Data Mining - Concepts and Techniques.

The hallmarks of cancer conceptualization is a heuristic tool for distilling the vast complexity of cancer phenotypes and genotypes into a provisional set of underlying principles. As knowledge of cancer mechanisms has progressed, other facets of the disease have emerged as potential refinements. Herein, the prospect is raised that phenotypic plasticity and disrupted differentiation is a discrete hallmark capability, and that nonmutational epigenetic reprogramming and polymorphic microbiomes both constitute distinctive enabling characteristics that facilitate the acquisition of hallmark capabilities. Additionally, senescent cells, of varying origins, may be added to the roster of functionally important cell types in the tumor microenvironment. SIGNIFICANCE: Cancer is daunting in the breadth and scope of its diversity, spanning genetics, cell and tissue biology, pathology, and response to therapy. Ever more powerful experimental and computational tools and technologies are providing an avalanche of "big data" about the myriad manifestations of the diseases that cancer encompasses. The integrative concept embodied in the hallmarks of cancer is helping to distill this complexity into an increasingly logical science, and the provisional new dimensions presented in this perspective may add value to that endeavor, to more fully understand mechanisms of cancer development and malignant progression, and apply that knowledge to cancer medicine. 

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Hallmarks of Cancer: New Dimensions

50 Years of Image Analysis

The hallmarks of cancer conceptualization is a heuristic tool for distilling the vast complexity of cancer phenotypes and genotypes into a provisional set of underlying principles. As knowledge of cancer mechanisms has progressed, other facets of the disease have emerged as potential refinements. Herein, the prospect is raised that phenotypic plasticity and disrupted differentiation is a discrete hallmark capability, and that nonmutational epigenetic reprogramming and polymorphic microbiomes both constitute distinctive enabling characteristics that facilitate the acquisition of hallmark capabilities. Additionally, senescent cells, of varying origins, may be added to the roster of functionally important cell types in the tumor microenvironment. SIGNIFICANCE: Cancer is daunting in the breadth and scope of its diversity, spanning genetics, cell and tissue biology, pathology, and response to therapy. Ever more powerful experimental and computational tools and technologies are providing an avalanche of "big data" about the myriad manifestations of the diseases that cancer encompasses. The integrative concept embodied in the hallmarks of cancer is helping to distill this complexity into an increasingly logical science, and the provisional new dimensions presented in this perspective may add value to that endeavor, to more fully understand mechanisms of cancer development and malignant progression, and apply that knowledge to cancer medicine.

Hallmarks of Cancer: New Dimensions.

From bench to bedside

Cluster analysis is a technique that divides a given data set into a set of clusters in such a way that two objects from the same cluster are as similar as possible and the objects from different clusters are as dissimilar as possible. A robust rough-fuzzy \(c\)-means clustering algorithm is applied here to identify clusters having similar objects. Each cluster of the robust rough-fuzzy clustering algorithm is represented by a set of three parameters, namely, cluster prototype, a possibilistic fuzzy lower approximation, and a probabilistic fuzzy boundary. The possibilistic lower approximation helps in discovering clusters of various shapes. The cluster prototype depends on the weighting average of the possibilistic lower approximation and probabilistic boundary. The reported algorithm is robust in the sense that it can find overlapping and vaguely defined clusters with arbitrary shapes in noisy environment. The effectiveness of the clustering algorithm, along with a comparison with other clustering algorithms, is demonstrated on synthetic as well as coding and non-coding RNA expression data sets using some cluster validity indices.

