Predicting Combinatorial Binding of Transcription Factors to Regulatory Elements in the Human Genome by Association Rule Mining

Cis-acting transcriptional regulatory elements in mammalian genomes typically contain specific combinations of binding sites for various transcription factors. Although some cisregulatory elements have been well studied, the combinations of transcription factors that regulate normal expression levels for the vast majority of the 20,000 genes in the human genome are unknown. We hypothesized that it should be possible to discover transcription factor combinations that regulate gene expression in concert by identifying over-represented combinations of sequence motifs that occur together in the genome. In order to detect combinations of transcription factor binding motifs, we developed a data mining approach based on the use of association rules, which are typically used in market basket analysis. We scored each segment of the genome for the presence or absence of each of 83 transcription factor binding motifs, then used association rule mining algorithms to mine this dataset, thus identifying frequently occurring pairs of distinct motifs within a segment. Results: Support for most pairs of transcription factor binding motifs was highly correlated across different chromosomes although pair significance varied. Known true positive motif pairs showed higher association rule support, confidence, and significance than background. Our subsets of high-confidence, high-significance mined pairs of transcription factors showed enrichment for co-citation in PubMed abstracts relative to all pairs, and the predicted associations were often readily verifiable in the literature. Conclusion: Functional elements in the genome where transcription factors bind to regulate expression in a combinatorial manner are more likely to be predicted by identifying statistically and biologically significant combinations of transcription factor binding motifs than by simply scanning the genome for the occurrence of binding sites for a single transcription factor.NIAAA Alcohol Training GrantNational Science FoundationCellular and Molecular Biolog

Association Analysis Techniques for Discovering Functional Modules from Microarray Data

An application of great interest in microarray data analysis is the identification of a group of genes that show very similar patterns of expression in a data set, and are expected to represent groups of genes that perform common/similar functions, also known as functional modules. Although clustering offers a natural solution to this problem, it suffers from the limitation that it uses all the conditions to compare two genes, whereas only a subset of them may be relevant. Association analysis offers an alternative route for finding such groups of genes that may be co-expressed only over a subset of the experimental conditions used to prepare the data set. The techniques in this field attempt to find groups of data objects that contain coherent values across a set of attributes, in an exhaustive and efficient manner. In this paper, we illustrate how a generalization of the techniques in association analysis for real-valued data can be utilized to extract coherent functional modules from large microarray data sets

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

A graph-based representation of Gene Expression profiles in DNA microarrays

This paper proposes a new and very flexible data model, called gene expression graph (GEG), for genes expression analysis and classification. Three features differentiate GEGs from other available microarray data representation structures: (i) the memory occupation of a GEG is independent of the number of samples used to built it; (ii) a GEG more clearly expresses relationships among expressed and non expressed genes in both healthy and diseased tissues experiments; (iii) GEGs allow to easily implement very efficient classifiers. The paper also presents a simple classifier for sample-based classification to show the flexibility and user-friendliness of the proposed data structur

Using open access literature to guide full-text query formulation

*Background*
Much scientific knowledge is contained in the details of the full-text biomedical literature. Most research in automated retrieval presupposes that the target literature can be downloaded and preprocessed prior to query. Unfortunately, this is not a practical or maintainable option for most users due to licensing restrictions, website terms of use, and sheer volume. Scientific article full-text is increasingly queriable through portals such as PubMed Central, Highwire Press, Scirus, and Google Scholar. However, because these portals only support very basic Boolean queries and full text is so expressive, formulating an effective query is a difficult task for users. We propose improving the formulation of full-text queries by using the open access literature as a proxy for the literature to be searched. We evaluated the feasibility of this approach by building a high-precision query for identifying studies that perform gene expression microarray experiments.

*Methodology and Results*
We built decision rules from unigram and bigram features of the open access literature. Minor syntax modifications were needed to translate the decision rules into the query languages of PubMed Central, Highwire Press, and Google Scholar. We mapped all retrieval results to PubMed identifiers and considered our query results as the union of retrieved articles across all portals. Compared to our reference standard, the derived full-text query found 56% (95% confidence interval, 52% to 61%) of intended studies, and 90% (86% to 93%) of studies identified by the full-text search met the reference standard criteria. Due to this relatively high precision, the derived query was better suited to the intended application than alternative baseline MeSH queries.

*Significance*
Using open access literature to develop queries for full-text portals is an open, flexible, and effective method for retrieval of biomedical literature articles based on article full-text. We hope our approach will raise awareness of the constraints and opportunities in mainstream full-text information retrieval and provide a useful tool for today’s researchers.
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Using open access literature to guide full-text query formulation

*Background* 
Much scientific knowledge is contained in the details of the full-text biomedical literature. Most research in automated retrieval presupposes that the target literature can be downloaded and preprocessed prior to query. Unfortunately, this is not a practical or maintainable option for most users due to licensing restrictions, website terms of use, and sheer volume. Scientific article full-text is increasingly queriable through portals such as PubMed Central, Highwire Press, Scirus, and Google Scholar. However, because these portals only support very basic Boolean queries and full text is so expressive, formulating an effective query is a difficult task for users. We propose improving the formulation of full-text queries by using the open access literature as a proxy for the literature to be searched. We evaluated the feasibility of this approach by building a high-precision query for identifying studies that perform gene expression microarray experiments.
 
*Methodology and Results* 
We built decision rules from unigram and bigram features of the open access literature. Minor syntax modifications were needed to translate the decision rules into the query languages of PubMed Central, Highwire Press, and Google Scholar. We mapped all retrieval results to PubMed identifiers and considered our query results as the union of retrieved articles across all portals. Compared to our reference standard, the derived full-text query found 56% (95% confidence interval, 52% to 61%) of intended studies, and 90% (86% to 93%) of studies identified by the full-text search met the reference standard criteria. Due to this relatively high precision, the derived query was better suited to the intended application than alternative baseline MeSH queries.
 
*Significance* 
Using open access literature to develop queries for full-text portals is an open, flexible, and effective method for retrieval of biomedical literature articles based on article full-text. We hope our approach will raise awareness of the constraints and opportunities in mainstream full-text information retrieval and provide a useful tool for today’s researchers.
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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

Differential gene expression graphs: A data structure for classification in DNA microarrays

This paper proposes an innovative data structure to be used as a backbone in designing microarray phenotype sample classifiers. The data structure is based on graphs and it is built from a differential analysis of the expression levels of healthy and diseased tissue samples in a microarray dataset. The proposed data structure is built in such a way that, by construction, it shows a number of properties that are perfectly suited to address several problems like feature extraction, clustering, and classificatio

Gene expression classifiers and out-of-class samples detection

The proper application of statistics, machine learning, and data-mining techniques in routine clinical diagnostics to classify diseases using their genetic expression profile is still a challenge. One critical issue is the overall inability of most state-of-the-art classifiers to identify out-of-class samples, i.e., samples that do not belong to any of the available classes. This paper shows a possible explanation for this problem and suggests how, by analyzing the distribution of the class probability estimates generated by a classifier, it is possible to build decision rules able to significantly improve its performance