Using the bagging approach for biclustering of gene expression data

Several methods have been proposed for microarray data analysis that enables to identify groups of genes with similar expression profiles only under a subset of examples. We propose to improve the performance of these biclustering methods by adapting the approach of bagging to biclustering problems. The principle consists in generating a set of biclusters and aggregating the results. Our method has been tested with success on both synthetic and real datasets.     

Biclustering of human cancer microarray data using co-similarity based co-clustering

Biclustering of gene expression data aims at finding localized patterns in a subspace. A bicluster (sometimes called a co-cluster), in the context of gene expression data, is a set of genes that exhibit similar expression intensity under a subset of experimental features (conditions). Most biclustering algorithms proposed in the literature aim at finding sub-matrices that exhibit some sort of coherence by selecting an initial sub-matrix and iteratively adding or subtracting rows and columns. These algorithms are generally dependent on the initial, hard selection of the gene and condition clusters respectively. In this work, we adapt a recently proposed approach for clustering textual data to find biclusters in gene expression data. Our proposed technique is based on the concept of co-similarity between genes (and between conditions) that exploits weighted higher order paths in a bipartite graph representation of the gene expression data. Therefore, we build statistical relations between genes and between conditions by comparing all genes and conditions before finally extracting biclusters from the data. We show that the proposed technique is able to find meaningful non-overlapping biclusters both on synthetically generated data as well as real cancer data. Our results indicate that the proposed technique is resistant to noise in the data and can successfully retrieve biclusters even in the presence of relatively large amount of noise. We also analyze our results with respect to the discovered genes and observe that our extracted biclusters are supported by biological evidences, such as enrichment of gene functions and biological processes.     

A convolution approach to the circle Hough transform for arbitrary radius

The Hough transform is a well-established family of algorithms for locating and describing geometric figures in an image. However, the computational complexity of the algorithm used to calculate the transform is high when used to target complex objects. As a result, the use of the Hough transform to find objects more complex than lines is uncommon in real-time applications. We describe a convolution method for calculating the Hough transform for finding circles of arbitrary radius. The algorithm operates by performing a three-dimensional convolution of the input image with an appropriate Hough kernel. The use of the fast Fourier transform to calculate the convolution results in a Hough transform algorithm with reduced computational complexity and thus increased speed. Edge detection and other convolution-based image processing operations can be incorporated as part of the transform, which removes the need to perform them with a separate pre-processing or post-processing step. As the Discrete Fourier Transform implements circular convolution rather than linear convolution, consideration must be given to padding the input image before forming the Hough transform.     

GAEBic: A Novel Biclustering Analysis Method for miRNA-Targeted Gene Data Based on Graph Autoencoder

Unlike traditional clustering analysis,the biclustering algorithm works simultaneously on two dimensions of samples (row) and variables (column).In recent years,biclustering methods have been developed rapidly and widely applied in biological data analysis,text clustering,recommendation system and other fields.The traditional clustering algorithms cannot be well adapted to process high-dimensional data and/or large-scale data.At present,most of the biclustering algorithms are designed for the differentially expressed big biological data.However,there is little discussion on binary data clustering mining such as miRNA-targeted gene data.Here,we propose a novel biclustering method for miRNA-targeted gene data based on graph autoencoder named as GAEBic.GAEBic applies graph autoencoder to capture the similarity of sample sets or variable sets,and takes a new irregular clustering strategy to mine biclusters with excellent generalization.Based on the miRNA-targeted gene data of soybean,we benchmark several different types of the biclustering algorithm,and find that GAEBic performs better than Bimax,Bibit and the Spectral Biclustering algorithm in terms of target gene enrichment.This biclustering method achieves comparable performance on the high throughput miRNA data of soybean and it can also be used for other species.     

