3255925
A data mining method to predict transcriptional regulatory sites based on differentially expressed genes in human genome
Very large-scale gene expression analysis, i.e., UniGene and dbEST, are provided to find those genes with significantly differential expression in specific tissues. The differentially expressed genes in a specific tissue are potentially regulated concurrently by a combination of transcription factors. This study attempts to mine putative binding sites on how combinations of the known regulatory sites homologs and over-represented repetitive elements are distributed in the promoter regions of considered groups of differentially expressed genes. We propose a data mining approach to statistically discover the significantly tissue-specific combinations of known site homologs and over-represented repetitive sequences, which are distributed in the promoter regions of differential gene groups. The association rules mined would facilitate to predict putative regulatory elements and identify genes potentially co-regulated by the putative regulatory elements.
17764116
Identifying transcriptional regulatory sites in the human genome using an integrated computation
Recently, biological databases and analytical methods have become available for analyzing gene expression and transcriptional regulatory sequences. However, users must make the complicated analyses to query the data in various databases, and to analyze the gene upstreams using various predictive tools. Beyond methods for predicting transcriptional regulatory sites, new automated and integrated methods for analyzing gene upstream sequences on a higher level are urgently required. We present an integrated system to predict transcriptional regulatory sites and detect co-occurrence of these regulatory sites after a set of genes are input. The system comprises a biological data warehousing system, pattern discovery programs, pattern occurrence association detectors and user interfaces. User profiles and history pages enable users to trace the sequence analyses for transcriptional regulatory sites.
1404678
SpliceInfo: an information repository for mRNA alternative splicing in human genome
We have developed an information repository named SpliceInfo to collect the occurrences of the four major alternative-splicing (AS) modes in human genome; these include exon skipping, 5′-alternative splicing, 3′-alternative splicing and intron retention. The dataset is derived by comparing the nucleotide and protein sequences available for a given gene for evidence of AS. Additional features such as the tissue specificity of the mRNA, the protein domain contained by exons, the GC-ratio of exons, the repeats contained within the exons, and the Gene Ontology are annotated computationally for each exonic region that is alternatively spliced. Motivated by a previous investigation of AS-related motifs such as exonic splicing enhancer and exonic splicing silencer, this resource also provides a means of identifying motifs candidates and this should help to identify potential regulatory mechanisms within a particular exonic sequence set and its two flanking intronic sequence sets. This is carried out using motif discovery tools to identify motif candidates related to alternative splicing regulation and together with a secondary structure prediction tool, will help in the identification of the structural properties of such regulatory motifs. The integrated resource is now available on http://SpliceInfo.mbc.NCTU.edu.tw/.
31128018
The Repetitive Sequence Database and Mining Putative Regulatory Elements in Gene Promoter Regions
At least 43% of the human genome is occupied by repetitive elements. Moreover, around 51% of the rice genome is occupied by repetitive elements. The analysis of repetitive elements reveals that repetitive elements in our genome may have been very important in the evolutionary genomics. The first part of this study is to describe a database of repetitive elements - RSDB. The RSDB database contains repetitive elements, which are classified into the following categories: exact, tandem, and similar. The interfaces needed to query and show the results and statistical data, such as the relationship between repetitive elements and genes, cross-references of repetitive elements among different organisms, and so on, are provided. The second part of this study then attempts to mine the putative binding site for information on how combinations of the known regulatory sites and overrepresented repetitive elements in RSDB are distributed in the promoter regions of groups of functionally related genes. The overrepresented repetitive elements appearing in the associations are possible transcription factor binding sites. Our proposed approach is applied to Saccharomyces cerevisiae and the promoter regions of Yeast ORFs. The complete contents of RSDB and partial putative binding sites are available to the public at www.rsdb.csie.ncu.edu.tw. The readers may download partial query results.
7391844
Database of repetitive elements in complete genomes and data mining using transcription factor binding sites
Approximately 43% of the human genome is occupied by repetitive elements. Even more, around 51% of the rice genome is occupied by repetitive elements. The analysis presented here indicates that repetitive elements in complete genomes may have been very important in the evolutionary genomics. In this study, a database, called the Repeat Sequence Database, is first designed and implemented to store complete and comprehensive repetitive sequences. See http://rsdb.csie.ncu.edu.tw for more information. The database contains direct, inverted and palindromic repetitive sequences, and each repetitive sequence has a variable length ranging from seven to many hundred nucleotides. The repetitive sequences in the database are explored using a mathematical algorithm to mine rules on how combinations of individual binding sites are distributed among repetitive sequences in the database. Combinations of transcription factor binding sites in the repetitive sequences are obtained and then data mining techniques are applied to mine association rules from these combinations. The discovered associations are further pruned to remove insignificant associations and obtain a set of associations. The mined association rules facilitate efforts to identify gene classes regulated by similar mechanisms and accurately predict regulatory elements. Experiments are performed on several genomes including C. elegans, human chromosome 22, and yeast.
