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.

Information Discovery in Distributed Systems-A Novel Concept Based on Modelling of Information Elements

Sharing of information with those in need of it has always been an idealistic goal of networked environments. With the proliferation of computer networks, information is so widely distributed among systems, that it is imperative to have well-organized schemes for retrieval and also discovery. This thesis attempts to investigate the problems associated with such schemes and suggests a software architecture, which is aimed towards achieving a meaningful discovery. Usage of information elements as a modelling base for efficient information discovery in distributed systems is demonstrated with the aid of a novel conceptual entity called infotron.The investigations are focused on distributed systems and their associated problems. The study was directed towards identifying suitable software architecture and incorporating the same in an environment where information growth is phenomenal and a proper mechanism for carrying out information discovery becomes feasible. An empirical study undertaken with the aid of an election database of constituencies distributed geographically, provided the insights required. This is manifested in the Election Counting and Reporting Software (ECRS) System. ECRS system is a software system, which is essentially distributed in nature designed to prepare reports to district administrators about the election counting process and to generate other miscellaneous statutory reports.Most of the distributed systems of the nature of ECRS normally will possess a "fragile architecture" which would make them amenable to collapse, with the occurrence of minor faults. This is resolved with the help of the penta-tier architecture proposed, that contained five different technologies at different tiers of the architecture.The results of experiment conducted and its analysis show that such an architecture would help to maintain different components of the software intact in an impermeable manner from any internal or external faults. The architecture thus evolved needed a mechanism to support information processing and discovery. This necessitated the introduction of the noveI concept of infotrons. Further, when a computing machine has to perform any meaningful extraction of information, it is guided by what is termed an infotron dictionary.The other empirical study was to find out which of the two prominent markup languages namely HTML and XML, is best suited for the incorporation of infotrons. A comparative study of 200 documents in HTML and XML was undertaken. The result was in favor ofXML.The concept of infotron and that of infotron dictionary, which were developed, was applied to implement an Information Discovery System (IDS). IDS is essentially, a system, that starts with the infotron(s) supplied as clue(s), and results in brewing the information required to satisfy the need of the information discoverer by utilizing the documents available at its disposal (as information space). The various components of the system and their interaction follows the penta-tier architectural model and therefore can be considered fault-tolerant. IDS is generic in nature and therefore the characteristics and the specifications were drawn up accordingly. Many subsystems interacted with multiple infotron dictionaries that were maintained in the system.In order to demonstrate the working of the IDS and to discover the information without modification of a typical Library Information System (LIS), an Information Discovery in Library Information System (lDLIS) application was developed. IDLIS is essentially a wrapper for the LIS, which maintains all the databases of the library. The purpose was to demonstrate that the functionality of a legacy system could be enhanced with the augmentation of IDS leading to information discovery service. IDLIS demonstrates IDS in action. IDLIS proves that any legacy system could be augmented with IDS effectively to provide the additional functionality of information discovery service.Possible applications of IDS and scope for further research in the field are covered.

Information discovery in distributed systems - A novel concept based on modelling of information elements

This thesis attempts to investigate the problems associated with such schemes and suggests a software architecture, which is aimed towards achieving a meaningful discovery. Usage of information elements as a modelling base for efficient information discovery in distributed systems is demonstrated with the aid of a novel conceptual entity called infotron. The investigations are focused on distributed systems and their associated problems. The study was directed towards identifying suitable software architecture and incorporating the same in an environment where information growth is phenomenal and a proper mechanism for carrying out information discovery becomes feasible. An empirical study undertaken with the aid of an election database of constituencies distributed geographically, provided the insights required. This is manifested in the Election Counting and Reporting Software (ECRS) System. ECRS system is a software system, which is essentially distributed in nature designed to prepare reports to district administrators about the election counting process and to generate other miscellaneous statutory reports.

