Mean Squared Residue Based Biclustering Algorithms for the Analysis of Gene Expression Data

Computational Biology is the research are that contributes to the analysis of biological data through the development of algorithms which will address significant research problems.The data from molecular biology includes DNA,RNA ,Protein and Gene expression data.Gene Expression Data provides the expression level of genes under different conditions.Gene expression is the process of transcribing the DNA sequence of a gene into mRNA sequences which in turn are later translated into proteins.The number of copies of mRNA produced is called the expression level of a gene.Gene expression data is organized in the form of a matrix. Rows in the matrix represent genes and columns in the matrix represent experimental conditions.Experimental conditions can be different tissue types or time points.Entries in the gene expression matrix are real values.Through the analysis of gene expression data it is possible to determine the behavioral patterns of genes such as similarity of their behavior,nature of their interaction,their respective contribution to the same pathways and so on. Similar expression patterns are exhibited by the genes participating in the same biological process.These patterns have immense relevance and application in bioinformatics and clinical research.Theses patterns are used in the medical domain for aid in more accurate diagnosis,prognosis,treatment planning.drug discovery and protein network analysis.To identify various patterns from gene expression data,data mining techniques are essential.Clustering is an important data mining technique for the analysis of gene expression data.To overcome the problems associated with clustering,biclustering is introduced.Biclustering refers to simultaneous clustering of both rows and columns of a data matrix. Clustering is a global whereas biclustering is a local model.Discovering local expression patterns is essential for identfying many genetic pathways that are not apparent otherwise.It is therefore necessary to move beyond the clustering paradigm towards developing approaches which are capable of discovering local patterns in gene expression data.A biclusters is a submatrix of the gene expression data matrix.The rows and columns in the submatrix need not be contiguous as in the gene expression data matrix.Biclusters are not disjoint.Computation of biclusters is costly because one will have to consider all the combinations of columans and rows in order to find out all the biclusters.The search space for the biclustering problem is 2 m+n where m and n are the number of genes and conditions respectively.Usually m+n is more than 3000.The biclustering problem is NP-hard.Biclustering is a powerful analytical tool for the biologist.The research reported in this thesis addresses the problem of biclustering.Ten algorithms are developed for the identification of coherent biclusters from gene expression data.All these algorithms are making use of a measure called mean squared residue to search for biclusters.The objective here is to identify the biclusters of maximum size with the mean squared residue lower than a given threshold. All these algorithms begin the search from tightly coregulated submatrices called the seeds.These seeds are generated by K-Means clustering algorithm.The algorithms developed can be classified as constraint based,greedy and metaheuristic.Constarint based algorithms uses one or more of the various constaints namely the MSR threshold and the MSR difference threshold.The greedy approach makes a locally optimal choice at each stage with the objective of finding the global optimum.In metaheuristic approaches particle Swarm Optimization(PSO) and variants of Greedy Randomized Adaptive Search Procedure(GRASP) are used for the identification of biclusters.These algorithms are implemented on the Yeast and Lymphoma datasets.Biologically relevant and statistically significant biclusters are identified by all these algorithms which are validated by Gene Ontology database.All these algorithms are compared with some other biclustering algorithms.Algorithms developed in this work overcome some of the problems associated with the already existing algorithms.With the help of some of the algorithms which are developed in this work biclusters with very high row variance,which is higher than the row variance of any other algorithm using mean squared residue, are identified from both Yeast and Lymphoma data sets.Such biclusters which make significant change in the expression level are highly relevant biologically.

Development of Techniques for the Automatic Extraction and Grade Detection of Glioma Tumors from Conventional Brain Magnetic Resonant Images

Cerebral glioma is the most prevalent primary brain tumor, which are classified broadly into low and high grades according to the degree of malignancy. High grade gliomas are highly malignant which possess a poor prognosis, and the patients survive less than eighteen months after diagnosis. Low grade gliomas are slow growing, least malignant and has better response to therapy. To date, histological grading is used as the standard technique for diagnosis, treatment planning and survival prediction. The main objective of this thesis is to propose novel methods for automatic extraction of low and high grade glioma and other brain tissues, grade detection techniques for glioma using conventional magnetic resonance imaging (MRI) modalities and 3D modelling of glioma from segmented tumor slices in order to assess the growth rate of tumors. Two new methods are developed for extracting tumor regions, of which the second method, named as Adaptive Gray level Algebraic set Segmentation Algorithm (AGASA) can also extract white matter and grey matter from T1 FLAIR an T2 weighted images. The methods were validated with manual Ground truth images, which showed promising results. The developed methods were compared with widely used Fuzzy c-means clustering technique and the robustness of the algorithm with respect to noise is also checked for different noise levels. Image texture can provide significant information on the (ab)normality of tissue, and this thesis expands this idea to tumour texture grading and detection. Based on the thresholds of discriminant first order and gray level cooccurrence matrix based second order statistical features three feature sets were formulated and a decision system was developed for grade detection of glioma from conventional T2 weighted MRI modality.The quantitative performance analysis using ROC curve showed 99.03% accuracy for distinguishing between advanced (aggressive) and early stage (non-aggressive) malignant glioma. The developed brain texture analysis techniques can improve the physician’s ability to detect and analyse pathologies leading to a more reliable diagnosis and treatment of disease. The segmented tumors were also used for volumetric modelling of tumors which can provide an idea of the growth rate of tumor; this can be used for assessing response to therapy and patient prognosis.

