Circadian timing of anticancer medications has improved treatment tolerability and efficacy several fold, yet with intersubject variability. Using three C57BL/6-based mouse strains of both sexes, we identified three chronotoxicity classes with distinct circadian toxicity patterns of irinotecan, a topoisomerase I inhibitor active against colorectal cancer. Liver and colon circadian 24-hour expression patterns of clock genes Rev-erba and Bmal1 best discriminated these chronotoxicity classes, among 27 transcriptional 24-hour time series, according to sparse linear discriminant analysis. An 8-hour phase advance was found both for Rev-erba and Bmal1 mRNA expressions and for irinotecan chronotoxicity in clock-altered Per2 m/m mice. The application of a maximum-aposteriori Bayesian inference method identified a linear model based on Rev-erba and Bmal1 circadian expressions that accurately predicted for optimal irinotecan timing. The assessment of the Rev-erba and Bmal1 regulatory transcription loop in the molecular clock could critically improve the tolerability of chemotherapy through a mathematical model-based determination of host-specific optimal timing. Cancer Res; 73(24); 7176-88. Ó2013 AACR.
Bayesian approach has become a commonly used method for inverse problems arising in signal and image processing. One of the main advantages of the Bayesian approach is the possibility to propose unsupervised methods where the likelihood and prior model parameters can be estimated jointly with the main unknowns. In this paper, we propose to consider linear inverse problems in which the noise may be non-stationary and where we are looking for a sparse solution. To consider both of these requirements, we propose to use Student-t prior model both for the noise of the forward model and the unknown signal or image. The main interest of the Student-t prior model is its Infinite Gaussian Scale Mixture (IGSM) property. Using the resulted hierarchical prior models we obtain a joint posterior probability distribution of the unknowns of interest (input signal or image) and their associated hidden variables. To be able to propose practical methods, we use either a Joint Maximum A Posteriori (JMAP) estimator or an appropriate Variational Bayesian Approximation (VBA) technique to compute the Posterior Mean (PM) values. The proposed method is applied in many inverse problems such as deconvolution, image restoration and computed tomography. In this paper, we show only some results in signal deconvolution and in periodic components determination of some biological signals related to dynamic circadian clock period determination for cancer studies.
In order to improve the quality of X-ray Computed Tomography (CT) reconstruction for Non Destructive Testing (NDT), we propose a hierarchical prior modeling with a Bayesian approach. In this paper we present a new hierarchical structure for the inverse problem of CT by using a multivariate Studentt prior which enforces sparsity and preserves edges. This model can be adapted to the piecewise continuous image reconstruction problems. We demonstrate the feasibility of this method by comparing with some other state of the art methods. In this paper, we show simulation results in 2D where the image is the middle slice of the Shepp-Logan object but the algorithms are adapted to the big data size problem, which is one of the principal difficulties in the 3D CT reconstruction problem.
The toxicity and efficacy of more than 30 anticancer agents present very high variations, depending on the dosing time. Therefore, the biologists studying the circadian rhythm require a very precise method for estimating the periodic component (PC) vector of chronobiological signals. Moreover, in recent developments, not only the dominant period or the PC vector present a crucial interest but also their stability or variability. In cancer treatment experiments, the recorded signals corresponding to different phases of treatment are short, from 7 days for the synchronization segment to 2 or 3 days for the after-treatment segment. When studying the stability of the dominant period, we have to consider very short length signals relative to the prior knowledge of the dominant period, placed in the circadian domain. The classical approaches, based on Fourier transform (FT) methods are inefficient (i.e., lack of precision) considering the particularities of the data (i.e., the short length). Another particularity of the signals considered in such experiments is the level of noise: such signals are very noisy and establishing the periodic components that are associated with the biological phenomena and distinguishing them from the ones associated with the noise are difficult tasks. In this paper, we propose a new method for the estimation of the PC vector of biomedical signals, using the biological prior informations and considering a model that accounts for the noise. The experiments developed in cancer treatment context are recording signals expressing a limited number of periods. This is a prior information that can be translated as the sparsity of the PC vector. The proposed method considers the PC vector estimation as an Inverse Problem (IP) using the general Bayesian inference in order to infer the unknown of our model, i.e. the PC vector but also the hyperparameters (i.e the variances). The sparsity prior information is modeled using a sparsity enforcing prior law. In this paper, we propose a Student’s t distribution, viewed as the marginal distribution of a bivariate normal-inverse gamma distribution. We build a general infinite Gaussian scale mixture (IGSM) hierarchical model where we assign prior distributions also for the hyperparameters. The expression of the joint posterior law of the unknown PC vector and hyperparameters is obtained via Bayes rule, and then, the unknowns are estimated via joint maximum a posteriori (JMAP) or posterior mean (PM). For the PM estimator, the expression of the posterior distribution is approximated by a separable one, via variational Bayesian approximation (VBA), using the Kullback-Leibler (KL) divergence. For the PM estimation, two possibilities are considered: an approximation with a partially separable distribution and an approximation with a fully separable one. Both resulting algorithms corresponding to the PM estimation and the one corresponding to the JMAP estimation are iterative algorithms. The algorithms are presented in detail and are compared with the ones correspon...
Performance comparison of Bayesian iterative algorithms for three classes of sparsity enforcing priors with application in computed tomography. ABSTRACTThe piecewise constant or homogeneous image reconstruction in the context of X-ray Computed Tomography is considered within a Bayesian approach. More precisely, the sparse transformation of such images is modelled with heavy tailed distributions expressed as Normal variance mixtures marginals. The derived iterative algorithms (via Joint Maximum A Posteriori) have identical updating expressions, except for the estimated variances. We show that the behaviour of the each algorithm is different in terms of sensibility to the model selection and reconstruction performances when applied in Computed Tomography.
The recent developments in chronobiology need a periodic components variation analysis for the signals expressing the biological rhythms. A precise estimation of the periodic components vector is required. The classical approaches, based on FFT methods, are inefficient considering the particularities of the data (short length). In this paper we propose a new method, using the sparsity prior information (reduced number of non-zero values components). The considered law is the Student-t distribution, viewed as a marginal distribution of a Infinite Gaussian Scale Mixture (IGSM) defined via a hidden variable representing the inverse variances and modelled as a Gamma Distribution. The hyperparameters are modelled using the conjugate priors, i.e. using Inverse Gamma Distributions. The expression of the joint posterior law of the unknown periodic components vector, hidden variables and hyperparameters is obtained and then the unknowns are estimated via Joint Maximum A Posteriori (JMAP) and Posterior Mean (PM). For the PM estimator, the expression of the posterior law is approximated by a separable one, via the Bayesian Variational Approximation (BVA), using the Kullback-Leibler (KL) divergence. Finally we show the results on synthetic data in cancer treatment applications.
In this paper, a hierarchical prior model based on the Haar transformation and an appropriate Bayesian computational method for X-ray CT reconstruction are presented. Given the piece-wise continuous property of the object, a multilevel Haar transformation is used to associate a sparse representation for the object. The sparse structure is enforced via a generalized Student-t distribution (S t g ), expressed as the marginal of a normal-inverse Gamma distribution. The proposed model and corresponding algorithm are designed to adapt to specific 3D data sizes and to be used in both medical and industrial Non-Destructive Testing (NDT) applications. In the proposed Bayesian method, a hierarchical structured prior model is proposed, and the parameters are iteratively estimated. The initialization of the iterative algorithm uses the parameters of the prior distributions. A novel strategy for the initialization is presented and proven experimentally. We compare the proposed method with two state-of-the-art approaches, showing that our method has better reconstruction performance when fewer projections are considered and when projections are acquired from limited angles.
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