Techniques for clustering gene expression data

Many clustering techniques have been proposed for the analysis of gene expression data obtained from microarray experiments. However, choice of suitable method(s) for a given experimental dataset is not straightforward. Common approaches do not translate well and fail to take account of the data profile. This review paper surveys state of the art applications which recognises these limitations and implements procedures to overcome them. It provides a framework for the evaluation of clustering in gene expression analyses. The nature of microarray data is discussed briefly. Selected examples are presented for the clustering methods considered

Methods for protein complex prediction and their contributions towards understanding the organization, function and dynamics of complexes

Complexes of physically interacting proteins constitute fundamental functional units responsible for driving biological processes within cells. A faithful reconstruction of the entire set of complexes is therefore essential to understand the functional organization of cells. In this review, we discuss the key contributions of computational methods developed till date (approximately between 2003 and 2015) for identifying complexes from the network of interacting proteins (PPI network). We evaluate in depth the performance of these methods on PPI datasets from yeast, and highlight challenges faced by these methods, in particular detection of sparse and small or sub- complexes and discerning of overlapping complexes. We describe methods for integrating diverse information including expression profiles and 3D structures of proteins with PPI networks to understand the dynamics of complex formation, for instance, of time-based assembly of complex subunits and formation of fuzzy complexes from intrinsically disordered proteins. Finally, we discuss methods for identifying dysfunctional complexes in human diseases, an application that is proving invaluable to understand disease mechanisms and to discover novel therapeutic targets. We hope this review aptly commemorates a decade of research on computational prediction of complexes and constitutes a valuable reference for further advancements in this exciting area.Comment: 1 Tabl

DYNAMIC CLUSTERING OF CELL-CYCLE MICROARRAY DATA

The cell cycle is a crucial series of events that are repeated over time, allowing the cell to grow, duplicate, and split. Cell-cycle systems play an important role in cancer and other biological processes. Using gene expression data gained from microarray technology it is possible to group or cluster genes that are involved in the cell-cycle for the purpose of exploring their functional co-regulation. Typically, the goal of clustering methods as applied to gene expression data is to place genes with similar expression patterns or profiles into the same group or cluster for the purpose of inferring the function of unknown genes that cluster with genes of known function. Since a gene may be involved in more than one biological process at any one time, co-regulated genes may not have visually similar expression patterns. Furthermore, the time duration for genes in a biological process may differ, and the number of co-regulated patterns or biological processes shared by two genes may be unknown. Based on this reasoning, biologically realistic gene clusters gained from gene co-regulation may not be accurately identified using traditional clustering methods. By taking advantage of techniques and theories from signal processing, it possible to cluster cell-cycle gene expression profiles using a dynamic perspective under the assumption that different spectral frequencies characterize different biological processes

Application Oriented Analysis of Large Scale Datasets

Diverse application areas, such as social network, epidemiology, and software engineering consist of systems of objects and their relationships. Such systems are generally modeled as graphs. Graphs consist of vertices that represent the objects, and edges that represent the relationships between them. These systems are data intensive and it is important to correctly analyze the data to obtain meaningful information. Combinatorial metrics can provide useful insights for analyzing these systems. In this thesis, we use the graph based metrics such as betweenness centrality, clustering coefficient, articulation points, etc. for analyzing instances of large change in evolving networks (Software Engineering), and identifying points of similarity (Gene Expression Data). Computations of combinatorial properties are expensive and most real world networks are not static. As the network evolves these properties have to be recomputed. In the last part of thesis, we develop a fast algorithm that avoids redundant recomputations of communities in dynamic networks

Vertical wind profile characterization and identification of patterns based on a shape clustering algorithm

Wind power plants are becoming a generally accepted resource in the generation mix of many utilities. At the same time, the size and the power rating of individual wind turbines have increased considerably. Under these circumstances, the sector is increasingly demanding an accurate characterization of vertical wind speed profiles to estimate properly the incoming wind speed at the rotor swept area and, consequently, assess the potential for a wind power plant site. The present paper describes a shape-based clustering characterization and visualization of real vertical wind speed data. The proposed solution allows us to identify the most likely vertical wind speed patterns for a specific location based on real wind speed measurements. Moreover, this clustering approach also provides characterization and classification of such vertical wind profiles. This solution is highly suitable for a large amount of data collected by remote sensing equipment, where wind speed values at different heights within the rotor swept area are available for subsequent analysis. The methodology is based on z-normalization, shape-based distance metric solution and the Ward-hierarchical clustering method. Real vertical wind speed profile data corresponding to a Spanish wind power plant and collected by using a commercialWindcube equipment during several months are used to assess the proposed characterization and clustering process, involving more than 100000 wind speed data values. All analyses have been implemented using open-source R-software. From the results, at least four different vertical wind speed patterns are identified to characterize properly over 90% of the collected wind speed data along the day. Therefore, alternative analytical function criteria should be subsequently proposed for vertical wind speed characterization purposes.The authors are grateful for the financial support from the Spanish Ministry of the Economy and Competitiveness and the European Union —ENE2016-78214-C2-2-R—and the Spanish Education, Culture and Sport Ministry —FPU16/042

