Expression cartography of human tissues using self organizing maps

Background: The availability of parallel, high-throughput microarray and sequencing experiments poses a challenge how to best arrange and to analyze the obtained heap of multidimensional data in a concerted way. Self organizing maps (SOM), a machine learning method, enables the parallel sample- and gene-centered view on the data combined with strong visualization and second-level analysis capabilities. The paper addresses aspects of the method with practical impact in the context of expression analysis of complex data sets.
Results: The method was applied to generate a SOM characterizing the whole genome expression profiles of 67 healthy human tissues selected from ten tissue categories (adipose, endocrine, homeostasis, digestion, exocrine, epithelium, sexual reproduction, muscle, immune system and nervous tissues). SOM mapping reduces the dimension of expression data from ten thousands of genes to a few thousands of metagenes where each metagene acts as representative of a minicluster of co-regulated single genes. Tissue-specific and common properties shared between groups of tissues emerge as a handful of localized spots in the tissue maps collecting groups of co-regulated and co-expressed metagenes. The functional context of the spots was discovered using overrepresentation analysis with respect to pre-defined gene sets of known functional impact. We found that tissue related spots typically contain enriched populations of gene sets well corresponding to molecular processes in the respective tissues. Analysis techniques normally used at the gene-level such as two-way hierarchical clustering provide a better signal-to-noise ratio and a better representativeness of the method if applied to the metagenes. Metagene-based clustering analyses aggregate the tissues into essentially three clusters containing nervous, immune system and the remaining tissues. 
Conclusions: The global view on the behavior of a few well-defined modules of correlated and differentially expressed genes is more intuitive and more informative than the separate discovery of the expression levels of hundreds or thousands of individual genes. The metagene approach is less sensitive to a priori selection of genes. It can detect a coordinated expression pattern whose components would not pass single-gene significance thresholds and it is able to extract context-dependent patterns of gene expression in complex data sets.
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Expression cartography of human tissues using self organizing maps

Background: The availability of parallel, high-throughput microarray and sequencing experiments poses a challenge how to best arrange and to analyze the obtained heap of multidimensional data in a concerted way. Self organizing maps (SOM), a machine learning method, enables the parallel sample- and gene-centered view on the data combined with strong visualization and second-level analysis capabilities. The paper addresses aspects of the method with practical impact in the context of expression analysis of complex data sets.
Results: The method was applied to generate a SOM characterizing the whole genome expression profiles of 67 healthy human tissues selected from ten tissue categories (adipose, endocrine, homeostasis, digestion, exocrine, epithelium, sexual reproduction, muscle, immune system and nervous tissues). SOM mapping reduces the dimension of expression data from ten thousands of genes to a few thousands of metagenes where each metagene acts as representative of a minicluster of co-regulated single genes. Tissue-specific and common properties shared between groups of tissues emerge as a handful of localized spots in the tissue maps collecting groups of co-regulated and co-expressed metagenes. The functional context of the spots was discovered using overrepresentation analysis with respect to pre-defined gene sets of known functional impact. We found that tissue related spots typically contain enriched populations of gene sets well corresponding to molecular processes in the respective tissues. Analysis techniques normally used at the gene-level such as two-way hierarchical clustering provide a better signal-to-noise ratio and a better representativeness of the method if applied to the metagenes. Metagene-based clustering analyses aggregate the tissues into essentially three clusters containing nervous, immune system and the remaining tissues. 
Conclusions: The global view on the behavior of a few well-defined modules of correlated and differentially expressed genes is more intuitive and more informative than the separate discovery of the expression levels of hundreds or thousands of individual genes. The metagene approach is less sensitive to a priori selection of genes. It can detect a coordinated expression pattern whose components would not pass single-gene significance thresholds and it is able to extract context-dependent patterns of gene expression in complex data sets.
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An Overview of the Use of Neural Networks for Data Mining Tasks

In the recent years the area of data mining has experienced a considerable demand for technologies that extract knowledge from large and complex data sources. There is a substantial commercial interest as well as research investigations in the area that aim to develop new and improved approaches for extracting information, relationships, and patterns from datasets. Artificial Neural Networks (NN) are popular biologically inspired intelligent methodologies, whose classification, prediction and pattern recognition capabilities have been utilised successfully in many areas, including science, engineering, medicine, business, banking, telecommunication, and many other fields. This paper highlights from a data mining perspective the implementation of NN, using supervised and unsupervised learning, for pattern recognition, classification, prediction and cluster analysis, and focuses the discussion on their usage in bioinformatics and financial data analysis tasks

Context-aware visual exploration of molecular databases

Facilitating the visual exploration of scientific data has received increasing attention in the past decade or so. Especially in life science related application areas the amount of available data has grown at a breath taking pace. In this paper we describe an approach that allows for visual inspection of large collections of molecular compounds. In contrast to classical visualizations of such spaces we incorporate a specific focus of analysis, for example the outcome of a biological experiment such as high throughout screening results. The presented method uses this experimental data to select molecular fragments of the underlying molecules that have interesting properties and uses the resulting space to generate a two dimensional map based on a singular value decomposition algorithm and a self organizing map. Experiments on real datasets show that the resulting visual landscape groups molecules of similar chemical properties in densely connected regions

Fast training of self organizing maps for the visual exploration of molecular compounds