Binary matrix factorization for analyzing gene expression data

The advent of microarray technology enables us to monitor an entire genome in a single chip using a systematic approach. Clustering, as a widely used data mining approach, has been used to discover phenotypes from the raw expression data. However traditional clustering algorithms have limitations since they can not identify the substructures of samples and features hidden behind the data. Different from clustering, biclustering is a new methodology for discovering genes that are highly related to a subset of samples. Several biclustering models/methods have been presented and used for tumor clinical diagnosis and pathological research. In this paper, we present a new biclustering model using Binary Matrix Factorization (BMF). BMF is a new variant rooted from non-negative matrix factorization (NMF). We begin by proving a new boundedness property of NMF. Two different algorithms to implement the model and their comparison are then presented. We show that the microarray data biclustering problem can be formulated as a BMF problem and can be solved effectively using our proposed algorithms. Unlike the greedy strategy-based algorithms, our proposed algorithms for BMF are more likely to find the global optima. Experimental results on synthetic and real datasets demonstrate the advantages of BMF over existing biclustering methods. Besides the attractive clustering performance, BMF can generate sparse results (i.e., the number of genes/features involved in each biclustering structure is very small related to the total number of genes/features) that are in accordance with the common practice in molecular biology.     

从基因表达数据中挖掘最大的行常量双聚类*

双聚类方法是当前分析基因表达数据的一个重要研究方向,其挖掘目标是发现哪些基因在哪些实验条件下具有相似的表达水平或者关系密切.目前已提出了许多双聚类算法来挖掘不同类型的双聚类,然而其大部分挖掘效率不高.鉴于此,提出了一个新颖的挖掘算法——MRCluster,其主要是用来从原始的基因表达数据中挖掘最大的行常量双聚类模式.就其挖掘效率来说,它采用的是基于Apriori原则的基因扩展深度优先的挖掘策略,并且在挖掘过程中引入了一些新颖的剪枝技术来提高效率.将MRCluster和一个行常量双聚类模式挖掘方法RAP(range support pattern)算法进行比较,从实验结果上可以看出,相比RAP算法,MRCluster算法对在原始的基因表达数据中挖掘最大的行常量双聚类模式具有更好的效率.因此,MRCluster算法能够有效地从原始的基因表达数据中挖掘最大的行常量双聚类.     

CoBi: Pattern Based Co-Regulated Biclustering of Gene Expression Data

Co-regulation is a common phenomenon in gene expression. Finding positively and negatively co-regulated gene clusters from gene expression data is a real need. Existing techniques based on global similarity are unable to detect true up- and down-regulated gene clusters. This paper presents an expression pattern based biclustering technique, CoBi, for grouping both positively and negatively regulated genes from microarray expression data. Regulation pattern and similarity in degree of fluctuation are accounted for while computing similarity between two genes. Unlike traditional biclustering techniques, which use greedy iterative approaches, it uses a BiClust tree that needs single pass over the entire dataset to find a set of biologically relevant biclusters. Biclusters determined from different gene expression datasets by the technique show highly enriched functional categories.     

BicFinder: a biclustering algorithm for microarray data analysis

In the context of microarray data analysis, biclustering allows the simultaneous identification of a maximum group of genes that show highly correlated expression patterns through a maximum group of experimental conditions (samples). This paper introduces a heuristic algorithm called BicFinder (The BicFinder software is available at: ) for extracting biclusters from microarray data. BicFinder relies on a new evaluation function called Average Correspondence Similarity Index (ACSI) to assess the coherence of a given bicluster and utilizes a directed acyclic graph to construct its biclusters. The performance of BicFinder is evaluated on synthetic and three DNA microarray datasets. We test the biological significance using a gene annotation web-tool to show that our proposed algorithm is able to produce biologically relevant biclusters. Experimental results show that BicFinder is able to identify coherent and overlapping biclusters.     

