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.

On Truncated Versions of Certain Measures of Inequality and Stability

The present study focuses attention on defining certain measures of income inequality for the truncated distributions and characterization of probability distributions using the functional form of these measures, extension of some measures of inequality and stability to higher dimensions, characterization of bivariate models using the above concepts and estimation of some measures of inequality using the Bayesian techniques. The thesis defines certain measures of income inequality for the truncated distributions and studies the effect of truncation upon these measures. An important measure used in Reliability theory, to measure the stability of the component is the residual entropy function. This concept can advantageously used as a measure of inequality of truncated distributions. The geometric mean comes up as handy tool in the measurement of income inequality. The geometric vitality function being the geometric mean of the truncated random variable can be advantageously utilized to measure inequality of the truncated distributions. The study includes problem of estimation of the Lorenz curve, Gini-index and variance of logarithms for the Pareto distribution using Bayesian techniques.

Characterization of Probability Distributions Using the Residual Entropy Function

The present study on the characterization of probability distributions using the residual entropy function. The concept of entropy is extensively used in literature as a quantitative measure of uncertainty associated with a random phenomenon. The commonly used life time models in reliability Theory are exponential distribution, Pareto distribution, Beta distribution, Weibull distribution and gamma distribution. Several characterization theorems are obtained for the above models using reliability concepts such as failure rate, mean residual life function, vitality function, variance residual life function etc. Most of the works on characterization of distributions in the reliability context centers around the failure rate or the residual life function. The important aspect of interest in the study of entropy is that of locating distributions for which the shannon’s entropy is maximum subject to certain restrictions on the underlying random variable. The geometric vitality function and examine its properties. It is established that the geometric vitality function determines the distribution uniquely. The problem of averaging the residual entropy function is examined, and also the truncated form version of entropies of higher order are defined. In this study it is established that the residual entropy function determines the distribution uniquely and that the constancy of the same is characteristics to the geometric distribution

Characterization of Probability Distributions by Variance Bounds and its Applications

Department of Statistics, Cochin University of Science and Technology

Modeling and Analysis of Some Heavy Tailed Time Series

The thesis has covered various aspects of modeling and analysis of finite mean time series with symmetric stable distributed innovations. Time series analysis based on Box and Jenkins methods are the most popular approaches where the models are linear and errors are Gaussian. We highlighted the limitations of classical time series analysis tools and explored some generalized tools and organized the approach parallel to the classical set up. In the present thesis we mainly studied the estimation and prediction of signal plus noise model. Here we assumed the signal and noise follow some models with symmetric stable innovations.We start the thesis with some motivating examples and application areas of alpha stable time series models. Classical time series analysis and corresponding theories based on finite variance models are extensively discussed in second chapter. We also surveyed the existing theories and methods correspond to infinite variance models in the same chapter. We present a linear filtering method for computing the filter weights assigned to the observation for estimating unobserved signal under general noisy environment in third chapter. Here we consider both the signal and the noise as stationary processes with infinite variance innovations. We derived semi infinite, double infinite and asymmetric signal extraction filters based on minimum dispersion criteria. Finite length filters based on Kalman-Levy filters are developed and identified the pattern of the filter weights. Simulation studies show that the proposed methods are competent enough in signal extraction for processes with infinite variance.Parameter estimation of autoregressive signals observed in a symmetric stable noise environment is discussed in fourth chapter. Here we used higher order Yule-Walker type estimation using auto-covariation function and exemplify the methods by simulation and application to Sea surface temperature data. We increased the number of Yule-Walker equations and proposed a ordinary least square estimate to the autoregressive parameters. Singularity problem of the auto-covariation matrix is addressed and derived a modified version of the Generalized Yule-Walker method using singular value decomposition.In fifth chapter of the thesis we introduced partial covariation function as a tool for stable time series analysis where covariance or partial covariance is ill defined. Asymptotic results of the partial auto-covariation is studied and its application in model identification of stable auto-regressive models are discussed. We generalize the Durbin-Levinson algorithm to include infinite variance models in terms of partial auto-covariation function and introduce a new information criteria for consistent order estimation of stable autoregressive model.In chapter six we explore the application of the techniques discussed in the previous chapter in signal processing. Frequency estimation of sinusoidal signal observed in symmetric stable noisy environment is discussed in this context. Here we introduced a parametric spectrum analysis and frequency estimate using power transfer function. Estimate of the power transfer function is obtained using the modified generalized Yule-Walker approach. Another important problem in statistical signal processing is to identify the number of sinusoidal components in an observed signal. We used a modified version of the proposed information criteria for this purpose.

Drastic variation in the surface boundary layer parameters over Cochin during the annular solar eclipse: Analysis using sonic anemometer data

