练一个增强分类器,以检测罕见的、复杂的表型,它的实用性已在多个高通量屏幕上得到证明。在这里,我将描述一种学习表型的方法,而不需要手工标记细胞进行训练。相反,在实验中,分类器是从阴性和阳性对照中训练出来的,即使只是轻微的(例如55%对45%的外显率),也知道阳性在感兴趣的表型中是丰富的。通过将单元非线性投影到随机特征空间中,我们可以使用有效的线性方法,但仍然受益于非线性相似概念,并且可以通过训练数百万个单元来克服实验噪声。使用产生的分类器将软标签分配给实验中的每个单元格,我们可以非参数地识别强化样本(";点击";)。此外,我们正在开发在大规模化学分析实验中自动识别相关细胞表型的技术。
课程简介: Microscopy-based high-throughput experiments can provide a view into biological responses and states at the resolution of singe cells. CellProfiler, our open-source image-analysis software, has become widely used by biologists to design custom analysis pipelines for complex high-throughput assays. I will discuss our work in progress to automatically quantify the prevalence of subtle cellular phenotypes in high-throughput samples of cultured cells I will also touch briedly on the use of machine learning to improve the accuracy and robustness of CellProfiler's image segmentation. Our classification tool, CellProfiler Analyst, enables a biologist to train a boosting classifier iteratively to detect rare, complex phenotypes, and its usefulness has been demonstrated in several high-throughput screens. Here, I will describe a method to learn phenotypes without requiring hand-labeled cells for training. Instead, a classifier is trained from negative and positive controls in the experiment, where the positives are known to be enriched in the phenotype of interest, even if only slightly (e.g., 55% vs. 45% penetrance). By nonlinearly projecting cells into a random feature space, we can use efficient linear methods but still benefit from nonlinear notions of similarity, and can overcome experimental noise by training on millions of cells. Using the resulting classifier to assign soft labels to each cell in the experiment, we can identify enriched samples ("hits") nonparametrically. Furthermore, we are developing techniques to automatically identify relevant cellular phenotypes in large-scale chemical profiling experiments.
关 键 词: 高通量实验; 细胞表型; 迭代检测; 非线性投影; 特征空间
课程来源: 视频讲座网
最后编审: 2020-05-29:吴雨秋(课程编辑志愿者)
阅读次数: 107