19643173
Modular organization of protein interaction networks
MOTIVATION
Accumulating evidence suggests that biological systems are composed of interacting, separable, functional modules. Identifying these modules is essential to understand the organization of biological systems.


RESULT
In this paper, we present a framework to identify modules within biological networks. In this approach, the concept of degree is extended from the single vertex to the sub-graph, and a formal definition of module in a network is used. A new agglomerative algorithm was developed to identify modules from the network by combining the new module definition with the relative edge order generated by the Girvan-Newman (G-N) algorithm. A JAVA program, MoNet, was developed to implement the algorithm. Applying MoNet to the yeast core protein interaction network from the database of interacting proteins (DIP) identified 86 simple modules with sizes larger than three proteins. The modules obtained are significantly enriched in proteins with related biological process Gene Ontology terms. A comparison between the MoNet modules and modules defined by Radicchi et al. (2004) indicates that MoNet modules show stronger co-clustering of related genes and are more robust to ties in betweenness values. Further, the MoNet output retains the adjacent relationships between modules and allows the construction of an interaction web of modules providing insight regarding the relationships between different functional modules. Thus, MoNet provides an objective approach to understand the organization and interactions of biological processes in cellular systems.


AVAILABILITY
MoNet is available upon request from the authors.
14219803
A new method to measure the semantic similarity of GO terms
MOTIVATION
Although controlled biochemical or biological vocabularies, such as Gene Ontology (GO) (http://www.geneontology.org), address the need for consistent descriptions of genes in different data sources, there is still no effective method to determine the functional similarities of genes based on gene annotation information from heterogeneous data sources.


RESULTS
To address this critical need, we proposed a novel method to encode a GO term's semantics (biological meanings) into a numeric value by aggregating the semantic contributions of their ancestor terms (including this specific term) in the GO graph and, in turn, designed an algorithm to measure the semantic similarity of GO terms. Based on the semantic similarities of GO terms used for gene annotation, we designed a new algorithm to measure the functional similarity of genes. The results of using our algorithm to measure the functional similarities of genes in pathways retrieved from the saccharomyces genome database (SGD), and the outcomes of clustering these genes based on the similarity values obtained by our algorithm are shown to be consistent with human perspectives. Furthermore, we developed a set of online tools for gene similarity measurement and knowledge discovery.


AVAILABILITY
The online tools are available at: http://bioinformatics.clemson.edu/G-SESAME.