Visual exploration of scientific data in life science area is a growing research field due to the large amount of available data. The Kohonen’s Self Organizing Map (SOM) is a widely used tool for visualization of multidimensional data. In this paper we present a fast learning algorithm for SOMs that uses a simulated annealing method to adapt the learning parameters. The algorithm has been adopted in a data analysis framework for the generation of similarity maps. Such maps provide an effective tool for the visual exploration of large and multi-dimensional input spaces. The approach has been applied to data generated during the High Throughput Screening of molecular compounds; the generated maps allow a visual exploration of molecules with similar topological properties. The experimental analysis on real world data from the National Cancer Institute shows the speed up of the proposed SOM training process in comparison to a traditional approach. The resulting visual landscape groups molecules with similar chemical properties in densely connected regions

Probabilistic estimation of microarray data reliability and underlying gene expression

Background: The availability of high throughput methods for measurement of mRNA concentrations makes the reliability of conclusions drawn from the data and global quality control of samples and hybridization important issues. We address these issues by an information theoretic approach, applied to discretized expression values in replicated gene expression data. Results: Our approach yields a quantitative measure of two important parameter classes: First, the probability $P(\sigma | S)$ that a gene is in the biological state $\sigma$ in a certain variety, given its observed expression $S$ in the samples of that variety. Second, sample specific error probabilities which serve as consistency indicators of the measured samples of each variety. The method and its limitations are tested on gene expression data for developing murine B-cells and a $t$-test is used as reference. On a set of known genes it performs better than the $t$-test despite the crude discretization into only two expression levels. The consistency indicators, i.e. the error probabilities, correlate well with variations in the biological material and thus prove efficient. Conclusions: The proposed method is effective in determining differential gene expression and sample reliability in replicated microarray data. Already at two discrete expression levels in each sample, it gives a good explanation of the data and is comparable to standard techniques.Comment: 11 pages, 4 figure

Preparation and characterization of magnetite (Fe3O4) nanoparticles By Sol-Gel method

The magnetite (Fe3O4) nanoparticles were successfully synthesized and annealed under vacuum at different temperature. The Fe3O4 nanoparticles prepared via sol-gel assisted method and annealed at 200-400ºC were characterized by Fourier Transformation Infrared Spectroscopy (FTIR), X-ray Diffraction spectra (XRD), Field Emission Scanning Electron Microscope (FESEM) and Atomic Force Microscopy (AFM). The XRD result indicate the presence of Fe3O4 nanoparticles, and the Scherer`s Formula calculated the mean particles size in range of 2-25 nm. The FESEM result shows that the morphologies of the particles annealed at 400ºC are more spherical and partially agglomerated, while the EDS result indicates the presence of Fe3O4 by showing Fe-O group of elements. AFM analyzed the 3D and roughness of the sample; the Fe3O4 nanoparticles have a minimum diameter of 79.04 nm, which is in agreement with FESEM result. In many cases, the synthesis of Fe3O4 nanoparticles using FeCl3 and FeCl2 has not been achieved, according to some literatures, but this research was able to obtained Fe3O4 nanoparticles base on the characterization results

Mining SOM expression portraits: Feature selection and integrating concepts of molecular function

Background: 
Self organizing maps (SOM) enable the straightforward portraying of high-dimensional data of large sample collections in terms of sample-specific images. The analysis of their texture provides so-called spot-clusters of co-expressed genes which require subsequent significance filtering and functional interpretation. We address feature selection in terms of the gene ranking problem and the interpretation of the obtained spot-related lists using concepts of molecular function.

Results: 
Different expression scores based either on simple fold change-measures or on regularized Students t-statistics are applied to spot-related gene lists and compared with special emphasis on the error characteristics of microarray expression data. The spot-clusters are analyzed using different methods of gene set enrichment analysis with the focus on overexpression and/or overrepresentation of predefined sets of genes. Metagene-related overrepresentation of selected gene sets was mapped into the SOM images to assign gene function to different regions. Alternatively we estimated set-related overexpression profiles over all samples studied using a gene set enrichment score. It was also applied to the spot-clusters to generate lists of enriched gene sets. We used the tissue body index data set, a collection of expression data of human tissues, as an illustrative example. We found that tissue related spots typically contain enriched populations of gene sets well corresponding to molecular processes in the respective tissues. In addition, we display special sets of housekeeping and of consistently weak and highly expressed genes using SOM data filtering. 

Conclusions:
The presented methods allow the comprehensive downstream analysis of SOM-transformed expression data in terms of cluster-related gene lists and enriched gene sets for functional interpretation. SOM clustering implies the ability to define either new gene sets using selected SOM spots or to verify and/or to amend existing ones

Adaptive Double Self-Organizing Map for Clustering Gene Expression Data

This thesis presents a novel clustering technique known as adaptive double self- organizing map (ADSOM) that addresses the issue of identifying the correct number of clusters. ADSOM has a flexible topology and performs clustering and cluster visualization simultaneously, thereby requiring no a priori knowledge about the number of clusters. ADSOM combines features of the popular self-organizing map with two- dimensional position vectors, which serve as a visualization tool to decide the number of clusters. It updates its free parameters during training and it allows convergence of its position vectors to a fairly consistent number of clusters provided that its initial number of nodes is greater than the expected number of clusters. A novel index is introduced based on hierarchical clustering of the final locations of position vectors. The index allows automated detection of the number of clusters, thereby reducing human error that could be incurred from counting clusters visually. The reliance of ADSOM in identifying the number of clusters is proven by applying it to publicly available gene expression data from multiple biological systems such as yeast, human, mouse, and bacteria