Modelling and Analysis of Some Time Series

The thesis deals with some of the non-linear Gaussian and non-Gaussian time models and mainly concentrated in studying the properties and application of a first order autoregressive process with Cauchy marginal distribution. In this thesis some of the non-linear Gaussian and non-Gaussian time series models and mainly concentrated in studying the properties and application of a order autoregressive process with Cauchy marginal distribution. Time series relating to prices, consumptions, money in circulation, bank deposits and bank clearing, sales and profit in a departmental store, national income and foreign exchange reserves, prices and dividend of shares in a stock exchange etc. are examples of economic and business time series. The thesis discuses the application of a threshold autoregressive(TAR) model, try to fit this model to a time series data. Another important non-linear model is the ARCH model, and the third model is the TARCH model. The main objective here is to identify an appropriate model to a given set of data. The data considered are the daily coconut oil prices for a period of three years. Since it is a price data the consecutive prices may not be independent and hence a time series based model is more appropriate. In this study the properties like ergodicity, mixing property and time reversibility and also various estimation procedures used to estimate the unknown parameters of the process.

Mathematical Modelling of the Dynamics of Granular Materials in a Rotating Cylinder

The current study is aimed at the development of a theoretical simulation tool based on Discrete Element Method (DEM) to 'interpret granular dynamics of solid bed in the cross section of the horizontal rotating cylinder at the microscopic level and subsequently apply this model to establish the transition behaviour, mixing and segregation.The simulation of the granular motion developed in this work is based on solving Newton's equation of motion for each particle in the granular bed subjected to the collisional forces, external forces and boundary forces. At every instant of time, the forces are tracked and the positions velocities and accelarations of each partcle is The software code for this simulation is written in VISUAL FORTRAN 90 After checking the validity of the code with special tests, it is used to investigate the transition behaviour of granular solids motion in the cross section of a rotating cylinder for various rotational speeds and fill fraction.This work is hence directed towards a theoretical investigation based on Discrete Element Method (DEM) of the motion of granular solids in the radial direction of the horizontal cylinder to elucidate the relationship between the operating parameters of the rotating cylinder geometry and physical properties ofthe granular solid.The operating parameters of the rotating cylinder include the various rotational velocities of the cylinder and volumetric fill. The physical properties of the granular solids include particle sizes, densities, stiffness coefficients, and coefficient of friction Further the work highlights the fundamental basis for the important phenomena of the system namely; (i) the different modes of solids motion observed in a transverse crosssection of the rotating cylinder for various rotational speeds, (ii) the radial mixing of the granular solid in terms of active layer depth (iii) rate coefficient of mixing as well as the transition behaviour in terms of the bed turnover time and rotational speed and (iv) the segregation mechanisms resulting from differences in the size and density of particles.The transition behaviour involving its six different modes of motion of the granular solid bed is quantified in terms of Froude number and the results obtained are validated with experimental and theoretical results reported in the literature The transition from slumping to rolling mode is quantified using the bed turnover time and a linear relationship is established between the bed turn over time and the inverse of the rotational speed of the cylinder as predicted by Davidson et al. [2000]. The effect of the rotational speed, fill fraction and coefficient of friction on the dynamic angle of repose are presented and discussed. The variation of active layer depth with respect to fill fraction and rotational speed have been investigated. The results obtained through simulation are compared with the experimental results reported by Van Puyvelde et. at. [2000] and Ding et at. [2002].The theoretical model has been further extended, to study the rmxmg and segregation in the transverse direction for different particle sizes and their size ratios. The effect of fill fraction and rotational speed on the transverse mixing behaviour is presented in the form of a mixing index and mixing kinetics curve. The segregation pattern obtained by the simulation of the granular solid bed with respect to the rotational speed of the cylinder is presented both in graphical and numerical forms. The segregation behaviour of the granular solid bed with respect to particle size, density and volume fraction of particle size has been investigated. Several important macro parameters characterising segregation such as mixing index, percolation index and segregation index have been derived from the simulation tool based on first principles developed in this work.

