Noise resistant generalized parametric validity index of clustering for gene expression data

This article has been made available through the Brunel Open Access Publishing Fund.Validity indices have been investigated for decades. However, since there is no study of noise-resistance performance of these indices in the literature, there is no guideline for determining the best clustering in noisy data sets, especially microarray data sets. In this paper, we propose a generalized parametric validity (GPV) index which employs two tunable parameters α and β to control the proportions of objects being considered to calculate the dissimilarities. The greatest advantage of the proposed GPV index is its noise-resistance ability, which results from the flexibility of tuning the parameters. Several rules are set to guide the selection of parameter values. To illustrate the noise-resistance performance of the proposed index, we evaluate the GPV index for assessing five clustering algorithms in two gene expression data simulation models with different noise levels and compare the ability of determining the number of clusters with eight existing indices. We also test the GPV in three groups of real gene expression data sets. The experimental results suggest that the proposed GPV index has superior noise-resistance ability and provides fairly accurate judgements

Automatic Clustering with Single Optimal Solution

Determining optimal number of clusters in a dataset is a challenging task. Though some methods are available, there is no algorithm that produces unique clustering solution. The paper proposes an Automatic Merging for Single Optimal Solution (AMSOS) which aims to generate unique and nearly optimal clusters for the given datasets automatically. The AMSOS is iteratively merges the closest clusters automatically by validating with cluster validity measure to find single and nearly optimal clusters for the given data set. Experiments on both synthetic and real data have proved that the proposed algorithm finds single and nearly optimal clustering structure in terms of number of clusters, compactness and separation.Comment: 13 pages,4 Tables, 3 figure

Adaptive Double Self-Organizing Map for Clustering Gene Expression Data

This thesis presents a novel clustering technique known as adaptive double self- organizing map (ADSOM) that addresses the issue of identifying the correct number of clusters. ADSOM has a flexible topology and performs clustering and cluster visualization simultaneously, thereby requiring no a priori knowledge about the number of clusters. ADSOM combines features of the popular self-organizing map with two- dimensional position vectors, which serve as a visualization tool to decide the number of clusters. It updates its free parameters during training and it allows convergence of its position vectors to a fairly consistent number of clusters provided that its initial number of nodes is greater than the expected number of clusters. A novel index is introduced based on hierarchical clustering of the final locations of position vectors. The index allows automated detection of the number of clusters, thereby reducing human error that could be incurred from counting clusters visually. The reliance of ADSOM in identifying the number of clusters is proven by applying it to publicly available gene expression data from multiple biological systems such as yeast, human, mouse, and bacteria

SMART: Unique splitting-while-merging framework for gene clustering

Copyright @ 2014 Fa et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Successful clustering algorithms are highly dependent on parameter settings. The clustering performance degrades significantly unless parameters are properly set, and yet, it is difficult to set these parameters a priori. To address this issue, in this paper, we propose a unique splitting-while-merging clustering framework, named “splitting merging awareness tactics” (SMART), which does not require any a priori knowledge of either the number of clusters or even the possible range of this number. Unlike existing self-splitting algorithms, which over-cluster the dataset to a large number of clusters and then merge some similar clusters, our framework has the ability to split and merge clusters automatically during the process and produces the the most reliable clustering results, by intrinsically integrating many clustering techniques and tasks. The SMART framework is implemented with two distinct clustering paradigms in two algorithms: competitive learning and finite mixture model. Nevertheless, within the proposed SMART framework, many other algorithms can be derived for different clustering paradigms. The minimum message length algorithm is integrated into the framework as the clustering selection criterion. The usefulness of the SMART framework and its algorithms is tested in demonstration datasets and simulated gene expression datasets. Moreover, two real microarray gene expression datasets are studied using this approach. Based on the performance of many metrics, all numerical results show that SMART is superior to compared existing self-splitting algorithms and traditional algorithms. Three main properties of the proposed SMART framework are summarized as: (1) needing no parameters dependent on the respective dataset or a priori knowledge about the datasets, (2) extendible to many different applications, (3) offering superior performance compared with counterpart algorithms.National Institute for Health Researc

