Improvements on segment based contours method for DNA microarray image segmentation

DNA microarray is an efficient biotechnology tool for scientists to measure the expression levels of large numbers of genes, simultaneously. To obtain the gene expression, microarray image analysis needs to be conducted. Microarray image segmentation is a fundamental step in the microarray analysis process. Segmentation gives the intensities of each probe spot in the array image, and those intensities are used to calculate the gene expression in subsequent analysis procedures. Therefore, more accurate and efficient microarray image segmentation methods are being pursued all the time. In this dissertation, we are making efforts to obtain more accurate image segmentation results. We improve the Segment Based Contours (SBC) method by implementing a higher order of finite difference schemes in the partial differential equation used in our mathematical model. Therefore, we achieved two improved methods: the 4th order method and the 8th order method. The 4th order method could be applied to segment both the cDNA microarray images and the Affymetrix GeneChips, while the 8 th order method could be applied to segment only the cDNA microarray images, due to the limitation of the current image resolution. The mathematical derivation shows that both our 4th order method and 8th order method are better approximating the C-V model [Chan & Vese, 2001] than the SBC method, which means they will offer more accurate segmentation results than the SBC method. Besides mathematical proof, we do the practical experiments to double check the conclusion drawn from the mathematical derivation. Both the 4th order method and the 8th order method are used to segment microarray images, and the output segmentation results—the intensities of each probe cell in the microarray image—are being compared to the results from the SBC method and two other mainstream microarray image segmentation methods, the Globaly Optimal Geodesic Active Contours (GOGAC) method and the GeneChip Operating System (GCOS) software, for more valid evaluation. To give the ground true values of intensities as the standard for different segmentation methods comparison, a microarray image simulator is introduced to generate the simulated images used in our experiments. The simulated microarray images have all the characteristics that real microarray images have, and the true intensity values of each probe spot in the image are provided by this simulator. Intensity values segmented by those segmentation methods are compared to the true intensity values. Therefore, we could evaluate that one segmentation method is more accurate than the other methods if its intensity values are closer to the true values. We conduct several analysis procedures in the segmentation results comparison part to convince our analysis results. Intensity analysis, paired t-test and Unweighted Pair Group Method with Arithmetic Mean (UPGMA) hierarchy cluster experiments are applied to analyze intensity values of those methods. The segmentation output analysis results show that our 4th order method and the 8th order method could offer more accurate segmentation than the SBC method, the GCOS method and the GOGAC method on some kinds of the microarray images. There are accuracy improvements achieved with the 8 th order method over the 4th order method on the cDNA microarray image. On the Bovine type Affymetrix GeneChip image, there is no significant difference between the 4th order method and the 8th order method

Gene expression reliability estimation through cluster-based analysis

Gene expression is the fundamental control of the structure and functions of the cellular versatility and adaptability of any organisms. The measurement of gene expressions is performed on images generated by optical inspection of microarray devices which allow the simultaneous analysis of thousands of genes. The images produced by these devices are used to calculate the expression levels of mRNA in order to draw diagnostic information related to human disease. The quality measures are mandatory in genes classification and in the decision-making diagnostic. However, microarrays are characterized by imperfections due to sample contaminations, scratches, precipitation or imperfect gridding and spot detection. The automatic and efficient quality measurement of microarray is needed in order to discriminate faulty gene expression levels. In this paper we present a new method for estimate the quality degree and the data's reliability of a microarray analysis. The efficiency of the proposed approach in terms of genes expression classification has been demonstrated through a clustering supervised analysis performed on a set of three different histological samples related to the Lymphoma's cancer diseas

A multi-view approach to cDNA micro-array analysis

The official published version can be obtained from the link below.Microarray has emerged as a powerful technology that enables biologists to study thousands of genes simultaneously, therefore, to obtain a better understanding of the gene interaction and regulation mechanisms. This paper is concerned with improving the processes involved in the analysis of microarray image data. The main focus is to clarify an image's feature space in an unsupervised manner. In this paper, the Image Transformation Engine (ITE), combined with different filters, is investigated. The proposed methods are applied to a set of real-world cDNA images. The MatCNN toolbox is used during the segmentation process. Quantitative comparisons between different filters are carried out. It is shown that the CLD filter is the best one to be applied with the ITE.This work was supported in part by the Engineering and Physical Sciences Research Council (EPSRC) of the UK under Grant GR/S27658/01, the National Science Foundation of China under Innovative Grant 70621001, Chinese Academy of Sciences under Innovative Group Overseas Partnership Grant, the BHP Billiton Cooperation of Australia Grant, the International Science and Technology Cooperation Project of China under Grant 2009DFA32050 and the Alexander von Humboldt Foundation of Germany