6014802
Identifying the combination of genetic factors that determine susceptibility to cervical cancer
Cervical cancer is common among women all over the world. Although infection with high-risk types of human papillomavirus (HPV) has been identified as the primary cause of cervical cancer, only some of those infected go on to develop cervical cancer. Obviously, the progression from HPV infection to cancer involves other environmental and host factors. Recent population-based twin and family studies have demonstrated the importance of the hereditary component of cervical cancer, associated with genetic susceptibility. Consequently, single-nucleotide polymorphism (SNP) markers and microsatellites should be considered genetic factors for determining what combinations of genetic factors are involved in precancerous changes to cervical cancer. This study employs a Bayesian network and four different decision tree algorithms, and compares the performance of these learning algorithms. The results of this study raise the possibility of investigations that could identify combinations of genetic factors, such as SNPs and microsatellites, that influence the risk associated with common complex multifactorial diseases, such as cervical cancer. The web site associated with this study is http://140.115.155.8/FactorAnalysis/.
2900872
Analysis of differentially-regulated genes within a regulatory network by GPS genome navigation
MOTIVATION
A critical challenge of the post-genomic era is to understand how genes are differentially regulated even when they belong to a given network. Because the fundamental mechanism controlling gene expression operates at the level of transcription initiation, computational techniques have been developed that identify cis regulatory features and map such features into expression patterns to classify genes into distinct networks. However, these methods are not focused on distinguishing between differentially regulated genes within a given network. Here we describe an unsupervised machine learning method, termed GPS for gene promoter scan, that discriminates among co-regulated promoters by simultaneously considering both cis-acting regulatory features and gene expression. GPS is particularly useful for knowledge discovery in environments with reduced datasets and high levels of uncertainty.


RESULTS
Application of this method to the enteric bacteria Escherichia coli and Salmonella enterica uncovered novel members, as well as regulatory interactions in the regulon controlled by the PhoP protein that were not discovered using previous approaches. The predictions made by GPS were experimentally validated to establish that the PhoP protein uses multiple mechanisms to control gene transcription, and is a central element in a highly connected network.


AVAILABILITY
The scripts and programs used in this work are accessible from the gps-tools.wustl.edu website. Data and predictions are available by request.
7951451
A New Test System for Stability Measurement of Marker Gene Selection in DNA Microarray Data Analysis
Microarray gene expression data contains informative features that reflect the critical processes controlling prominent biological functions. Feature selection algorithms have been used in previous biomedical research to find the “marker” genes whose expression value change corresponds to the most eminent difference between specimen classes. One problem encountered in such analysis is the imbalance between very large numbers of genes versus relatively fewer specimen samples. A common concern, therefore, is “overfitting” the data and deriving a set of marker genes with low stability over the entire set of possible specimens. To address this problem, we propose a new test environment in which synthetic data is perturbed to simulate possible variations in gene expression values. The goal is for the generated data to have appropriate properties that match natural data, and that are appropriate for use in testing the sensitivity of feature selection algorithms and validating the robustness of selected marker genes. In this paper, we evaluate a statistically-based resampling approach and a Principal Components Analysis (PCA)-based linear noise distribution approach. Our results show that both methods generate reasonable synthetic data and that the signal/noise rate (with variation weights at 5%, 10%, 20% and 30%) measurably impacts the classification accuracy and the marker genes selected. Based on these results, we identify the most appropriate marker gene selection and classification techniques for each type and level of noise we modeled.
5664354
Association analysis with one scan of databases
Mining frequent patterns with an FP-tree avoids costly candidate generation and repeatedly occurrence frequency checking against the support threshold. It therefore achieves better performance and efficiency than Apriori-like algorithms. However the database still needs to be scanned twice to get the FP-tree. This can be very time-consuming when new data are added to an existing database because two scans may be needed for not only the new data but also the existing data. This paper presents a new data structure P-tree, Pattern Tree, and a new technique, which can get the P-tree through only one scan of the database and can obtain the corresponding FP-tree with a specified support threshold. Updating a P-tree with new data needs one scan of the new data only, and the existing data do not need to be re-scanned.
35266077
VQ-Based Gray Watermark Hiding Scheme and Genetic Index Assignment
A vector quantisation (VQ) based watermarking scheme for hiding the gray watermark is presented. It expands the watermark size, and employs VQ index assignment procedure with genetic algorithm, called genetic index assignment (GIA), for watermarking. The gray watermark is coded by VQ, and obtained indices are translated into a binary bitstream with a much smaller size. We partition the codebook into two sub-codebooks, and use either one of them based on the value of the bit for embedding. Next, GIA is employed to find better imperceptibility of watermarked image. Experimental results show that the proposed method possesses advantages over other related methods in literature.
10859494
Adaptive watermarking using relationships between wavelet coefficients
We propose an approach that hides watermarks in relationships between wavelet coefficients. This approach minimizes the perceptual distortion of watermarked images, measured by PSNR or just noticeable distortion (JND). Therefore, the strength of watermarks can be enlarged to increase the robustness of the watermarks, while keeping the quality of watermarked images visually acceptable. Experimental results show that the watermark is still detectable after common image processing operations such as JPEG compression, Gaussian filtering and sharpening.