SUPPLEMENTARY INFORMATION
http://bioinformatics.clemson.edu/Publication/Supplement/gsp.htm.
2887282
Rat Genome Database (RGD): mapping disease onto the genome
The Rat Genome Database (RGD, http://rgd.mcw.edu) is an NIH-funded project whose stated mission is 'to collect, consolidate and integrate data generated from ongoing rat genetic and genomic research efforts and make these data widely available to the scientific community'. In a collaboration between the Bioinformatics Research Center at the Medical College of Wisconsin, the Jackson Laboratory and the National Center for Biotechnology Information, RGD has been created to meet these stated aims. The rat is uniquely suited to its role as a model of human disease and the primary focus of RGD is to aid researchers in their study of the rat and in applying their results to studies in a wider context. In support of this we have integrated a large amount of rat genetic and genomic resources in RGD and these are constantly being expanded through ongoing literature and bulk dataset curation. RGD version 2.0, released in June 2001, includes curated data on rat genes, quantitative trait loci (QTL), microsatellite markers and rat strains used in genetic and genomic research. VCMap, a dynamic sequence-based homology tool was introduced, and allows researchers of rat, mouse and human to view mapped genes and sequences and their locations in the other two organisms, an essential tool for comparative genomics. In addition, RGD provides tools for gene prediction, radiation hybrid mapping, polymorphic marker selection and more. Future developments will include the introduction of disease-based curation expanding the curated information to cover popular disease systems studied in the rat. This will be integrated with the emerging rat genomic sequence and annotation pipelines to provide a high-quality disease-centric resource, applicable to human and mouse via comparative tools such as VCMap. RGD has a defined community outreach focus with a Visiting Scientist program and the Rat Community Forum, a web-based forum for rat researchers and others interested in using the rat as an experimental model. Thus, RGD is not only a valuable resource for those working with the rat but also for researchers in other model organisms wishing to harness the existing genetic and physiological data available in the rat to complement their own work.
8408042
The Rat Genome Database (RGD): developments towards a phenome database
The Rat Genome Database (RGD) (http://rgd.mcw.edu) aims to meet the needs of its community by providing genetic and genomic infrastructure while also annotating the strengths of rat research: biochemistry, nutrition, pharmacology and physiology. Here, we report on RGD's development towards creating a phenome database. Recent developments can be categorized into three groups. (i) Improved data collection and integration to match increased volume and biological scope of research. (ii) Knowledge representation augmented by the implementation of a new ontology and annotation system. (iii) The addition of quantitative trait loci data, from rat, mouse and human to our advanced comparative genomics tools, as well as the creation of new, and enhancement of existing, tools to enable users to efficiently browse and survey research data. The emphasis is on helping researchers find genes responsible for disease through the use of rat models. These improvements, combined with the genomic sequence of the rat, have led to a successful year at RGD with over two million page accesses that represent an over 4-fold increase in a year. Future plans call for increased annotation of biological information on the rat elucidated through its use as a model for human pathobiology. The continued development of toolsets will facilitate integration of these data into the context of rat genomic sequence, as well as allow comparisons of biological and genomic data with the human genomic sequence and of an increasing number of organisms.
6671949
Identification of critical genes in microarray experiments by a Neuro-Fuzzy approach
Gene expression profiling by microarray technology is usually difficult to interpret into a simpler pattern. One approach to resolve the complexity of gene expression profiles is the application of artificial neural networks (ANNs). A potential difficulty in this strategy, however, is that the non-linear nature of ANN makes it essentially a 'black-box' computation process. Addition of a fuzzy logic approach is useful because it can complement ANN by explicitly specifying membership function during computation. We employed a hybrid approach of neural network and fuzzy logic to further analyze a published microarray study of gene responses to eight bacteria in human macrophages. The original analysis by hierarchical clustering found common gene responses to all bacteria but did not address individual responses. Our method allowed exploration of the gene response of the host to individual bacterium. We implemented a two-layer, feed-forward neural network containing the principle of 'competitive learning' (i.e. 'winner-take-all'). The weights of the trained neural network were fed into a fuzzy logic inference system. A new measurement, called the impact rating (IR) was also introduced to explore the degree of importance of each gene. To assess the reliability of the IR value, a bootstrap re-sampling method was applied to the dataset and a confidence level for each IR was obtained. Our approach has successfully uncovered the unique features of host response to individual bacterium. Further, application of gene ontology (GO) annotation to the genes of high IR values in each response has suggested new biological pathways for individual host-pathogen interactions.
6056437
WormBase: a comprehensive data resource for Caenorhabditis biology and genomics
WormBase (http://www.wormbase.org), the model organism database for information about Caenorhabditis elegans and related nematodes, continues to expand in breadth and depth. Over the past year, WormBase has added multiple large-scale datasets including SAGE, interactome, 3D protein structure datasets and NCBI KOGs. To accommodate this growth, the International WormBase Consortium has improved the user interface by adding new features to aid in navigation, visualization of large-scale datasets, advanced searching and data mining. Internally, we have restructured the database models to rationalize the representation of genes and to prepare the system to accept the genome sequences of three additional Caenorhabditis species over the coming year.
21143930
An I/O Optimal and Scalable Skyline Query Algorithm
Given a set of d-dimensional points, skyline query returns the points that are not dominated by any other point on all dimensions. Currently, BBS (branch-and-bound skyline) is the most efficient skyline processing method over static data in a centralized setting. Although BBS has some desirable features (e.g., I/O optimal and flexibility), it requires large main-memory consumption. In this paper, we present an improved skyline computation algorithm based on best-first nearest neighbor search, called IBBS, which captures the optimal I/O and less memory space (i.e., IBBS visits and stores only those entries that contribute to the final skyline). Its core enables several effective pruning strategies to discard non-qualifying entries. Extensive experimental evaluations show that IBBS outperforms BBS in both scalability and efficiency for most cases, especially in low dimensions.
9361697
The centrality of pivotal points in the evolution of scientific networks
In this paper, we describe the development of CiteSpace as an integrated environment for identifying and tracking thematic trends in scientific literature. The goal is to simplify the process of finding not only highly cited clusters of scientific articles, but also pivotal points and trails that are likely to characterize fundamental transitions of a knowledge domain as a whole. The trails of an advancing research field are captured through a sequence of snapshots of its intellectual structure over time in the form of Pathfinder networks. These networks are subsequently merged with a localized pruning algorithm. Pivotal points in the merged network are algorithmically identified and visualized using the betweenness centrality metric. An example of finding clinical evidence associated with reducing risks of heart diseases is included to illustrate how CiteSpace could be used. The contribution of the work is its integration of various change detection algorithms and interactive visualization capabilities to simply users' tasks.
12536250
Generalised similarity analysis and pathfinder network scaling
Abstract This paper introduces a generic approach to the development of hypermedia information systems. This approach emphasises the role of intrinsic inter-document relationships in structuring and visualising a large hypermedia information space. In this paper, we illustrate the use of this approach based on three types of similarity measurements: hypertext linkage, content similarity and usage patterns. Salient patterns in these relationships are extracted and visualised in a simple and intuitive associated network. The spatial layout of a visualisation is optimised such that closely related documents are placed near to each other and only those intrinsic connections among them are shown to users as automatically generated virtual links. This approach supports self-organised information space transformation based on usage patterns and other feedback such that the visual structure of the information space is incrementally tailored to users' search and browsing styles.
45076304
Spatial Semantic Virtual Worlds: The Structural Duality and Beyond