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

Microarray sub-grid detection: A novel algorithm

This is the post print version of the article. The official published version can be obtained from the link below - Copyright 2007 Taylor & Francis LtdA novel algorithm for detecting microarray subgrids is proposed. The only input to the algorithm is the raw microarray image, which can be of any resolution, and the subgrid detection is performed with no prior assumptions. The algorithm consists of a series of methods of spot shape detection, spot filtering, spot spacing estimation, and subgrid shape detection. It is shown to be able to divide images of varying quality into subgrid regions with no manual interaction. The algorithm is robust against high levels of noise and high percentages of poorly expressed or missing spots. In addition, it is proved to be effective in locating regular groupings of primitives in a set of non-microarray images, suggesting potential application in the general area of image processing

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

GridWeaver: A Fully-Automatic System for Microarray Image Analysis Using Fast Fourier Transforms

Experiments using microarray technology generate large amounts of image data that are used in the analysis of genetic function. An important stage in the analysis is the determination of relative intensities of spots on the images generated. This paper presents GridWeaver, a program that reads in images from a microarray experiment, automatically locates subgrids and spots in the images, and then determines the spot intensities needed in the analysis of gene function. Automatic gridding is performed by running Fast Fourier Transforms on pixel intensity sums. Tests on several data sets show that the program responds well even on images that have significant noise, both random and systemic

Fully automatic classification of breast cancer microarray images

AbstractA microarray image is used as an accurate method for diagnosis of cancerous diseases. The aim of this research is to provide an approach for detection of breast cancer type. First, raw data is extracted from microarray images. Determining the exact location of each gene is carried out using image processing techniques. Then, by the sum of the pixels associated with each gene, the amount of “genes expression” is extracted as raw data. To identify more effective genes, information gain method on the set of raw data is used. Finally, the type of cancer can be recognized via analyzing the obtained data using a decision tree. The proposed approach has an accuracy of 95.23% in diagnosing the breast cancer types

A TMA De-Arraying Method for High Throughput Biomarker Discovery in Tissue Research

BACKGROUND: Tissue MicroArrays (TMAs) represent a potential high-throughput platform for the analysis and discovery of tissue biomarkers. As TMA slides are produced manually and subject to processing and sectioning artefacts, the layout of TMA cores on the final slide and subsequent digital scan (TMA digital slide) is often disturbed making it difficult to associate cores with their original position in the planned TMA map. Additionally, the individual cores can be greatly altered and contain numerous irregularities such as missing cores, grid rotation and stretching. These factors demand the development of a robust method for de-arraying TMAs which identifies each TMA core, and assigns them to their appropriate coordinates on the constructed TMA slide. METHODOLOGY: This study presents a robust TMA de-arraying method consisting of three functional phases: TMA core segmentation, gridding and mapping. The segmentation of TMA cores uses a set of morphological operations to identify each TMA core. Gridding then utilises a Delaunay Triangulation based method to find the row and column indices of each TMA core. Finally, mapping correlates each TMA core from a high resolution TMA whole slide image with its name within a TMAMap. CONCLUSION: This study describes a genuine robust TMA de-arraying algorithm for the rapid identification of TMA cores from digital slides. The result of this de-arraying algorithm allows the easy partition of each TMA core for further processing. Based on a test group of 19 TMA slides (3129 cores), 99.84% of cores were segmented successfully, 99.81% of cores were gridded correctly and 99.96% of cores were mapped with their correct names via TMAMaps. The gridding of TMA cores were also extensively tested using a set of 113 pseudo slide (13,536 cores) with a variety of irregular grid layouts including missing cores, rotation and stretching. 100% of the cores were gridded correctly

