Traditional Hierarchical Clustering Research Articles

ModuleFinder and CoReg: alternative tools for linking gene expression modules with promoter sequences motifs to uncover gene regulation mechanisms in plants.

BackgroundUncovering the key sequence elements in gene promoters that regulate the expression of plant genomes is a huge task that will require a series of complementary methods for prediction, substantial innovations in experimental validation and a much greater understanding of the role of combinatorial control in the regulation of plant gene expression.ResultsTo add to this larger process and to provide alternatives to existing prediction methods, we have developed several tools in the statistical package R. ModuleFinder identifies sets of genes and treatments that we have found to form valuable sets for analysis of the mechanisms underlying gene co-expression. CoReg then links the hierarchical clustering of these co-expressed sets with frequency tables of promoter elements. These promoter elements can be drawn from known elements or all possible combinations of nucleotides in an element of various lengths. These sets of promoter elements represent putative cis-acting regulatory elements common to sets of co-expressed genes and can be prioritised for experimental testing. We have used these new tools to analyze the response of transcripts for nuclear genes encoding mitochondrial proteins in Arabidopsis to a range of chemical stresses. ModuleFinder provided a subset of co-expressed gene modules that are more logically related to biological functions than did subsets derived from traditional hierarchical clustering techniques. Importantly ModuleFinder linked responses in transcripts for electron transport chain components, carbon metabolism enzymes and solute transporter proteins. CoReg identified several promoter motifs that helped to explain the patterns of expression observed.ConclusionModuleFinder identifies sets of genes and treatments that form useful sets for analysis of the mechanisms behind co-expression. CoReg links the clustering tree of expression-based relationships in these sets with frequency tables of promoter elements. These sets of promoter elements represent putative cis-acting regulatory elements for sets of genes, and can then be tested experimentally. We consider these tools, both built on an open source software product to provide valuable, alternative tools for the prioritisation of promoter elements for experimental analysis.

Exploiting homogeneity in protein sequence clusters for construction of protein family hierarchies

In the field of proteomics, protein hierarchies based on sequence analysis have been extensively applied to automate the annotations of new proteins and facilitate the discovery and analysis of protein families. However, the presence of ambiguous similarities in large databases increases the difficulty of delivering protein family hierarchies with favorable sensitivity and specificity. This work develops the HomoClust algorithm that exploits the homogeneity of protein sequences in generating protein family hierarchies. HomoClust improves the clustering quality of traditional hierarchical clustering algorithms by adopting different clustering mechanisms for different levels of sequence similarity. With considering homogeneity detection during clustering process, HomoClust increases the sensitivity of protein clusters without a drop in high specificity.

Hierarchical clustering algorithm for comprehensive orthologous-domain classification in multiple genomes

Ortholog identification is a crucial first step in comparative genomics. Here, we present a rapid method of ortholog grouping which is effective enough to allow the comparison of many genomes simultaneously. The method takes as input all-against-all similarity data and classifies genes based on the traditional hierarchical clustering algorithm UPGMA. In the course of clustering, the method detects domain fusion or fission events, and splits clusters into domains if required. The subsequent procedure splits the resulting trees such that intra-species paralogous genes are divided into different groups so as to create plausible orthologous groups. As a result, the procedure can split genes into the domains minimally required for ortholog grouping. The procedure, named DomClust, was tested using the COG database as a reference. When comparing several clustering algorithms combined with the conventional bidirectional best-hit (BBH) criterion, we found that our method generally showed better agreement with the COG classification. By comparing the clustering results generated from datasets of different releases, we also found that our method showed relatively good stability in comparison to the BBH-based methods.

Analysis of Diffuse Large B-cell Lymphoma Heterogeneity Based on Coupled Two-way Clustering

Microarray technology has proposed a powerful tool in dealing with the heterogeneity of disease. Currently, many methods in the field are based on traditional hierarchical clustering to discover subtypes of disease using a large number of genes on microarray.However, they did not considered that large unrelated noise (genes)may mask significant partitions and correlations of disease samples. To avoid the shortcoming, this paper presented a heterogeneous analysis based on coupled two-way clustering (HCTWC) to search interesting gene signature and find the natural partitions of disease samples. The method was applied to diffuse large B-cell lymphoma (DLBCL) microarray dataset. By identifying significant gene signature, we were able to discover the two new subtypes of DLBCL with survival rate 55% and 25% respectively. The results showed that HCTWC had the potential to be a powerful tool for solving the heterogeneity of disease on gene expression profile.

HIERARCHICAL CLUSTERING FOR COMPLEX DATA

In this paper we introduce a new tree-structured self-organizing neural network called a dynamical growing self-organizing tree (DGSOT). This DGSOT algorithm constructs a hierarchy from top to bottom by division. At each hierarchical level, the DGSOT optimizes the number of clusters, from which the proper hierarchical structure of the underlying data set can be found. We propose a K-level up distribution (KLD) mechanism. This KLD scheme increases the scope for data distribution in the hierarchy, which allows the data mis-clustered in the early stages to be re-evaluated at a later stage increasing the accuracy of the final clustering result. The DGSOT algorithm, combined with the KLD mechanism, overcomes the drawbacks of traditional hierarchical clustering algorithms (e.g., hierarchical agglomerative clustering). The DGSOT algorithm has been tested on two benchmark data sets including gene expression complex data set and we observe that our algorithm extracts patterns with different levels of abstraction. Furthermore, our approach is useful on recognizing features in complex gene expression data. As a dendrogram, these results can be easily displayed for visualization.

