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.
5048088
KinasePhos: a web tool for identifying protein kinase-specific phosphorylation sites
KinasePhos is a novel web server for computationally identifying catalytic kinase-specific phosphorylation sites. The known phosphorylation sites from public domain data sources are categorized by their annotated protein kinases. Based on the profile hidden Markov model, computational models are learned from the kinase-specific groups of the phosphorylation sites. After evaluating the learned models, the model with highest accuracy was selected from each kinase-specific group, for use in a web-based prediction tool for identifying protein phosphorylation sites. Therefore, this work developed a kinase-specific phosphorylation site prediction tool with both high sensitivity and specificity. The prediction tool is freely available at .
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/.
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/.
18861193
An agent-based system to discover protein-protein interactions, identify protein complexes and proteins with multiple peptide mass fingerprints
Proteins "work together" by actually binding to form multicomponent complexes that carry out specific functions. Proteomic analyses based on the mass spectrum are now key methods to determine the components in protein complexes. The protein-protein interaction or functional association may be known to exist among the extracted protein spots while analyzing the proteins on the 2D gel. In this study, we develop an agent-based system, namely AgentMultiProtIdent, which integrated two protein identification tools and a variety of databases storing relations among proteins and used to discover protein-protein interactions and protein functional associations, and identify protein complexes and proteins with multiple peptide mass fingerprints as input. The system takes Multiple Peptide Mass Fingerprints (PMFs) as a whole in the protein complex or protein identification. With the relations among proteins, it may greatly improve the accuracy of identification of protein complexes. Also, possible relationship of the multiple peptide mass fingerprints, such as ontology relation, can be discovered by our system, especially in the identification of protein complexes. The agent-based system is now available on the Web at http://dbms104.csie.ncu.edu.tw/ approximately protein/NEW2/.
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.
18362184
Toward a Universal Platform for Integrating Embodied Conversational Agent Components
Embodied Conversational Agents (ECAs) are computer generated life-like characters that interact with human users in face-to-face conversations. To achieve natural multi-modal conversations, ECA systems are very sophisticated and require many building assemblies and thus are difficult for individual research groups to develop. This paper proposes a generic architecture, the Universal ECA Framework, which is currently under development and includes a blackboard-based platform, a high-level protocol to integrate general purpose ECA components and ease ECA system prototyping.
12579085
The super laceability of the hypercubes
A k-container C(u,v) of a graph G is a set of k disjoint paths joining u to v. A k-container C(u, v) is a k*-container if every vertex of G is incident with a path in C(u,v). A bipartite graph G is k*-laceable if there exists a k*-container between any two vertices u, v from different partite set of G. A bipartite graph G with connectivity k is super laceable if it is i*-laceable for all i ≤ k. A bipartite graph G with connectivity k is f-edge fault-tolerant super laceable if G - F is i*-laceable for any 1 ≤ i ≤ k-f and for any edge subset F with |F|=f r is super laceable. Moreover, Q r is f-edge fault-tolerant super laceable for any f ≤ r - 2.
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.
3641866
The iProClass integrated database for protein functional analysis
Increasingly, scientists have begun to tackle gene functions and other complex regulatory processes by studying organisms at the global scales for various levels of biological organization, ranging from genomes to metabolomes and physiomes. Meanwhile, new bioinformatics methods have been developed for inferring protein function using associative analysis of functional properties to complement the traditional sequence homology-based methods. To fully exploit the value of the high-throughput system biology data and to facilitate protein functional studies requires bioinformatics infrastructures that support both data integration and associative analysis. The iProClass database, designed to serve as a framework for data integration in a distributed networking environment, provides comprehensive descriptions of all proteins, with rich links to over 50 databases of protein family, function, pathway, interaction, modification, structure, genome, ontology, literature, and taxonomy. In particular, the database is organized with PIRSF family classification and maps to other family, function, and structure classification schemes. Coupled with the underlying taxonomic information for complete genomes, the iProClass system (http://pir.georgetown.edu/iproclass/) supports associative studies of protein family, domain, function, and structure. A case study of the phosphoglycerate mutases illustrates a systematic approach for protein family and phylogenetic analysis. Such studies may serve as a basis for further analysis of protein functional evolution, and its relationship to the co-evolution of metabolic pathways, cellular networks, and organisms.