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

Paradigm of tunable clustering using binarization of consensus partition matrices (Bi-CoPaM) for gene discovery

Copyright @ 2013 Abu-Jamous et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Clustering analysis has a growing role in the study of co-expressed genes for gene discovery. Conventional binary and fuzzy clustering do not embrace the biological reality that some genes may be irrelevant for a problem and not be assigned to a cluster, while other genes may participate in several biological functions and should simultaneously belong to multiple clusters. Also, these algorithms cannot generate tight clusters that focus on their cores or wide clusters that overlap and contain all possibly relevant genes. In this paper, a new clustering paradigm is proposed. In this paradigm, all three eventualities of a gene being exclusively assigned to a single cluster, being assigned to multiple clusters, and being not assigned to any cluster are possible. These possibilities are realised through the primary novelty of the introduction of tunable binarization techniques. Results from multiple clustering experiments are aggregated to generate one fuzzy consensus partition matrix (CoPaM), which is then binarized to obtain the final binary partitions. This is referred to as Binarization of Consensus Partition Matrices (Bi-CoPaM). The method has been tested with a set of synthetic datasets and a set of five real yeast cell-cycle datasets. The results demonstrate its validity in generating relevant tight, wide, and complementary clusters that can meet requirements of different gene discovery studies.National Institute for Health Researc

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

Microarray spot partitioning by autonoumsly organising maps thorugh contour model

In cDNA microarray image analysis, classification of pixels as forefront area and the area covered by background is very challenging. In microarray experimentation, identifying forefront area of desired spots is nothing but computation of forefront pixels concentration, area covered by spot and shape of the spots. In this piece of writing, an innovative way for spot partitioning of microarray images using autonomously organizing maps (AOM) method through C-V model has been proposed. Concept of neural networks has been incorpated to train and to test microarray spots.In a trained AOM the comprehensive information arising from the prototypes of created neurons are clearly integrated to decide whether to get smaller or get bigger of contour. During the process of optimization, this is done in an iterative manner. Next using C-V model, inside curve area of trained spot is compared with test spot finally curve fitting is done.The presented model can handle spots with variations in terms of shape and quality of the spots and meanwhile it is robust to the noise. From the review of experimental work, presented approach is accurate over the approaches like C-means by fuzzy, Morphology sectionalization

Classification of Acute Leukemia using Fuzzy Neural Networks

Accurate classification of cancers based on microarray gene expressions is very important for doctors to choose a proper treatment. In this paper, we compared ten filter based gene selection methods in order to differentiate acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) in leukemia dataset. Dimensionality reduction methods, such as Spearman Correlation Coefficient and Wilcoxon Rank Sum Statistics are used for gene selection. The experimental results showed that the proposed gene selection methods are efficient, effective, and robust in identifying differentially expressed genes. Adopting the existing SVM-based and KNN-based classifiers, the selected genes by filter based methods in general give more accurate classification results, typically when the sample class sizes in the training dataset are unbalanced

Automatic gridding of DNA microarray images.

Microarray (DNA chip) technology is having a significant impact on genomic studies. Many fields, including drug discovery and toxicological research, will certainly benefit from the use of DNA microarray technology. Microarray analysis is replacing traditional biological assays based on gels, filters and purification columns with small glass chips containing tens of thousands of DNA and protein sequences in agricultural and medical sciences. Microarray functions like biological microprocessors, enabling the rapid and quantitative analysis of gene expression patterns, patient genotypes, drug mechanisms and disease onset and progression on a genomic scale. Image analysis and statistical analysis are two important aspects of microarray technology. Gridding is necessary to accurately identify the location of each of the spots while extracting spot intensities from the microarray images and automating this procedure permits high-throughput analysis. Due to the deficiencies of the equipment that is used to print the arrays, rotations, misalignments, high contaminations with noise and artifacts, solving the grid segmentation problem in an automatic system is not trivial. The existing techniques to solve the automatic grid segmentation problem cover only limited aspect of this challenging problem and requires the user to specify or make assumptions about the spotsize, rows and columns in the grid and boundary conditions. An automatic gridding and spot quantification technique is proposed, which takes a matrix of pixels or a microarray image as input and makes no assumptions about the spotsize, rows and columns in the grid and is found to effective on datasets from GEO, Stanford genomic laboratories and on images obtained from private repositories. Paper copy at Leddy Library: Theses & Major Papers - Basement, West Bldg. / Call Number: Thesis2004 .V53. Source: Masters Abstracts International, Volume: 43-03, page: 0891. Adviser: Luis Rueda. Thesis (M.Sc.)--University of Windsor (Canada), 2004

Memory Acquisition and Retrieval Impact Different Epigenetic Processes that Regulate Gene Expression

Background: A fundamental question in neuroscience is how memories are stored and retrieved in the brain. Long-term memory formation requires transcription, translation and epigenetic processes that control gene expression. Thus, characterizing genome-wide the transcriptional changes that occur after memory acquisition and retrieval is of broad interest and importance. Genome-wide technologies are commonly used to interrogate transcriptional changes in discovery-based approaches. Their ability to increase scientific insight beyond traditional candidate gene approaches, however, is usually hindered by batch effects and other sources of unwanted variation, which are particularly hard to control in the study of brain and behavior. Results: We examined genome-wide gene expression after contextual conditioning in the mouse hippocampus, a brain region essential for learning and memory, at all the time-points in which inhibiting transcription has been shown to impair memory formation. We show that most of the variance in gene expression is not due to conditioning and that by removing unwanted variance through additional normalization we are able provide novel biological insights. In particular, we show that genes downregulated by memory acquisition and retrieval impact different functions: chromatin assembly and RNA processing, respectively. Levels of histone 2A variant H2AB are reduced only following acquisition, a finding we confirmed using quantitative proteomics. On the other hand, splicing factor Rbfox1 and NMDA receptor-dependent microRNA miR-219 are only downregulated after retrieval, accompanied by an increase in protein levels of miR-219 target CAMKIIγ. Conclusions: We provide a thorough characterization of coding and non-coding gene expression during long-term memory formation. We demonstrate that unwanted variance dominates the signal in transcriptional studies of learning and memory and introduce the removal of unwanted variance through normalization as a necessary step for the analysis of genome-wide transcriptional studies in the context of brain and behavior. We show for the first time that histone variants are downregulated after memory acquisition, and splicing factors and microRNAs after memory retrieval. Our results provide mechanistic insights into the molecular basis of cognition by highlighting the differential involvement of epigenetic mechanisms, such as histone variants and post-transcriptional RNA regulation, after acquisition and retrieval of memory