A fully automatic gridding method for cDNA microarray images

<p>Abstract</p> <p>Background</p> <p>Processing cDNA microarray images is a crucial step in gene expression analysis, since any errors in early stages affect subsequent steps, leading to possibly erroneous biological conclusions. When processing the underlying images, accurately separating the sub-grids and spots is extremely important for subsequent steps that include segmentation, quantification, normalization and clustering.</p> <p>Results</p> <p>We propose a parameterless and fully automatic approach that first detects the sub-grids given the entire microarray image, and then detects the locations of the spots in each sub-grid. The approach, first, detects and corrects rotations in the images by applying an affine transformation, followed by a polynomial-time optimal multi-level thresholding algorithm used to find the positions of the sub-grids in the image and the positions of the spots in each sub-grid. Additionally, a new validity index is proposed in order to find the correct number of sub-grids in the image, and the correct number of spots in each sub-grid. Moreover, a refinement procedure is used to correct possible misalignments and increase the accuracy of the method.</p> <p>Conclusions</p> <p>Extensive experiments on real-life microarray images and a comparison to other methods show that the proposed method performs these tasks fully automatically and with a very high degree of accuracy. Moreover, unlike previous methods, the proposed approach can be used in various type of microarray images with different resolutions and spot sizes and does not need any parameter to be adjusted.</p

Novel pattern recognition approaches for transcriptomics data analysis

We proposed a family of methods for transcriptomics and genomics data analysis based on multi-level thresholding approach, such as OMTG for sub-grid and spot detection in DNA microarrays, and OMT for detecting significant regions based on next generation sequencing data. Extensive experiments on real-life datasets and a comparison to other methods show that the proposed methods perform these tasks fully automatically and with a very high degree of accuracy. Moreover, unlike previous methods, the proposed approaches can be used in various types of transcriptome analysis problems such as microarray image gridding with different resolutions and spot sizes as well as finding the interacting regions of DNA with a protein of interest using ChIP-Seq data without any need for parameter adjustment. We also developed constrained multi-level thresholding (CMT), an algorithm used to detect enriched regions on ChIP-Seq data with the ability of targeting regions within a specific range. We show that CMT has higher accuracy in detecting enriched regions (peaks) by objectively assessing its performance relative to other previously proposed peak finders. This is shown by testing three algorithms on the well-known FoxA1 Data set, four transcription factors (with a total of six antibodies) for Drosophila melanogaster and the H3K4ac antibody dataset. Finally, we propose a tree-based approach that conducts gene selection and builds a classifier simultaneously, in order to select the minimal number of genes that would reliably predict a given breast cancer subtype. Our results support that this modified approach to gene selection yields a small subset of genes that can predict subtypes with greater than 95%overall accuracy. In addition to providing a valuable list of targets for diagnostic purposes, the gene ontologies of the selected genes suggest that these methods have isolated a number of potential genes involved in breast cancer biology, etiology and potentially novel therapeutics

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

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

An Overview of DNA Microarray Grid Alignment and Foreground Separation Approaches

This paper overviews DNA microarray grid alignment and foreground separation approaches. Microarray grid alignment and foreground separation are the basic processing steps of DNA microarray images that affect the quality of gene expression information, and hence impact our confidence in any data-derived biological conclusions. Thus, understanding microarray data processing steps becomes critical for performing optimal microarray data analysis. In the past, the grid alignment and foreground separation steps have not been covered extensively in the survey literature. We present several classifications of existing algorithms, and describe the fundamental principles of these algorithms. Challenges related to automation and reliability of processed image data are outlined at the end of this overview paper.</p

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

Bioinformatics framework for genotyping microarray data analysis

Functional genomics is a flourishing science enabled by recent technological breakthroughs in high-throughput instrumentation and microarray data analysis. Genotyping microarrays establish the genotypes of DNA sequences containing single nucleotide polymorphisms (SNPs), and can help biologists probe the functions of different genes and/or construct complex gene interaction networks. The enormous amount of data from these experiments makes it infeasible to perform manual processing to obtain accurate and reliable results in daily routines. Advanced algorithms as well as an integrated software toolkit are needed to help perform reliable and fast data analysis. The author developed a MatlabTM based software package, called TIMDA (a Toolkit for Integrated Genotyping Microarray Data Analysis), for fully automatic, accurate and reliable genotyping microarray data analysis. The author also developed new algorithms for image processing and genotype-calling. The modular design of TIMDA allows satisfactory extensibility and maintainability. TIMDA is open source (URL: http://timda.SF.net and can be easily customized by users to meet their particular needs. The quality and reproducibility of results in image processing and genotype-calling and the ease of customization indicate that TIMDA is a useful package for genomics research

ATMAD : robust image analysis for Automatic Tissue MicroArray De-arraying

International audienceBackground. Over the last two decades, an innovative technology called Tissue Microarray (TMA),which combines multi-tissue and DNA microarray concepts, has been widely used in the field ofhistology. It consists of a collection of several (up to 1000 or more) tissue samples that are assembledonto a single support – typically a glass slide – according to a design grid (array) layout, in order toallow multiplex analysis by treating numerous samples under identical and standardized conditions.However, during the TMA manufacturing process, the sample positions can be highly distorted fromthe design grid due to the imprecision when assembling tissue samples and the deformation of theembedding waxes. Consequently, these distortions may lead to severe errors of (histological) assayresults when the sample identities are mismatched between the design and its manufactured output.The development of a robust method for de-arraying TMA, which localizes and matches TMAsamples with their design grid, is therefore crucial to overcome the bottleneck of this prominenttechnology.Results. In this paper, we propose an Automatic, fast and robust TMA De-arraying (ATMAD)approach dedicated to images acquired with bright field and fluorescence microscopes (or scanners).First, tissue samples are localized in the large image by applying a locally adaptive thresholdingon the isotropic wavelet transform of the input TMA image. To reduce false detections, a parametricshape model is considered for segmenting ellipse-shaped objects at each detected position.Segmented objects that do not meet the size and the roundness criteria are discarded from thelist of tissue samples before being matched with the design grid. Sample matching is performed byestimating the TMA grid deformation under the thin-plate model. Finally, thanks to the estimateddeformation, the true tissue samples that were preliminary rejected in the early image processingstep are recognized by running a second segmentation step.Conclusions. We developed a novel de-arraying approach for TMA analysis. By combining waveletbaseddetection, active contour segmentation, and thin-plate spline interpolation, our approach isable to handle TMA images with high dynamic, poor signal-to-noise ratio, complex background andnon-linear deformation of TMA grid. In addition, the deformation estimation produces quantitativeinformation to asset the manufacturing quality of TMAs

Microarray image processing : a novel neural network framework

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.EThOS - Electronic Theses Online ServiceAleppo University, SyriaGBUnited Kingdo