DNA Microarray Technology and Data Analysis in Cancer Research

We investigate discrete structures and combinatoric modeling of weighted prefix trees for managing and analyzing DNA microarray data. We describe the algorithms to construct the weighted trees for these data. Using these weighted trees with our algorithms, we propose methods to compute the appearance probability of a DNA microarray, to compare the informational distances in the expression of genes between the DNA microarrays, to search the characteristic microarrays and the group of candidate genes suggestive of a pathology.

In a number of domains, such as DNA microarray data analysis, we need to cluster simultaneously rows (genes) and columns (conditions) of a data matrix to identify groups of constant rows with a group of columns. This kind of clustering is called biclustering. Biclustering algorithms are extensively used in DNA microarray data analysis. More effective biclustering algorithms are highly desirable and needed. We introduce a new algorithm called BestBinBicluster for biclustering of binary microarray data. Our biclustering algorithm BestBinBicluster extracts a group of biclusters from binary matrix Mb. This algorithm adopts the strategy of one bicluster at a time. It is a novel alternative to extract biclusters from binary data sets. Our algorithm is based on the use of a polynomial function to search Greatest Common Divisor (GCD) and the use of Galois Lattice. We propose to generate the Enumerative BinBicluster Lattice. The performance of the proposed algorithm is assessed using both synthetic and real DNA microarray data; our algorithm outperforms other biclustering algorithms for binary microarray data. We test the biological significance using a gene annotation web tool to show that our proposed method is able to produce biologically relevant biclusters.

Clustering is an important approach to the analysis of DNA microarray data. In this paper, we develop a new algorithm that can cluster DNA microarray data with a graph cut based algorithm. The algorithm can generate a list of clustering results with statistically significant likelihood. It can thus resolve the issue where a gene product may participate in different subsets of co-expressed genes. Our testing results on two biological sets showed that this approach can achieve improved clustering accuracy, compared with other clustering methods.

We describe the use of a higher-order singular value decomposition (HOSVD) in transforming a data tensor of genes x "x-settings," that is, different settings of the experimental variable x x "y-settings," which tabulates DNA microarray data from different studies, to a "core tensor" of "eigenarrays" x "x-eigengenes" x "y-eigengenes." Reformulating this multilinear HOSVD such that it decomposes the data tensor into a linear superposition of all outer products of an eigenarray, an x- and a y-eigengene, that is, rank-1 "subtensors," we define the significance of each subtensor in terms of the fraction of the overall information in the data tensor that it captures. We illustrate this HOSVD with an integration of genome-scale mRNA expression data from three yeast cell cycle time courses, two of which are under exposure to either hydrogen peroxide or menadione. We find that significant subtensors represent independent biological programs or experimental phenomena. The picture that emerges suggests that the conserved genes YKU70, MRE11, AIF1, and ZWF1, and the processes of retrotransposition, apoptosis, and the oxidative pentose phosphate pathway that these genes are involved in, may play significant, yet previously unrecognized, roles in the differential effects of hydrogen peroxide and menadione on cell cycle progression. A genome-scale correlation between DNA replication initiation and RNA transcription, which is equivalent to a recently discovered correlation and might be due to a previously unknown mechanism of regulation, is independently uncovered.

RSCTC'2010 Discovery Challenge was a special event of Rough Sets and Current Trends in Computing conference. The challenge was organized in the form of an interactive on-line competition, at TUNEDIT.org platform, in days between Dec 1, 2009 and Feb 28, 2010. The task was related to feature selection in analysis of DNA microarray data and classification of samples for the purpose of medical diagnosis or treatment. Prizes were awarded to the best solutions. This paper describes organization of the competition and the winning solutions.

A finite mixture model is considered in which the mixing probabilities vary from observation to observation. Estimation of mixture components distributions, functional moments and densities is discussed. Tests are proposed for testing hypotheses on the moments. An application to the analysis of DNA microarray data is considered.