Consequence modelling,vulnerability assessment and fuzzy fault tree analysis of hazardous storages in an industrial area

The hazards associated with major accident hazard (MAH) industries are fire, explosion and toxic gas releases. Of these, toxic gas release is the worst as it has the potential to cause extensive fatalities. Qualitative and quantitative hazard analyses are essential for the identitication and quantification of the hazards associated with chemical industries. This research work presents the results of a consequence analysis carried out to assess the damage potential of the hazardous material storages in an industrial area of central Kerala, India. A survey carried out in the major accident hazard (MAH) units in the industrial belt revealed that the major hazardous chemicals stored by the various industrial units are ammonia, chlorine, benzene, naphtha, cyclohexane, cyclohexanone and LPG. The damage potential of the above chemicals is assessed using consequence modelling. Modelling of pool fires for naphtha, cyclohexane, cyclohexanone, benzene and ammonia are carried out using TNO model. Vapor cloud explosion (VCE) modelling of LPG, cyclohexane and benzene are carried out using TNT equivalent model. Boiling liquid expanding vapor explosion (BLEVE) modelling of LPG is also carried out. Dispersion modelling of toxic chemicals like chlorine, ammonia and benzene is carried out using the ALOHA air quality model. Threat zones for different hazardous storages are estimated based on the consequence modelling. The distance covered by the threat zone was found to be maximum for chlorine release from a chlor-alkali industry located in the area. The results of consequence modelling are useful for the estimation of individual risk and societal risk in the above industrial area.Vulnerability assessment is carried out using probit functions for toxic, thermal and pressure loads. Individual and societal risks are also estimated at different locations. Mapping of threat zones due to different incident outcome cases from different MAH industries is done with the help of Are GIS.Fault Tree Analysis (FTA) is an established technique for hazard evaluation. This technique has the advantage of being both qualitative and quantitative, if the probabilities and frequencies of the basic events are known. However it is often difficult to estimate precisely the failure probability of the components due to insufficient data or vague characteristics of the basic event. It has been reported that availability of the failure probability data pertaining to local conditions is surprisingly limited in India. This thesis outlines the generation of failure probability values of the basic events that lead to the release of chlorine from the storage and filling facility of a major chlor-alkali industry located in the area using expert elicitation and proven fuzzy logic. Sensitivity analysis has been done to evaluate the percentage contribution of each basic event that could lead to chlorine release. Two dimensional fuzzy fault tree analysis (TDFFTA) has been proposed for balancing the hesitation factor invo1ved in expert elicitation .

Qualitative air flow modelling and analysis of data centre air conditioning as multiple jet array

This work identifies the importance of plenum pressure on the performance of the data centre. The present methodology followed in the industry considers the pressure drop across the tile as a dependant variable, but it is shown in this work that this is the only one independent variable that is responsible for the entire flow dynamics in the data centre, and any design or assessment procedure must consider the pressure difference across the tile as the primary independent variable. This concept is further explained by the studies on the effect of dampers on the flow characteristics. The dampers have found to introduce an additional pressure drop there by reducing the effective pressure drop across the tile. The effect of damper is to change the flow both in quantitative and qualitative aspects. But the effect of damper on the flow in the quantitative aspect is only considered while using the damper as an aid for capacity control. Results from the present study suggest that the use of dampers must be avoided in data centre and well designed tiles which give required flow rates must be used in the appropriate locations. In the present study the effect of hot air recirculation is studied with suitable assumptions. It identifies that, the pressure drop across the tile is a dominant parameter which governs the recirculation. The rack suction pressure of the hardware along with the pressure drop across the tile determines the point of recirculation in the cold aisle. The positioning of hardware in the racks play an important role in controlling the recirculation point. The present study is thus helpful in the design of data centre air flow, based on the theory of jets. The air flow can be modelled both quantitatively and qualitatively based on the results.

“Qualitative Air Flow Modelling And Analysis Of Data Centre Air Conditioning As Multiple Jet Array

In the present study the effect of hot air recirculation is studied with suitable assumptions. It identifies that, the pressure drop across the tile is a dominant parameter which governs the recirculation. The rack suction pressure of the hardware along with the pressure drop across the tile determines the point of recirculation in the cold aisle. The positioning of hardware in the racks play an important role in controlling the recirculation point. The present study is thus helpful in the design of data centre air flow, based on the theory of jets. The air flow can be modelled both quantitatively and qualitatively based on the results