A New Hybrid Cuckoo Search Algorithm for Biclustering of Microarray Gene-Expression Data

ABSTRACT

Biclustering in gene-expression data is a subset of the genes demonstrating consistent patterns over a subset of the conditions. Recently, the most of research in biclustering involving statistical and graph-theoretic approaches by adding or deleting rows and/or columns in the data matrix based on some constraints. This is an exhaustive search of the space, and hence the solutions may not be feasible. The proposed work finds the significant biclusters in large expression data using shuffled cuckoo search with Nelder–Mead (SCS-NM). The diversification and intensification of the search space are obtained through shuffling and simplex NM, respectively. The proposed work is tested on four benchmark datasets, and the results are compared with the swarm intelligence techniques and the various biclustering algorithms. The results show that there is significant improvement in the fitness value of proposed work SCS-NM. In addition, the work determines the biological relevance of the biclusters with Gene Ontology in terms of function, process and component.     

基于加权均方残差的改进双聚类算法*

现有的双聚类算法缺乏发现具有重叠结构双聚类的能力,无法有效发现基因表达数据中隐藏的相应双聚类结构,并且在增删条件过程中均未考虑条件重要性对双聚类结果的影响.针对上述问题,文中提出基于加权均方残差的改进双聚类算法.首先利用重叠率和隶属度控制的模糊划分将基因集划分为初始双聚类,然后在最小化目标函数过程中迭代修改各双簇中条件的权重,最后利用加权的均方残差添加符合条件的基因,删除优化的双聚类中一致波动性不好的基因,得到最终的双聚类集.实验表明,文中算法不仅能生成具有共表达水平大小不同的双簇,并且能将重叠率控制在合理范围内.     

一种新的基于Hough变换的椭圆轮廓检测方法

Hough变换是一种检测曲线的有效方法,但使用传统的Hough变换来检测椭圆计算量过大。为此提出了一种新的基于Hough变换的椭圆轮廓检测方法,该方法利用椭圆中心是平面上所有点中距离椭圆轮廓上点最大距离最小的点这一几何性质,降低了Hough参数空间的维度,从而有效地降低了计算量。使用该方法可以快速地判断一个输入图形的轮廓是否为椭圆。     

BSig: evaluating the statistical significance of biclustering solutions

Statistical evaluation of biclustering solutions is essential to guarantee the absence of spurious relations and to validate the high number of scientific statements inferred from unsupervised data analysis without a proper statistical ground. Most biclustering methods rely on merit functions to discover biclusters with specific homogeneity criteria. However, strong homogeneity does not guarantee the statistical significance of biclustering solutions. Furthermore, although some biclustering methods test the statistical significance of specific types of biclusters, there are no methods to assess the significance of flexible biclustering models. This work proposes a method to evaluate the statistical significance of biclustering solutions. It integrates state-of-the-art statistical views on the significance of local patterns and extends them with new principles to assess the significance of biclusters with additive, multiplicative, symmetric, order-preserving and plaid coherencies. The proposed statistical tests provide the unprecedented possibility to minimize the number of false positive biclusters without incurring on false negatives, and to compare state-of-the-art biclustering algorithms according to the statistical significance of their outputs. Results on synthetic and real data support the soundness and relevance of the proposed contributions, and stress the need to combine significance and homogeneity criteria to guide the search for biclusters.     

SUBic: A Scalable Unsupervised Framework for Discovering High Quality Biclusters

A biclustering algorithm extends conventional clustering techniques to extract all of the meaningful subgroups of genes and conditions in the expression matrix of a microarray dataset. However, such algorithms are very sensitive to input parameters and show poor scalability. This paper proposes a scalable unsupervised biclustering framework, SUBic, to find high quality constant-row biclusters in an expression matrix effectively. A one-dimensional clustering algorithm is proposed to partition the attributes, that is, columns of an expression matrix into disjoint groups based on the similarity of expression values. These groups form a set of short transactions and are used to discover a set of frequent itemsets each of which corresponds to a bicluster. However, a bicluster may include any attribute whose expression value is not similar enough to others, so a bicluster refinement is used to enhance the quality of a bicluster by removing those attributes based on its distribution of expression values. The performance of the proposed method is comparatively analyzed through a series of experiments on synthetic and real datasets.     

