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Register a new userAutomated and Robust Quantification of Colocalization in Dual-Color Fluorescence Microscopy: A Nonparametric Statistical Approach
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Colocalization is a powerful tool to study the interactions between fluorescently labeled molecules in biological fluorescence microscopy. However, existing techniques for colocalization analysis have not undergone continued development especially in regards to robust statistical support. In this paper, we examine two of the most popular quantification techniques for colocalization and argue that they could be improved upon using ideas from nonparametric statistics and scan statistics. In particular, we propose a new colocalization metric that is robust, easily implementable, and optimal in a rigorous statistical testing framework. Application to several benchmark datasets, as well as biological examples, further demonstrates the usefulness of the proposed technique.
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Colocalization analysis aims to study complex spatial associations between bio-molecules via optical imaging techniques. However, existing colocalization analysis workflows only assess an average degree of colocalization within a certain region of interest and ignore the unique and valuable spatial information offered by microscopy. In the current work, we introduce a new framework for colocalization analysis that allows us to quantify colocalization levels at each individual location and automatically identify pixels or regions where colocalization occurs. The framework, referred to as spatially adaptive colocalization analysis (SACA), integrates a pixel-wise local kernel model for colocalization quantification and a multi-scale adaptive propagation-separation strategy for utilizing spatial information to detect colocalization in a spatially adaptive fashion. Applications to simulated and real biological datasets demonstrate the practical merits of SACA in what we hope to be an easily applicable and robust colocalization analysis method. In addition, theoretical properties of SACA are investigated to provide rigorous statistical justification.
We study a methodology to tackle the NASA Langley Uncertainty Quantification Challenge problem, based on an integration of robust optimization, more specifically a recent line of research known as distributionally robust optimization, and importance sampling in Monte Carlo simulation. The main computation machinery in this integrated methodology boils down to solving sampled linear programs. We will illustrate both our numerical performances and theoretical statistical guarantees obtained via connections to nonparametric hypothesis testing.
CT imaging is crucial for diagnosis, assessment and staging COVID-19 infection. Follow-up scans every 3-5 days are often recommended for disease progression. It has been reported that bilateral and peripheral ground glass opacification (GGO) with or without consolidation are predominant CT findings in COVID-19 patients. However, due to lack of computerized quantification tools, only qualitative impression and rough description of infected areas are currently used in radiological reports. In this paper, a deep learning (DL)-based segmentation system is developed to automatically quantify infection regions of interest (ROIs) and their volumetric ratios w.r.t. the lung. The performance of the system was evaluated by comparing the automatically segmented infection regions with the manually-delineated ones on 300 chest CT scans of 300 COVID-19 patients. For fast manual delineation of training samples and possible manual intervention of automatic results, a human-in-the-loop (HITL) strategy has been adopted to assist radiologists for infection region segmentation, which dramatically reduced the total segmentation time to 4 minutes after 3 iterations of model updating. The average Dice simiarility coefficient showed 91.6% agreement between automatic and manual infaction segmentations, and the mean estimation error of percentage of infection (POI) was 0.3% for the whole lung. Finally, possible applications, including but not limited to analysis of follow-up CT scans and infection distributions in the lobes and segments correlated with clinical findings, were discussed.
Motivated by the problem of colocalization analysis in fluorescence microscopic imaging, we study in this paper structured detection of correlated regions between two random processes observed on a common domain. We argue that although intuitive, direct use of the maximum log-likelihood statistic suffers from potential bias and substantially reduced power, and introduce a simple size-based normalization to overcome this problem. We show that scanning with the proposed size-corrected likelihood ratio statistics leads to optimal correlation detection over a large collection of structured correlation detection problems.
Statistical inference in high dimensional settings has recently attracted enormous attention within the literature. However, most published work focuses on the parametric linear regression problem. This paper considers an important extension of this problem: statistical inference for high dimensional sparse nonparametric additive models. To be more precise, this paper develops a methodology for constructing a probability density function on the set of all candidate models. This methodology can also be applied to construct confidence intervals for various quantities of interest (such as noise variance) and confidence bands for the additive functions. This methodology is derived using a generalized fiducial inference framework. It is shown that results produced by the proposed methodology enjoy correct asymptotic frequentist properties. Empirical results obtained from numerical experimentation verify this theoretical claim. Lastly, the methodology is applied to a gene expression data set and discovers new findings for which most existing methods based on parametric linear modeling failed to observe.
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