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Register a new userStructured Correlation Detection with Application to Colocalization Analysis in Dual-Channel Fluorescence Microscopic Imaging
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Added by
Ming Yuan
Publication date
2016
fields
Mathematical Statistics
and research's language is
English
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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.
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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.
In Functional Data Analysis, data are commonly assumed to be smooth functions on a fixed interval of the real line. In this work, we introduce a comprehensive framework for the analysis of functional data, whose domain is a two-dimensional manifold and the domain itself is subject to variability from sample to sample. We formulate a statistical model for such data, here called Functions on Surfaces, which enables a joint representation of the geometric and functional aspects, and propose an associated estimation framework. We assess the validity of the framework by performing a simulation study and we finally apply it to the analysis of neuroimaging data of cortical thickness, acquired from the brains of different subjects, and thus lying on domains with different geometries.
Information geometry uses the formal tools of differential geometry to describe the space of probability distributions as a Riemannian manifold with an additional dual structure. The formal equivalence of compositional data with discrete probability distributions makes it possible to apply the same description to the sample space of Compositional Data Analysis (CoDA). The latter has been formally described as a Euclidean space with an orthonormal basis featuring components that are suitable combinations of the original parts. In contrast to the Euclidean metric, the information-geometric description singles out the Fisher information metric as the only one keeping the manifolds geometric structure invariant under equivalent representations of the underlying random variables. Well-known concepts that are valid in Euclidean coordinates, e.g., the Pythogorean theorem, are generalized by information geometry to corresponding notions that hold for more general coordinates. In briefly reviewing Euclidean CoDA and, in more detail, the information-geometric approach, we show how the latter justifies the use of distance measures and divergences that so far have received little attention in CoDA as they do not fit the Euclidean geometry favored by current thinking. We also show how entropy and relative entropy can describe amalgamations in a simple way, while Aitchison distance requires the use of geometric means to obtain more succinct relationships. We proceed to prove the information monotonicity property for Aitchison distance. We close with some thoughts about new directions in CoDA where the rich structure that is provided by information geometry could be exploited.
Cross-correlation signals are recorded from fluorescence photons scattered in free space off a trapped ion structure. The analysis of the signal allows for unambiguously revealing the spatial frequency, thus the distance, as well as the spatial alignment of the ions. For the case of two ions we obtain from the cross-correlations a spatial frequency $f_text{spatial}=1490 pm 2_{stat.}pm 8_{syst.},text{rad}^{-1}$, where the statistical uncertainty improves with the integrated number of correlation events as $N^{-0.51pm0.06}$. We independently determine the spatial frequency to be $1494pm 11,text{rad}^{-1}$, proving excellent agreement. Expanding our method to the case of three ions, we demonstrate its functionality for two-dimensional arrays of emitters of indistinguishable photons, serving as a model system to yield structural information where direct imaging techniques fail.
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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