Modelling of Ultraviolet and Vissible Emissions in Comets

Comets are the spectacular objects in the night sky since the dawn of mankind. Due to their giant apparitions and enigmatic behavior, followed by coincidental calamities, they were termed as notorious and called as `bad omens'. With a systematic study of these objects modern scienti c community understood that these objects are part of our solar system. Comets are believed to be remnant bodies of at the end of evolution of solar system and possess the material of solar nebula. Hence, these are considered as most pristine objects which can provide the information about the conditions of solar nebula. These are small bodies of our solar system, with a typical size of about a kilometer to a few tens of kilometers orbiting the Sun in highly elliptical orbits. The solid body of a comet is nucleus which is a conglomerated mixture of water ice, dust and some other gases. When the cometary nucleus advances towards the Sun in its orbit the ices sublimates and produces the gaseous envelope around the nucleus which is called coma. The gravity of cometary nucleus is very small and hence can not in uence the motion of gases in the cometary coma. Though the cometary nucleus is a few kilometers in size they can produce a transient, extensive, and expanding atmosphere with size several orders of magnitude larger in space. By ejecting gas and dust into space comets became the most active members of the solar system. The solar radiation and the solar wind in uences the motion of dust and ions and produces dust and ion tails, respectively. Comets have been observed in di erent spectral regions from rocket, ground and space borne optical instruments. The observed emission intensities are used to quantify the chemical abundances of di erent species in the comets. The study of various physical and chemical processes that govern these emissions is essential before estimating chemical abundances in the coma. Cameron band emission of CO molecule has been used to derive CO2 abundance in the comets based on the assumption that photodissociation of CO2 mainly produces these emissions. Similarly, the atomic oxygen visible emissions have been used to probe H2O in the cometary coma. The observed green ([OI] 5577 A) to red-doublet emission ([OI] 6300 and 6364 A) ratio has been used to con rm H2O as the parent species of these emissions. In this thesis a model is developed to understand the photochemistry of these emissions and applied to several comets. The model calculated emission intensities are compared with the observations done by space borne instruments like International Ultraviolet Explorer (IUE) and Hubble Space Telescope (HST) and also by various ground based telescopes.

Modification of Polypropylene/High Density Polyethylene Blend Using Nanokaolinite Clay and E-Glass Fibre: Preparation, Characterization and Micromechanical Modelling

Upgrading two widely used standard plastics, polypropylene (PP) and high density polyethylene (HDPE), and generating a variety of useful engineering materials based on these blends have been the main objective of this study. Upgradation was effected by using nanomodifiers and/or fibrous modifiers. PP and HDPE were selected for modification due to their attractive inherent properties and wide spectrum of use. Blending is the engineered method of producing new materials with tailor made properties. It has the advantages of both the materials. PP has high tensile and flexural strength and the HDPE acts as an impact modifier in the resultant blend. Hence an optimized blend of PP and HDPE was selected as the matrix material for upgradation. Nanokaolinite clay and E-glass fibre were chosen for modifying PP/HDPE blend. As the first stage of the work, the mechanical, thermal, morphological, rheological, dynamic mechanical and crystallization characteristics of the polymer nanocomposites prepared with PP/HDPE blend and different surface modified nanokaolinite clay were analyzed. As the second stage of the work, the effect of simultaneous inclusion of nanokaolinite clay (both N100A and N100) and short glass fibres are investigated. The presence of nanofiller has increased the properties of hybrid composites to a greater extent than micro composites. As the last stage, micromechanical modeling of both nano and hybrid A composite is carried out to analyze the behavior of the composite under load bearing conditions. These theoretical analyses indicate that the polymer-nanoclay interfacial characteristics partially converge to a state of perfect interfacial bonding (Takayanagi model) with an iso-stress (Reuss IROM) response. In the case of hybrid composites the experimental data follows the trend of Halpin-Tsai model. This implies that matrix and filler experience varying amount of strain and interfacial adhesion between filler and matrix and also between the two fillers which play a vital role in determining the modulus of the hybrid composites.A significant observation from this study is that the requirement of higher fibre loading for efficient reinforcement of polymers can be substantially reduced by the presence of nanofiller together with much lower fibre content in the composite. Hybrid composites with both nanokaolinite clay and micron sized E-glass fibre as reinforcements in PP/HDPE matrix will generate a novel class of high performance, cost effective engineering material.