Noise-robust algorithm for identifying functionally associated biclusters from gene expression data

Biclusters are subsets of genes that exhibit similar behavior over a set of conditions. A biclustering algorithm is a useful tool for uncovering groups of genes involved in the same cellular processes and groups of conditions under which these processes take place. In this paper, we propose a polynomial time algorithm to identify functionally highly correlated biclusters. Our algorithm identifies (1) gene sets that simultaneously exhibit additive, multiplicative, and combined patterns and allow high levels of noise, (2) multiple, possibly overlapped, and diverse gene sets, (3) biclusters that simultaneously exhibit negatively and positively correlated gene sets, and (4) gene sets for which the functional association is very high. We validate the level of functional association in our method by using the GO database, protein-protein interactions and KEGG pathways.     

基于逻辑运算的离散人工蜂群优化双聚类算法

基因表达数据是由DNA微阵列实验产生的大规模数据矩阵,双聚类算法是挖掘数据矩阵中具有较高相关性的子矩阵,能有效地提取生物学信息.针对当前多目标双聚类优化算法易于陷入早熟和局部最优解等问题,论文提出了基于逻辑运算的离散人工蜂群优化双聚类算法(LOABCB算法),一方面引入人工蜂群算法增强双聚类的全局寻优能力,另一方面通过...     

Experimental correlation analysis of bicluster coherence measures and gene ontology information

Biclustering algorithms have become popular tools for gene expression data analysis. They can identify local patterns defined by subsets of genes and subsets of samples, which cannot be detected by traditional clustering algorithms. In spite of being useful, biclustering is an NP-hard problem. Therefore, the majority of biclustering algorithms look for biclusters optimizing a pre-established coherence measure. Many heuristics and validation measures have been proposed for biclustering over the last 20 years. However, there is a lack of an extensive comparison of bicluster coherence measures on practical scenarios. To deal with this lack, this paper experimentally analyzes 17 bicluster coherence measures and external measures calculated from information obtained in the gene ontologies. In this analysis, results were produced by 10 algorithms from the literature in 19 gene expression datasets. According to the experimental results, a few pairs of strongly correlated coherence measures could be identified, which suggests redundancy. Moreover, the pairs of strongly correlated measures might change when dealing with normalized or non-normalized data and biclusters enriched by different ontologies. Finally, there was no clear relation between coherence measures and assessment using information from gene ontology.     

Random walk biclustering for microarray data

A biclustering algorithm, based on a greedy technique and enriched with a local search strategy to escape poor local minima, is proposed. The algorithm starts with an initial random solution and searches for a locally optimal solution by successive transformations that improve a gain function. The gain function combines the mean squared residue, the row variance, and the size of the bicluster. Different strategies to escape local minima are introduced and compared. Experimental results on several microarray data sets show that the method is able to find significant biclusters, also from a biological point of view.     

Gene interaction – An evolutionary biclustering approach

DNA Microarray experiments form a powerful tool for studying gene expression patterns, in large scale. Sharing of the regulatory mechanism among genes, in an organism, is predominantly responsible for their co-expression. Biclustering aims at finding a subset of similarly expressed genes under a subset of experimental conditions. A small number of genes participate in a cellular process of interest. Again, a gene may be simultaneously involved in a number of cellular processes. In cellular environment, genes interact among themselves to produce enzymes, metabolites, proteins, etc. responsible for a particular function(s).In this study, a simple and novel correlation-based approach is proposed to extract gene interaction networks from biclusters in microarray data. Local search strategy is employed to add (remove) relevant (irrelevant) genes for finer tuning, in multi-objective biclustering framework. Preprocessing is done to preserve strongly correlated gene interaction pairs. Experimental results on time-series gene expression data from Yeast are biologically validated using benchmark databases and literature.