Knowledge-assisted recognition of cluster boundaries in gene expression data

DNA microarray technology has made it possible to determine the expression levels of thousands of genes in parallel under multiple experimental conditions. Genome-wide analyses using DNA microarrays make a great contribution to the exploration of the dynamic state of genetic networks, and further lead to the development of new disease diagnosis technologies. An important step in the analysis of gene expression data is to classify genes with similar expression patterns into the same groups. To this end, hierarchical clustering algorithms have been widely used. Major advantages of hierarchical clustering algorithms are that investigators do not need to specify the number of clusters in advance and results are presented visually in the form of a dendrogram. However, since traditional hierarchical clustering methods simply provide results on the statistical characteristics of expression data, biological interpretations of the resulting clusters are not easy, and it requires laborious tasks to unveil hidden biological processes regulated by members in the clusters. Therefore, it has been a very difficult routine for experts. Here, we propose a novel algorithm in which cluster boundaries are determined by referring to functional annotations stored in genome databases. The algorithm first performs hierarchical clustering of gene expression profiles. Then, the cluster boundaries are determined by the Variance Inflation Factor among the Gene Function Vectors, which represents distributions of gene functions in each cluster. Our algorithm automatically specifies a cutoff that leads to functionally independent agglomerations of genes on the dendrogram derived from similarities among gene expression patterns. Finally, each cluster is annotated according to dominant gene functions within the respective cluster. In this paper, we apply our algorithm to two gene expression datasets related to cell cycle and cold stress response in budding yeast Saccharomyces cerevisiae. As a result, we show that the algorithm enables us to recognize cluster boundaries characterizing fundamental biological processes such as the Early G1, Late G1, S, G2 and M phases in cell cycles, and also provides novel annotation information that has not been obtained by traditional hierarchical clustering methods. In addition, using formal cluster validity indices, high validity of our algorithm is verified by the comparison through other popular clustering algorithms, K-means, self-organizing map and AutoClass.

Performance of Fuzzy ART neural network and hierarchical clustering for part-machine grouping based on operation sequences

The problem context for this study is one of identifying families of parts having a similar sequence of operations. This is a prerequisite for the implementation of cellular manufacturing, group technology, just-in-time manufacturing systems and for streamlining material flows in general. Given this problem context, this study develops an experimental procedure to compare the performance of a fuzzy ART neural network, a relatively recent neural network method, with the performance of traditional hierarchical clustering methods. For large, industry-type data sets, the fuzzy ART network, with the modifications proposed here, is capable of performance levels equal or superior to those of the widely used hierarchical clustering methods. However, like other ART networks, Fuzzy ART also results in category proliferation problems, an aspect that continues to require attention for ART networks. However, low execution times and superior solution quality make fuzzy ART a useful addition to the set of tools and techniques now available for group technology and design of cellular manufacturing systems.

K-Means Clustering Methods with Influence Detection

A software program is described that performs K-means clustering with several enhancements. The software system includes the influence detection methodology developed by Cheng and Milligan. As such, the applied user can identify those data points that affect the results of a given cluster analysis. The user interface is interactive and allows for multiple analyses in the same session. Finally, the software can handle data set sizes much larger than those provided for by traditional hierarchical clustering methods.

RECENT RESULTS IN HIERARCHICAL CLUSTERING: I–THE REDUCIBLE NEIGHBORHOODS CLUSTERING ALGORITHM

The clustering of large data sets is of great interest in fields such as pattern recognition, numerical taxonomy, image or speech processing. The traditional Ascendant Hierarchical Algorithm (AHC) cannot be run for sets of more than a few thousand elements. The reducible neighborhoods clustering algorithm, which is presented in this paper, has overtaken the limits of the traditional hierarchical clustering algorithm by generating an exact hierarchy on a large data set. The theoretical justification of this algorithm is the so-called Bruynooghe reducibility principle, that lays down the condition under which the exact hierarchy may be constructed locally, by carrying out aggregations in restricted regions of the representation space. As for the Day and Edelsbrunner algorithm, the maximum theoretical time complexity of the reducible neighborhoods clustering algorithm is O(n2 log n), regardless of the chosen clustering strategy. But the reducible neighborhoods clustering algorithm uses the original data table and its practical performances are by far better than Day and Edelsbrunner’s algorithm, thus allowing the hierarchical clustering of large data sets, i.e. composed of more than 10 000 objects.

A new stochastic path-length tree methodology for constructing communication networks

Network analysis has become a popular method for identifying the communication structure in a system where positional and relational aspects are important. In this paper, a maximum likelihood based methodology is presented that allows for the analysis of binary sociometric data. This methodology provides a network representation via estimated path-length or additive trees that indicate the distance between all pairs of members. The methodology is distinguished from traditional hierarchical clustering based procedures by its direct consideration of the asymmetry in a typical communication process, the simultaneous representation of structural characteristics (e.g., clique membership, clique cohesiveness), and the identification of the specialized communication roles of each member (e.g., opinion leader, liaison). A penalty function algorithm is developed and its performance is investigated via a Monte Carlo analysis with synthetic data. An application examining information flows among managers is presented. Finally, directions for future research are suggested.