SummaryTo review the current state of the art in computational methods for the analysis of DNA microarray data.The review considers methods of microarray data collection, transformation and representation, comparisons and predictions of gene expression from the data, their mechanistic analysis, related systems biology, and the application of clustering techniques.Functional genomics approaches have greatly increased the rate at which data on biological systems is generated, leading to corresponding challenges in analyzing the data through advanced computational techniques . The paper compares and contrasts the application of computational clustering for discovery, comparison, and prediction of gene expression classes, together with their evaluation and relation to mechanistic analyses of biological systems.Methods for assaying gene expression levels by DNA microarray experiments produce considerably more data than other techniques, and require a wide variety of computational techniques for identifying patterns of expression that may be biologically significant. These will have to be verified and validated by comparison to results from other methods, integrated with other systems data, and provide the feedback for further experimentation for testing mechanistic or other biological hypotheses.

Cancer is a world-famous deadly disease. According to the World Health Organization (WHO), cancer is the second leading cause of death globally and is responsible for an estimated 9.6 million deaths in 2018. One well-known technique for cancer detection is the DNA microarray technique. DNA microarray technology provides an opportunity for researchers to analyze thousands of gene expression profiles at the same time to determine whether a person has cancer or not. However, one of the problems in DNA microarray data is the large number of features that require feature selection. In overcoming these problems, this study will use the feature selection Support Vector Machine-Recursive Feature Elimination (SVM-RFE) and Chi-Square and use the Naive Bayes classification method. The accuracy results from using feature selection with those that are not will be compared. The accuracy between using the two feature selection methods will also be compared to find which feature selection method is better when combined with the Naive Bayes classification method. To get an overall picture of the performance comparison, this study also considers precision, recall, and F1-score. The best accuracy results obtained were 100% lung cancer data with SVM-RFE and Chi-Square, 99.6% ovarian cancer with SVM-RFE, 93.7% breast cancer with SVM-RFE, and 90% colon cancer with SVM- RFE.

DNA microarray SNP associations with clinical efficacy and side effects of domperidone treatment for gastroparesis

High-throughput molecular-profiling technologies provide rapid, efficient and systematic approaches to search for biomarkers. Supervised learning algorithms are naturally suited to analyse a large amount of data generated using these technologies in biomarker discovery efforts. The study demonstrates with two examples a data-driven analysis approach to analysis of large complicated datasets collected in high-throughput technologies in the context of biomarker discovery. The approach consists of two analytic steps: an initial unsupervised analysis to obtain accurate knowledge about sample clustering, followed by a second supervised analysis to identify a small set of putative biomarkers for further experimental characterization. By comparing the most widely applied clustering algorithms using a leukaemia DNA microarray dataset, it was established that principal component analysis-assisted projections of samples from a high-dimensional molecular feature space into a few low dimensional subspaces provides a more effective and accurate way to explore visually and identify data structures that confirm intended experimental effects based on expected group membership. A supervised analysis method, shrunken centroid algorithm, was chosen to take knowledge of sample clustering gained or confirmed by the first step of the analysis to identify a small set of molecules as candidate biomarkers for further experimentation. The approach was applied to two molecular-profiling studies. In the first study, PCA-assisted analysis of DNA microarray data revealed that discrete data structures exist in rat liver gene expression and correlated with blood clinical chemistry and liver pathological damage in response to a chemical toxicant diethylhexylphthalate, a peroxisome-proliferator-activator receptor agonist. Sixteen genes were then identified by shrunken centroid algorithm as the best candidate biomarkers for liver damage. Functional annotations of these genes revealed roles in acute phase response, lipid and fatty acid metabolism and they are functionally relevant to the observed toxicities. In the second study, 26 urine ions identified from a GC/MS spectrum, two of which were glucose fragment ions included as positive controls, showed robust changes with the development of diabetes in Zucker diabetic fatty rats. Further experiments are needed to define their chemical identities and establish functional relevancy to disease development.