Integrated Assessment and Prediction of Transcription Factor Binding

Systematic chromatin immunoprecipitation (chIP-chip) experiments have become a central technique for mapping transcriptional interactions in model organisms and humans. However, measurement of chromatin binding does not necessarily imply regulation, and binding may be difficult to detect if it is condition or cofactor dependent. To address these challenges, we present an approach for reliably assigning transcription factors (TFs) to target genes that integrates many lines of direct and indirect evidence into a single probabilistic model. Using this approach, we analyze publicly available chIP-chip binding profiles measured for yeast TFs in standard conditions, showing that our model interprets these data with significantly higher accuracy than previous methods. Pooling the high-confidence interactions reveals a large network containing 363 significant sets of factors (TF modules) that cooperate to regulate common target genes. In addition, the method predicts 980 novel binding interactions with high confidence that are likely to occur in so-far untested conditions. Indeed, using new chIP-chip experiments we show that predicted interactions for the factors Rpn4p and Pdr1p are observed only after treatment of cells with methyl-methanesulfonate, a DNA-damaging agent. We outline the first approach for consistently integrating all available evidences for TF–target interactions and we comprehensively identify the resulting TF module hierarchy. Prioritizing experimental conditions for each factor will be especially important as increasing numbers of chIP-chip assays are performed in complex organisms such as humans, for which “standard conditions” are ill defined

Network motif-based identification of transcription factor-target gene relationships by integrating multi-source biological data

<p>Abstract</p> <p>Background</p> <p>Integrating data from multiple global assays and curated databases is essential to understand the spatio-temporal interactions within cells. Different experiments measure cellular processes at various widths and depths, while databases contain biological information based on established facts or published data. Integrating these complementary datasets helps infer a mutually consistent transcriptional regulatory network (TRN) with strong similarity to the structure of the underlying genetic regulatory modules. Decomposing the TRN into a small set of recurring regulatory patterns, called network motifs (NM), facilitates the inference. Identifying NMs defined by specific transcription factors (TF) establishes the framework structure of a TRN and allows the inference of TF-target gene relationship. This paper introduces a computational framework for utilizing data from multiple sources to infer TF-target gene relationships on the basis of NMs. The data include time course gene expression profiles, genome-wide location analysis data, binding sequence data, and gene ontology (GO) information.</p> <p>Results</p> <p>The proposed computational framework was tested using gene expression data associated with cell cycle progression in yeast. Among 800 cell cycle related genes, 85 were identified as candidate TFs and classified into four previously defined NMs. The NMs for a subset of TFs are obtained from literature. Support vector machine (SVM) classifiers were used to estimate NMs for the remaining TFs. The potential downstream target genes for the TFs were clustered into 34 biologically significant groups. The relationships between TFs and potential target gene clusters were examined by training recurrent neural networks whose topologies mimic the NMs to which the TFs are classified. The identified relationships between TFs and gene clusters were evaluated using the following biological validation and statistical analyses: (1) Gene set enrichment analysis (GSEA) to evaluate the clustering results; (2) Leave-one-out cross-validation (LOOCV) to ensure that the SVM classifiers assign TFs to NM categories with high confidence; (3) Binding site enrichment analysis (BSEA) to determine enrichment of the gene clusters for the cognate binding sites of their predicted TFs; (4) Comparison with previously reported results in the literatures to confirm the inferred regulations.</p> <p>Conclusion</p> <p>The major contribution of this study is the development of a computational framework to assist the inference of TRN by integrating heterogeneous data from multiple sources and by decomposing a TRN into NM-based modules. The inference capability of the proposed framework is verified statistically (<it>e.g</it>., LOOCV) and biologically (<it>e.g</it>., GSEA, BSEA, and literature validation). The proposed framework is useful for inferring small NM-based modules of TF-target gene relationships that can serve as a basis for generating new testable hypotheses.</p

Clustering Algorithms: Their Application to Gene Expression Data

Gene expression data hide vital information required to understand the biological process that takes place in a particular organism in relation to its environment. Deciphering the hidden patterns in gene expression data proffers a prodigious preference to strengthen the understanding of functional genomics. The complexity of biological networks and the volume of genes present increase the challenges of comprehending and interpretation of the resulting mass of data, which consists of millions of measurements; these data also inhibit vagueness, imprecision, and noise. Therefore, the use of clustering techniques is a first step toward addressing these challenges, which is essential in the data mining process to reveal natural structures and iden-tify interesting patterns in the underlying data. The clustering of gene expression data has been proven to be useful in making known the natural structure inherent in gene expression data, understanding gene functions, cellular processes, and subtypes of cells, mining useful information from noisy data, and understanding gene regulation. The other benefit of clustering gene expression data is the identification of homology, which is very important in vaccine design. This review examines the various clustering algorithms applicable to the gene expression data in order to discover and provide useful knowledge of the appropriate clustering technique that will guarantee stability and high degree of accuracy in its analysis procedure