Machine Learning Approaches for Cancer Analysis

In addition, we propose many machine learning models that serve as contributions to solve a biological problem. First, we present Zseq, a linear time method that identifies the most informative genomic sequences and reduces the number of biased sequences, sequence duplications, and ambiguous nucleotides. Zseq finds the complexity of the sequences by counting the number of unique k-mers in each sequence as its corresponding score and also takes into the account other factors, such as ambiguous nucleotides or high GC-content percentage in k-mers. Based on a z-score threshold, Zseq sweeps through the sequences again and filters those with a z-score less than the user-defined threshold. Zseq is able to provide a better mapping rate; it reduces the number of ambiguous bases significantly in comparison with other methods. Evaluation of the filtered reads has been conducted by aligning the reads and assembling the transcripts using the reference genome as well as de novo assembly. The assembled transcripts show a better discriminative ability to separate cancer and normal samples in comparison with another state-of-the-art method. Studying the abundance of select mRNA species throughout prostate cancer progression may provide some insight into the molecular mechanisms that advance the disease. In the second contribution of this dissertation, we reveal that the combination of proper clustering, distance function and Index validation for clusters are suitable in identifying outlier transcripts, which show different trending than the majority of the transcripts, the trending of the transcript is the abundance throughout different stages of prostate cancer. We compare this model with standard hierarchical time-series clustering method based on Euclidean distance. Using time-series profile hierarchical clustering methods, we identified stage-specific mRNA species termed outlier transcripts that exhibit unique trending patterns as compared to most other transcripts during disease progression. This method is able to identify those outliers rather than finding patterns among the trending transcripts compared to the hierarchical clustering method based on Euclidean distance. A wet-lab experiment on a biomarker (CAM2G gene) confirmed the result of the computational model. Genes related to these outlier transcripts were found to be strongly associated with cancer, and in particular, prostate cancer. Further investigation of these outlier transcripts in prostate cancer may identify them as potential stage-specific biomarkers that can predict the progression of the disease. Breast cancer, on the other hand, is a widespread type of cancer in females and accounts for a lot of cancer cases and deaths in the world. Identifying the subtype of breast cancer plays a crucial role in selecting the best treatment. In the third contribution, we propose an optimized hierarchical classification model that is used to predict the breast cancer subtype. Suitable filter feature selection methods and new hybrid feature selection methods are utilized to find discriminative genes. Our proposed model achieves 100% accuracy for predicting the breast cancer subtypes using the same or even fewer genes. Studying breast cancer survivability among different patients who received various treatments may help understand the relationship between the survivability and treatment therapy based on gene expression. In the fourth contribution, we have built a classifier system that predicts whether a given breast cancer patient who underwent some form of treatment, which is either hormone therapy, radiotherapy, or surgery will survive beyond five years after the treatment therapy. Our classifier is a tree-based hierarchical approach that partitions breast cancer patients based on survivability classes; each node in the tree is associated with a treatment therapy and finds a predictive subset of genes that can best predict whether a given patient will survive after that particular treatment. We applied our tree-based method to a gene expression dataset that consists of 347 treated breast cancer patients and identified potential biomarker subsets with prediction accuracies ranging from 80.9% to 100%. We have further investigated the roles of many biomarkers through the literature. Studying gene expression through various time intervals of breast cancer survival may provide insights into the recovery of the patients. Discovery of gene indicators can be a crucial step in predicting survivability and handling of breast cancer patients. In the fifth contribution, we propose a hierarchical clustering method to separate dissimilar groups of genes in time-series data as outliers. These isolated outliers, genes that trend differently from other genes, can serve as potential biomarkers of breast cancer survivability. In the last contribution, we introduce a method that uses machine learning techniques to identify transcripts that correlate with prostate cancer development and progression. We have isolated transcripts that have the potential to serve as prognostic indicators and may have significant value in guiding treatment decisions. Our study also supports PTGFR, NREP, scaRNA22, DOCK9, FLVCR2, IK2F3, USP13, and CLASP1 as potential biomarkers to predict prostate cancer progression, especially between stage II and subsequent stages of the disease