A New Rough-Fuzzy Clustering Algorithm and its Applications

Clustering functionally similar genes helps in understanding the mechanism of a biological pathway. It also provides information of those genes whose biological importance is previously not known. Clustering of genes is highly dependent on the similarity or dissimilarity criterion. Usually, microarray gene expression data is used to cluster genes. However, a microarray data may contain noise that may lead to undesired results. Therefore, incorporating gene ontology information may improve the clustering solutions. In this regard, an integrated dissimilarity measure is introduced for grouping functionally similar genes. It is comprised of city block distance and gene ontology based semantic dissimilarity. While, the city block distance is used to compute distance between two gene expression vectors, gene ontology based semantic dissimilarity measure is used for incorporating biological knowledge. The importance of the integrated dissimilarity measure is shown by incorporating it in different c-means clustering algorithms including rough-fuzzy clustering algorithms. In this work it has been shown that incorporation of integrated dissimilarity measure increases the functional similarity of cluster of genes as compared to the methods that are based on either type of dissimilarity measure. It is also observed that the rough-fuzzy clustering algorithm performs better with the new dissimilarity measure compared to different c-means clustering algorithms.

Integration of Gene Expression and Ontology for Clustering Functionally Similar Genes

With the gaining of knowledge in different branches of biology such as molecular biology, structural biology, and biochemistry, and the advancement of technologies lead to the generation of biological data at a phenomenal rate [286].

Introduction to Pattern Recognition and Bioinformatics

Cervical cancer is a leading severe malignancy throughout the world. Molecular processes and biomarkers leading to tumor progression in cervical cancer are either unknown or only partially understood. An increasing number of studies have shown that microRNAs play an important role in tumorigenesis so understanding the regulatory mechanism of miRNAs in gene-regulatory network will help elucidate the complex biological processes that occur during malignancy. Identification of microRNA-messengerRNA (miRNA-mRNA) regulatory modules will aid deciphering aberrant transcriptional regulatory network in cervical cancer but is computationally challenging. In this regard, an algorithm, termed as relevant and functionally consistent miRNA-mRNA modules (RFCM3), is proposed. It integrates miRNA and mRNA expression data of cervical cancer for identification of potential miRNA-mRNA modules. It selects a miRNA-mRNA module by maximizing relation of mRNAs with miRNA and functional similarity between selected mRNAs. Later using the knowledge of miRNA-miRNA synergistic network different modules are fused and finally a set of modules are generated containing several miRNAs as well as mRNAs. This type of module explains the underlying biological pathways containing multiple miRNAs and mRNAs. The effectiveness of the proposed approach over other existing methods has been demonstrated on a miRNA and mRNA expression data of cervical cancer with respect to enrichment analyses and other standard metrices. The proposed approach was found to generate more robust, integrated, and functionally enriched miRNA-mRNA modules in cervical cancer.

Robust Computational Method for Identification of miRNA-mRNA Modules in Cervical Cancer

Identification of cancer subtypes is critically important for understanding the heterogeneity present in tumors. Integrating information from multiple sources, homogeneous groups for cancer can be identified. However, there is a lack of computational approaches to identify histological subtypes among the patients suffering from different types of cancers. Assigning weight to the biomarkers prior to the integration of multiple information sources for the same set of samples can play an important role in cancer subtypes identification, which has not been explored previously. Sub-typing of cancers can help in analyzing shared molecular profiles between different histological subtypes of solid tumors. A novel method for feature weighting based on robust regression fit is developed in this study. The weight is utilized to find similarity between patients individually from each of the information sources. Here, miRNA and mRNA expression profiles across the same set of samples have been used. Patient-similarity networks, that are generated from each of the expression profiles are then integrated using the approach of Similarity Network Fusion. Finally, Spectral clustering is applied on the fused network to identify similar groups of patients that represent a cancer subtype. The effectiveness of the proposed method has been demonstrated on different data sets.

Sushmita Paul

Papers

A New Rough-Fuzzy Clustering Algorithm and its Applications

Integration of Gene Expression and Ontology for Clustering Functionally Similar Genes

Introduction to Pattern Recognition and Bioinformatics

Robust Computational Method for Identification of miRNA-mRNA Modules in Cervical Cancer

A Feature Weighting-Assisted Approach for Cancer Subtypes Identification from Paired Expression profiles.