Biclustering Gene Expression Data using MSR Difference Threshold

Biclustering is simultaneous clustering of both rows and columns of a data matrix. A measure called Mean Squared Residue (MSR) is used to simultaneously evaluate the coherence of rows and columns within a submatrix. In this paper a novel algorithm is developed for biclustering gene expression data using the newly introduced concept of MSR difference threshold. In the first step high quality bicluster seeds are generated using K-Means clustering algorithm. Then more genes and conditions (node) are added to the bicluster. Before adding a node the MSR X of the bicluster is calculated. After adding the node again the MSR Y is calculated. The added node is deleted if Y minus X is greater than MSR difference threshold or if Y is greater than MSR threshold which depends on the dataset. The MSR difference threshold is different for gene list and condition list and it depends on the dataset also. Proper values should be identified through experimentation in order to obtain biclusters of high quality. The results obtained on bench mark dataset clearly indicate that this algorithm is better than many of the existing biclustering algorithms

Brain Tissue Classification from Multispectral MRI by Wavelet based Principal Component Analysis

In this paper, we propose a multispectral analysis system using wavelet based Principal Component Analysis (PCA), to improve the brain tissue classification from MRI images. Global transforms like PCA often neglects significant small abnormality details, while dealing with a massive amount of multispectral data. In order to resolve this issue, input dataset is expanded by detail coefficients from multisignal wavelet analysis. Then, PCA is applied on the new dataset to perform feature analysis. Finally, an unsupervised classification with Fuzzy C-Means clustering algorithm is used to measure the improvement in reproducibility and accuracy of the results. A detailed comparative analysis of classified tissues with those from conventional PCA is also carried out. Proposed method yielded good improvement in classification of small abnormalities with high sensitivity/accuracy values, 98.9/98.3, for clinical analysis. Experimental results from synthetic and clinical data recommend the new method as a promising approach in brain tissue analysis.

Wavelet based Independent Component Analysis for Multispectral Brain Tissue Classification

Multispectral analysis is a promising approach in tissue classification and abnormality detection from Magnetic Resonance (MR) images. But instability in accuracy and reproducibility of the classification results from conventional techniques keeps it far from clinical applications. Recent studies proposed Independent Component Analysis (ICA) as an effective method for source signals separation from multispectral MR data. However, it often fails to extract the local features like small abnormalities, especially from dependent real data. A multisignal wavelet analysis prior to ICA is proposed in this work to resolve these issues. Best de-correlated detail coefficients are combined with input images to give better classification results. Performance improvement of the proposed method over conventional ICA is effectively demonstrated by segmentation and classification using k-means clustering. Experimental results from synthetic and real data strongly confirm the positive effect of the new method with an improved Tanimoto index/Sensitivity values, 0.884/93.605, for reproduced small white matter lesions

Automatic Image Annotation Using SURF Descriptors

In recent years there is an apparent shift in research from content based image retrieval (CBIR) to automatic image annotation in order to bridge the gap between low level features and high level semantics of images. Automatic Image Annotation (AIA) techniques facilitate extraction of high level semantic concepts from images by machine learning techniques. Many AIA techniques use feature analysis as the first step to identify the objects in the image. However, the high dimensional image features make the performance of the system worse. This paper describes and evaluates an automatic image annotation framework which uses SURF descriptors to select right number of features and right features for annotation. The proposed framework uses a hybrid approach in which k-means clustering is used in the training phase and fuzzy K-NN classification in the annotation phase. The performance of the system is evaluated using standard metrics.

Automatic Optic Disc Boundary Extraction from Color Fundus Images

Efficient optic disc segmentation is an important task in automated retinal screening. For the same reason optic disc detection is fundamental for medical references and is important for the retinal image analysis application. The most difficult problem of optic disc extraction is to locate the region of interest. Moreover it is a time consuming task. This paper tries to overcome this barrier by presenting an automated method for optic disc boundary extraction using Fuzzy C Means combined with thresholding. The discs determined by the new method agree relatively well with those determined by the experts. The present method has been validated on a data set of 110 colour fundus images from DRION database, and has obtained promising results. The performance of the system is evaluated using the difference in horizontal and vertical diameters of the obtained disc boundary and that of the ground truth obtained from two expert ophthalmologists. For the 25 test images selected from the 110 colour fundus images, the Pearson correlation of the ground truth diameters with the detected diameters by the new method are 0.946 and 0.958 and, 0.94 and 0.974 respectively. From the scatter plot, it is shown that the ground truth and detected diameters have a high positive correlation. This computerized analysis of optic disc is very useful for the diagnosis of retinal diseases

SPATIAL CLUSTERING ALGORITHMS-AN OVERVIEW.