A novel neural network approach to cDNA microarray image segmentation

This is the post-print version of the Article. The official published version can be accessed from the link below. Copyright @ 2013 Elsevier.Microarray technology has become a great source of information for biologists to understand the workings of DNA which is one of the most complex codes in nature. Microarray images typically contain several thousands of small spots, each of which represents a different gene in the experiment. One of the key steps in extracting information from a microarray image is the segmentation whose aim is to identify which pixels within an image represent which gene. This task is greatly complicated by noise within the image and a wide degree of variation in the values of the pixels belonging to a typical spot. In the past there have been many methods proposed for the segmentation of microarray image. In this paper, a new method utilizing a series of artificial neural networks, which are based on multi-layer perceptron (MLP) and Kohonen networks, is proposed. The proposed method is applied to a set of real-world cDNA images. Quantitative comparisons between the proposed method and commercial software GenePix(®) are carried out in terms of the peak signal-to-noise ratio (PSNR). This method is shown to not only deliver results comparable and even superior to existing techniques but also have a faster run time.This work was funded in part by the National Natural Science Foundation of China under Grants 61174136 and 61104041, the Natural Science Foundation of Jiangsu Province of China under Grant BK2011598, the International Science and Technology Cooperation Project of China under Grant No. 2011DFA12910, the Engineering and Physical Sciences Research Council (EPSRC) of the U.K. under Grant GR/S27658/01, the Royal Society of the U.K., and the Alexander von Humboldt Foundation of Germany

A biomimetic algorithm for the improved detection of microarray features,

One the major difficulties of microarray technology relate to the processing of large and - importantly - error-loaded images of the dots on the chip surface. Whatever the source of these errors, those obtained in the first stage of data acquisition - segmentation - are passed down to the subsequent processes, with deleterious results. As it has been demonstrated recently that biological systems have evolved algorithms that are mathematically efficient, this contribution attempts to test an algorithm that mimics a bacterial-"patented" algorithm for the search of available space and nutrients to find, "zero-in" and eventually delimitate the features existent on the microarray surface

Cellular neural networks, Navier-Stokes equation and microarray image reconstruction

Copyright @ 2011 IEEE.Although the last decade has witnessed a great deal of improvements achieved for the microarray technology, many major developments in all the main stages of this technology, including image processing, are still needed. Some hardware implementations of microarray image processing have been proposed in the literature and proved to be promising alternatives to the currently available software systems. However, the main drawback of those proposed approaches is the unsuitable addressing of the quantification of the gene spot in a realistic way without any assumption about the image surface. Our aim in this paper is to present a new image-reconstruction algorithm using the cellular neural network that solves the Navier–Stokes equation. This algorithm offers a robust method for estimating the background signal within the gene-spot region. The MATCNN toolbox for Matlab is used to test the proposed method. Quantitative comparisons are carried out, i.e., in terms of objective criteria, between our approach and some other available methods. It is shown that the proposed algorithm gives highly accurate and realistic measurements in a fully automated manner within a remarkably efficient time

Segmentation and intensity estimation for microarray images with saturated pixels

<p>Abstract</p> <p>Background</p> <p>Microarray image analysis processes scanned digital images of hybridized arrays to produce the input spot-level data for downstream analysis, so it can have a potentially large impact on those and subsequent analysis. Signal saturation is an optical effect that occurs when some pixel values for highly expressed genes or peptides exceed the upper detection threshold of the scanner software (2¹⁶- 1 = 65, 535 for 16-bit images). In practice, spots with a sizable number of saturated pixels are often flagged and discarded. Alternatively, the saturated values are used without adjustments for estimating spot intensities. The resulting expression data tend to be biased downwards and can distort high-level analysis that relies on these data. Hence, it is crucial to effectively correct for signal saturation.</p> <p>Results</p> <p>We developed a flexible mixture model-based segmentation and spot intensity estimation procedure that accounts for saturated pixels by incorporating a censored component in the mixture model. As demonstrated with biological data and simulation, our method extends the dynamic range of expression data beyond the saturation threshold and is effective in correcting saturation-induced bias when the lost information is not tremendous. We further illustrate the impact of image processing on downstream classification, showing that the proposed method can increase diagnostic accuracy using data from a lymphoma cancer diagnosis study.</p> <p>Conclusions</p> <p>The presented method adjusts for signal saturation at the segmentation stage that identifies a pixel as part of the foreground, background or other. The cluster membership of a pixel can be altered versus treating saturated values as truly observed. Thus, the resulting spot intensity estimates may be more accurate than those obtained from existing methods that correct for saturation based on already segmented data. As a model-based segmentation method, our procedure is able to identify inner holes, fuzzy edges and blank spots that are common in microarray images. The approach is independent of microarray platform and applicable to both single- and dual-channel microarrays.</p

Joint co-clustering: co-clustering of genomic and clinical bioimaging data

AbstractFor better understanding the genetic mechanisms underlying clinical observations, and better defining a group of potential candidates for protein-family-inhibiting therapy, it is interesting to determine the correlations between genomic, clinical data and data coming from high resolution and fluorescent microscopy. We introduce a computational method, called joint co-clustering, that can find co-clusters or groups of genes, bioimaging parameters and clinical traits that are believed to be closely related to each other based on the given empirical information. As bioimaging parameters, we quantify the expression of growth factor receptor EGFR/erb-B family in non-small cell lung carcinoma (NSCLC) through a fully-automated computer-aided analysis approach. This immunohistochemical analysis is usually performed by pathologists via visual inspection of tissue samples images. Our fully-automated techniques streamlines this error-prone and time-consuming process, thereby facilitating analysis and diagnosis. Experimental results for several real-life datasets demonstrate the high quantitative precision of our approach. The joint co-clustering method was tested with the receptor EGFR/erb-B family data on non-small cell lung carcinoma (NSCLC) tissue and identified statistically significant co-clusters of genes, receptor protein expression and clinical traits. The validation of our results with the literature suggest that the proposed method can provide biologically meaningful co-clusters of genes and traits and that it is a very promising approach to analyse large-scale biological data and to study multi-factorial genetic pathologies through their genetic alterations