Collaborative Research: Image-based Readouts of Cellular State using Universal Morphology Embeddings

在显微镜下观察细胞，可以发现关于细胞过程的大量信息。例如，细胞的图像可以揭示细胞类型，以及细胞是健康的还是病态的等等。本研究旨在开发先进的计算模型来测量显微镜图像中的细胞特征。从图像中提取的细胞测量对于进行生物学研究非常有用，例如了解疾病的工作原理，诊断患者以及寻找有效的治疗方法。所有这些应用都是推进和促进国民健康的基础。这个项目的一个重要方面是，用于测量细胞特征的计算模型将是通用的，并且在许多获得显微镜图像的生物应用中可重复使用，而很少或不需要手动配置。这项研究将设计、开发并公开提供模型和自动化工具，以促进基础生物学研究和其他生物技术系统中基于图像的快速细胞分析。该项目将涉及不同的研究人员在一个包容的环境中工作，在尖端机器学习技术和细胞生物学图像分析的交叉点。不同的研究生和博士后将在一个包容的环境中接受尖端深度学习技术和细胞生物学图像分析交叉的培训。从图像中提取细胞形态特征是一个复杂的、特别的过程，没有很好的标准。通常，由于成像技术和实验目标的复杂性和多样性，成像项目从零开始开发定制方法，仅测量少量细胞特征。缺乏一种共同的方法来定义和测量单细胞的形态状态，这阻碍了研究人员实现成像的全部潜力，以推进细胞生物学。该项目旨在创建一个通用的深度学习模型，用于收集单细胞形态数据。它将很容易量化细胞形态在任何显微镜图像，几乎不需要训练。本研究的具体目标是：1)发展从各种成像实验中学习和提取细胞形态多维表示的方法；2)制定纠正批效应和消除技术变异的策略；3)制定分析和解释形态学特征的生物学意义的策略。对于学习表征，可以自适应处理多通道显微镜图像的神经网络将被开发和使用自监督学习进行训练。域自适应技术将扩展到校正批处理效果。重要的是，学习到的特征将被用于绘制细胞种群之间的关系，可解释的方法将被设计来促进它们的解释。本研究将准备来自各种公共来源的成像数据集，用于培训和评估，包括广泛生物图像基准集（BBBC）、图像数据资源（IDR）和人类蛋白质图谱（HPA）。本项目创建的模型将适用于大多数显微镜成像协议，将单细胞图像转换为生物学研究的定量数据。所有的结果、软件工具和模型都将在http://broad.io/morphemThis上公开，这反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

Observing cells under the microscope reveals an incredible amount of information about cellular processes. For example, images of cells can reveal cell types, and whether the cells are healthy or sick, among others. This research aims to develop advanced computational models to measure cellular traits in microscopy images. Cellular measurements taken from images are useful to conduct biological research such as understanding how diseases work, diagnosing patients, and searching for effective cures. All of these applications are fundamental to advance and promote national health. An important aspect of this project is that the computational models for measuring cellular traits will be of general purpose and reusable across many biological applications where microscopy images are acquired, with minimal or no manual configuration. This research will design, develop and make publicly available the models and automated tools to facilitate rapid image-based cellular analysis in basic biological research and other biotechnology systems. This project will involve diverse researchers working in an inclusive environment at the intersection of cutting-edge machine learning technologies and image analysis for cell biology. Diverse graduate students and postdocs will be trained in an inclusive environment at the intersection of cutting-edge deep learning technologies andimage analysis for cell biology.Extracting cell morphological features from images is a complex, ad-hoc process without well established standards. Typically, imaging projects develop custom approaches from scratch and measure only a few cellular features given the complexity and diversity of imaging techniques and experimental goals. This lack of a common methodology to define and measure the morphological state of single cells prevents researchers from realizing the full potential of imaging for advancing cell biology. This project aims to create a universal deep-learning model for collecting single-cell morphological data. It will readily quantify cell morphology in any microscopy image, requiring little to no training. The specific goals of this research are: 1) develop methods for learning and extracting multidimensional representations of cell morphology from diverse imaging experiments, 2) formulate strategies for correcting batch effects and removing technical variation, and 3) develop strategies for analyzing and interpreting the biological significance of morphological features. For learning representations, neural networks that can adaptively process multi-channel microscopy images will be developed and trained using self-supervised learning. Domain adaptation techniques will be extended for correcting batch effects. Importantly, learned features will be used to map relations between populations of cells and explainable methods will be designed to facilitate their interpretation. This research will prepare imaging datasets from various public sources for training and evaluation, including the Broad Bioimage Benchmark Collections (BBBC), the Image Data Resource (IDR), and the Human Protein Atlas (HPA). The models created in this project will be applicable to most microscopy imaging protocols to transform images of single cells into quantitative data for biological research. All the results, software tools and models will be publicly available at http://broad.io/morphemThis award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.