Atmospheric surface boundary layer parameters vary anomalously in response to the occurrence of annular solar eclipse on 15th January 2010 over Cochin. It was the longest annular solar eclipse occurred over South India with high intensity. As it occurred during the noon hours, it is considered to be much more significant because of its effects in all the regions of atmosphere including ionosphere. Since the insolation is the main driving factor responsible for the anomalous changes occurred in the surface layer due to annular solar eclipse, occurred on 15th January 2010, that played very important role in understanding dynamics of the atmosphere during the eclipse period because of its coincidence with the noon time. The Sonic anemometer is able to give data of zonal, meridional and vertical wind as well as the air temperature at a temporal resolution of 1 s. Different surface boundary layer parameters and turbulent fluxes were computed by the application of eddy correlation technique using the high resolution station data. The surface boundary layer parameters that are computed using the sonic anemometer data during the period are momentum flux, sensible heat flux, turbulent kinetic energy, frictional velocity (u*), variance of temperature, variances of u, v and w wind. In order to compare the results, a control run has been done using the data of previous day as well as next day. It is noted that over the specified time period of annular solar eclipse, all the above stated surface boundary layer parameters vary anomalously when compared with the control run. From the observations we could note that momentum flux was 0.1 Nm 2 instead of the mean value 0.2 Nm-2 when there was eclipse. Sensible heat flux anomalously decreases to 50 Nm 2 instead of the mean value 200 Nm 2 at the time of solar eclipse. The turbulent kinetic energy decreases to 0.2 m2s 2 from the mean value 1 m2s 2. The frictional velocity value decreases to 0.05 ms 1 instead of the mean value 0.2 ms 1. The present study aimed at understanding the dynamics of surface layer in response to the annular solar eclipse over a tropical coastal station, occurred during the noon hours. Key words: annular solar eclipse, surface boundary layer, sonic anemometer

A Novel Decision Tree Algorithm for Numeric Datasets - C 4.5*Stat

Decision trees are very powerful tools for classification in data mining tasks that involves different types of attributes. When coming to handling numeric data sets, usually they are converted first to categorical types and then classified using information gain concepts. Information gain is a very popular and useful concept which tells you, whether any benefit occurs after splitting with a given attribute as far as information content is concerned. But this process is computationally intensive for large data sets. Also popular decision tree algorithms like ID3 cannot handle numeric data sets. This paper proposes statistical variance as an alternative to information gain as well as statistical mean to split attributes in completely numerical data sets. The new algorithm has been proved to be competent with respect to its information gain counterpart C4.5 and competent with many existing decision tree algorithms against the standard UCI benchmarking datasets using the ANOVA test in statistics. The specific advantages of this proposed new algorithm are that it avoids the computational overhead of information gain computation for large data sets with many attributes, as well as it avoids the conversion to categorical data from huge numeric data sets which also is a time consuming task. So as a summary, huge numeric datasets can be directly submitted to this algorithm without any attribute mappings or information gain computations. It also blends the two closely related fields statistics and data mining

Identification of models using failure rate and mean residual life of doubly truncated random variables

In this paper, we study the relationship between the failure rate and the mean residual life of doubly truncated random variables. Accordingly, we develop characterizations for exponential, Pareto 11 and beta distributions. Further, we generalize the identities for fire Pearson and the exponential family of distributions given respectively in Nair and Sankaran (1991) and Consul (1995). Applications of these measures in file context of lengthbiased models are also explored

Dominant Mean Percentage Score Factors Of The Consumer Purchase Behaviour Of Passenger Cars

Globalization and liberalization, with the entry of many prominent foreign manufacturers, changed the automobile scenario in India, since early 1990’s. World Leaders in automobile manufacturing such as Ford, General Motors, Honda, Toyota, Suzuki, Hyundai, Renault, Mitsubishi, Benz, BMW, Volkswagen and Nissan set up their manufacturing units in India in joint venture with their Indian counterpart companies, by making use of the Foreign Direct Investment policy of the Government of India, These manufacturers started capturing the hearts of Indian car customers with their choice of technological and innovative product features, with quality and reliability. With the multiplicity of choices available to the Indian passenger car buyers, it drastically changed the way the car purchase scenario in India and particularly in the State of Kerala. This transformed the automobile scene from a sellers’ market to buyers’ market. Car customers started developing their own personal preferences and purchasing patterns, which were hitherto unknown in the Indian automobile segment. The main purpose of this paper is to come up with the identification of possible parameters and a framework development, that influence the consumer purchase behaviour patterns of passenger car owners in the State of Kerala, so that further research could be done, based on the framework and the identified parameters.

ECG Noise Removal using GA tuned Sign-Data Least Mean Square Algorithm

Adaptive filter is a primary method to filter Electrocardiogram (ECG), because it does not need the signal statistical characteristics. In this paper, an adaptive filtering technique for denoising the ECG based on Genetic Algorithm (GA) tuned Sign-Data Least Mean Square (SD-LMS) algorithm is proposed. This technique minimizes the mean-squared error between the primary input, which is a noisy ECG, and a reference input which can be either noise that is correlated in some way with the noise in the primary input or a signal that is correlated only with ECG in the primary input. Noise is used as the reference signal in this work. The algorithm was applied to the records from the MIT -BIH Arrhythmia database for removing the baseline wander and 60Hz power line interference. The proposed algorithm gave an average signal to noise ratio improvement of 10.75 dB for baseline wander and 24.26 dB for power line interference which is better than the previous reported works

A New Fast Fractal Modeling Approach for the Detection of Microcalcifications in Mammograms

In this paper, a novel fast method for modeling mammograms by deterministic fractal coding approach to detect the presence of microcalcifications, which are early signs of breast cancer, is presented. The modeled mammogram obtained using fractal encoding method is visually similar to the original image containing microcalcifications, and therefore, when it is taken out from the original mammogram, the presence of microcalcifications can be enhanced. The limitation of fractal image modeling is the tremendous time required for encoding. In the present work, instead of searching for a matching domain in the entire domain pool of the image, three methods based on mean and variance, dynamic range of the image blocks, and mass center features are used. This reduced the encoding time by a factor of 3, 89, and 13, respectively, in the three methods with respect to the conventional fractal image coding method with quad tree partitioning. The mammograms obtained from The Mammographic Image Analysis Society database (ground truth available) gave a total detection score of 87.6%, 87.6%, 90.5%, and 87.6%, for the conventional and the proposed three methods, respectively.