AUTOMATIC GRIDDING CITRA MICROARRAY DENGAN MENGGUNAKAN IMAGE THRESHOLDING

.Citra microarray adalah citra hasil pemindaian laser scanner terhadap microarray yang umumnya digunakan untuk mendeteksi perbedaan efek hibridisasi dari dua kelompok sampel DNA. Citra tersebut kemudian dianalisis untuk mendapatkan intensitas fluorescence setiap titik mikroskopis DNA pada microarray. Salah satu tahapan analisis citra microarray adalah menentukan daerah pada citra microarray yang memuat satu titik mikroskopis DNA. Penentuan daerah ini dapat dilakukan secara manual maupun secara otomatis atau yang dikenal dengan automatic gridding. Beberapa penelitian menggunakan k-mean clustering untuk melakukan automatic gridding, tetapi metode ini membutuhkan waktu komputasi yang cukup lama. Dalam makalah ini akan dipaparkan metode untuk automatic gridding dengan menggunakan image thresholding. Selain itu juga dilakukan simulasi dengan menggunakan MATLAB untuk membandingkan waktu yang diperlukan untuk komputasi automatic gridding dengan image thresholding dan automatic gridding dengan k-mean clustering. Hasil simulasi menunjukkan bahwa waktu komputasi automatic gridding dengan image thresholding jauh lebih sedikit di bandingkan dengan automatic gridding dengan k-mean clustering

Microarray image processing: A novel neural network framework

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.Due to the vast success of bioengineering techniques, a series of large-scale analysis tools has been developed to discover the functional organization of cells. Among them, cDNA microarray has emerged as a powerful technology that enables biologists to cDNA microarray technology has enabled biologists to study thousands of genes simultaneously within an entire organism, and thus obtain a better understanding of the gene interaction and regulation mechanisms involved. Although microarray technology has been developed so as to offer high tolerances, there exists high signal irregularity through the surface of the microarray image. The imperfection in the microarray image generation process causes noises of many types, which contaminate the resulting image. These errors and noises will propagate down through, and can significantly affect, all subsequent processing and analysis. Therefore, to realize the potential of such technology it is crucial to obtain high quality image data that would indeed reflect the underlying biology in the samples. One of the key steps in extracting information from a microarray image is segmentation: identifying which pixels within an image represent which gene. This area of spotted microarray image analysis has received relatively little attention relative to the advances in proceeding analysis stages. But, the lack of advanced image analysis, including the segmentation, results in sub-optimal data being used in all downstream analysis methods. Although there is recently much research on microarray image analysis with many methods have been proposed, some methods produce better results than others. In general, the most effective approaches require considerable run time (processing) power to process an entire image. Furthermore, there has been little progress on developing sufficiently fast yet efficient and effective algorithms the segmentation of the microarray image by using a highly sophisticated framework such as Cellular Neural Networks (CNNs). It is, therefore, the aim of this thesis to investigate and develop novel methods processing microarray images. The goal is to produce results that outperform the currently available approaches in terms of PSNR, k-means and ICC measurements.Aleppo University, Syri

Copasetic analysis: Automated analysis of biological gene expression images

Copyright [2004] IEEE. This material is posted here with permission of the IEEE. Such permission of the IEEE does not in any way imply IEEE endorsement of any of Brunel University's products or services. Internal or personal use of this material is permitted. However, permission to reprint/republish this material for advertising or promotional purposes or for creating new collective works for resale or redistribution must be obtained from the IEEE by writing to [email protected]. By choosing to view this document, you agree to all provisions of the copyright laws protecting it.In the past decade computational biology has come to the forefront of the public's perception with advancements in domain knowledge and a variety of analysis techniques. With the recent completion of projects like the human genome sequence, and the development of microarray chips it has become possible to simultaneously analyse expression levels for thousands of genes. Typically, a slide surface of less than 24 cm2, receptors for 30,000 genes can be printed, but currently the analysis process is a time consuming semi-autonomous step requiring human guidance. The paper proposes a framework, which facilitates automated processing of these images. This is supported by real world examples, which demonstrate the technique's capabilities along with results, which show a marked improvement over existing implementations