An Overview of known spatial clustering algorithms The space of interest can be the two-dimensional abstraction of the surface of the earth or a man-made space like the layout of a VLSI design, a volume containing a model of the human brain, or another 3d-space representing the arrangement of chains of protein molecules. The data consists of geometric information and can be either discrete or continuous. The explicit location and extension of spatial objects define implicit relations of spatial neighborhood (such as topological, distance and direction relations) which are used by spatial data mining algorithms. Therefore, spatial data mining algorithms are required for spatial characterization and spatial trend analysis. Spatial data mining or knowledge discovery in spatial databases differs from regular data mining in analogous with the differences between non-spatial data and spatial data. The attributes of a spatial object stored in a database may be affected by the attributes of the spatial neighbors of that object. In addition, spatial location, and implicit information about the location of an object, may be exactly the information that can be extracted through spatial data mining

Detection of Flock Movement in Spatio-Temporal Database using Clustering Techniques - an Experience

In this paper, moving flock patterns are mined from spatio- temporal datasets by incorporating a clustering algorithm. A flock is defined as the set of data that move together for a certain continuous amount of time. Finding out moving flock patterns using clustering algorithms is a potential method to find out frequent patterns of movement in large trajectory datasets. In this approach, SPatial clusteRing algoRithm thrOugh sWarm intelligence (SPARROW) is the clustering algorithm used. The advantage of using SPARROW algorithm is that it can effectively discover clusters of widely varying sizes and shapes from large databases. Variations of the proposed method are addressed and also the experimental results show that the problem of scalability and duplicate pattern formation is addressed. This method also reduces the number of patterns produced

Significance Of Classification Techniques In Prediction Of Learning Disabilities

The aim of this study is to show the importance of two classification techniques, viz. decision tree and clustering, in prediction of learning disabilities (LD) of school-age children. LDs affect about 10 percent of all children enrolled in schools. The problems of children with specific learning disabilities have been a cause of concern to parents and teachers for some time. Decision trees and clustering are powerful and popular tools used for classification and prediction in Data mining. Different rules extracted from the decision tree are used for prediction of learning disabilities. Clustering is the assignment of a set of observations into subsets, called clusters, which are useful in finding the different signs and symptoms (attributes) present in the LD affected child. In this paper, J48 algorithm is used for constructing the decision tree and K-means algorithm is used for creating the clusters. By applying these classification techniques, LD in any child can be identified

Spectral clustering independent component analysis for tissue classification from brain MRI

A spectral angle based feature extraction method, Spectral Clustering Independent Component Analysis (SC-ICA), is proposed in this work to improve the brain tissue classification from Magnetic Resonance Images (MRI). SC-ICA provides equal priority to global and local features; thereby it tries to resolve the inefficiency of conventional approaches in abnormal tissue extraction. First, input multispectral MRI is divided into different clusters by a spectral distance based clustering. Then, Independent Component Analysis (ICA) is applied on the clustered data, in conjunction with Support Vector Machines (SVM) for brain tissue analysis. Normal and abnormal datasets, consisting of real and synthetic T1-weighted, T2-weighted and proton density/fluid-attenuated inversion recovery images, were used to evaluate the performance of the new method. Comparative analysis with ICA based SVM and other conventional classifiers established the stability and efficiency of SC-ICA based classification, especially in reproduction of small abnormalities. Clinical abnormal case analysis demonstrated it through the highest Tanimoto Index/accuracy values, 0.75/98.8%, observed against ICA based SVM results, 0.17/96.1%, for reproduced lesions. Experimental results recommend the proposed method as a promising approach in clinical and pathological studies of brain diseases

Development of Hierarchical Clustering Techniques for Gridded Data from Mixed Data Sequences

Knowledge discovery in databases is the non-trivial process of identifying valid, novel potentially useful and ultimately understandable patterns from data. The term Data mining refers to the process which does the exploratory analysis on the data and builds some model on the data. To infer patterns from data, data mining involves different approaches like association rule mining, classification techniques or clustering techniques. Among the many data mining techniques, clustering plays a major role, since it helps to group the related data for assessing properties and drawing conclusions. Most of the clustering algorithms act on a dataset with uniform format, since the similarity or dissimilarity between the data points is a significant factor in finding out the clusters. If a dataset consists of mixed attributes, i.e. a combination of numerical and categorical variables, a preferred approach is to convert different formats into a uniform format. The research study explores the various techniques to convert the mixed data sets to a numerical equivalent, so as to make it equipped for applying the statistical and similar algorithms. The results of clustering mixed category data after conversion to numeric data type have been demonstrated using a crime data set. The thesis also proposes an extension to the well known algorithm for handling mixed data types, to deal with data sets having only categorical data. The proposed conversion has been validated on a data set corresponding to breast cancer. Moreover, another issue with the clustering process is the visualization of output. Different geometric techniques like scatter plot, or projection plots are available, but none of the techniques display the result projecting the whole database but rather demonstrate attribute-pair wise analysis