Zeroing in on the “holy grail”

BackgroundNumerous microarray analysis programs have been created through the efforts of Open Source software development projects. Providing browser-based interfaces that allow these programs to be executed over the Internet enhances the applicability and utility of these analytic software tools.ResultsHere we present ArrayQuest, a web-based DNA microarray analysis process controller. Key features of ArrayQuest are that (1) it is capable of executing numerous analysis programs such as those written in R, BioPerl and C++; (2) new analysis programs can be added to ArrayQuest Methods Library at the request of users or developers; (3) input DNA microarray data can be selected from public databases (i.e., the Medical University of South Carolina (MUSC) DNA Microarray Database or Gene Expression Omnibus (GEO)) or it can be uploaded to the ArrayQuest center-point web server into a password-protected area; and (4) analysis jobs are distributed across computers configured in a backend cluster. To demonstrate the utility of ArrayQuest we have populated the methods library with methods for analysis of Affymetrix DNA microarray data.ConclusionArrayQuest enables browser-based implementation of DNA microarray data analysis programs that can be executed on a Linux-based platform. Importantly, ArrayQuest is a platform that will facilitate the distribution and implementation of new analysis algorithms and is therefore of use to both developers of analysis applications as well as users. ArrayQuest is freely available for use at .

DNA microarray technology is a fundamental tool in gene expression data analysis. The collection of datasets from the technology has underscored the need for quantitative analytical tools to examine such data. Due to the large number of genes and complex gene regulation networks, clustering is a useful exploratory technique for analyzing these data. Many clustering algorithms have been proposed to analyze microarray gene expression data, but very few of them evaluate the quality of the clusters. In this paper, a novel cluster analysis technique has been proposed without considering number of clusters a priori. The method computes a similarity measurement function based on which the clusters are merged and subsequently splits a cluster by computing the degree of separation of the cluster. The process of splitting and merging performs iteratively until the cluster validity index (i.e. DB index) degrades. The experimental result shows that the proposed cluster analysis technique gives comparable results on gene cancer dataset with existing methods. This study may help raise relevant issues in the extraction of meaningful biological information from microarray expression data. Keywords- DNA microarray data, Clustering technique, Cluster validity index, Similarity measurement, Splitting and Merging, Cancer data analysis

In the past decade, DNA microarrays have fundamentally changed the way we study complex biological systems. By measuring the expression levels of thousands of transcripts, the paradigm of studying organisms has shifted from focusing on the local phenomena of a few genes to surveying the whole genome. DNA microarrays are used in a variety of ways, from simple comparisons between two samples to more intricate time-series studies. With the large number of genes being studied, the dimensionality of the problem is inevitably high. The analysis of microarray data thus requires specific approaches. In the case of time-series microarray studies, data analysis is further complicated by the correlation between successive time points in a series.In this review, we survey the methodologies used in the analysis of static and time-series microarray data, covering data pre-processing, identification of differentially expressed genes, profile pattern recognition, pathway analysis, and network reconstruction. When available, examples of their use in mammalian cell cultures are presented.

Cancer is one of the major causes of deaths worldwide. This disease is more ghastly as it doesn’t announce itself until it reaches in an advance stage. Still, mortality rate for cancer can be decreased if we diagnose & provide treatment at earliest. Though there are traditional clinical trials to predict a cancer there does not a single test which can correctly identify this disease. In the recent years DNA Microarray technology has been significantly used to analyze & predict the cancer. Analysis of gene expressions is not only interesting but also challenging as it is not only the concern of accuracy but also matter of life or death of a patient. DNA Microarray data is high dimensional, noisy & redundant, it makes task of classification more complicated as high computational cost is involved. Therefore feature selection & feature reduction becomes important task prior to classification. This paper presents comparative performance analysis of different dimensionality reduction techniques implemented on TCGA PANCANCER dataset.