Sushmita Paul

Bio: Sushmita Paul is an academic researcher from Indian Institute of Technology, Jodhpur. The author has contributed to research in topics: Cluster analysis & Rough set. The author has an hindex of 12, co-authored 57 publications receiving 575 citations. Previous affiliations of Sushmita Paul include University of Erlangen-Nuremberg & Indian Statistical Institute.

Differential Expression Profile of NLRs and AIM2 in Glioma and Implications for NLRP12 in Glioblastoma

Abstract: Gliomas are the most prevalent primary brain tumors with immense clinical heterogeneity, poor prognosis and survival. The nucleotide-binding domain, and leucine-rich repeat containing receptors (NLRs) and absent-in-melanoma 2 (AIM2) are innate immune receptors crucial for initiation and progression of several cancers. There is a dearth of reports linking NLRs and AIM2 to glioma pathology. NLRs are expressed by cells of innate immunity, including monocytes, macrophages, dendritic cells, endothelial cells, and neutrophils, as well as cells of the adaptive immune system. NLRs are critical regulators of major inflammation, cell death, immune and cancer-associated pathways. We used a data-driven approach to identify NLRs, AIM2 and NLR-associated gene expression and methylation patterns in low grade glioma and glioblastoma, using The Cancer Genome Atlas (TCGA) patient datasets. Since TCGA data is obtained from tumor tissue, comprising of multiple cell populations including glioma cells, endothelial cells and tumor-associated microglia/macrophages we have used multiple cell lines and human brain tissues to identify cell-specific effects. TCGA data mining showed significant differential NLR regulation and strong correlation with survival in different grades of glioma. We report differential expression and methylation of NLRs in glioma, followed by NLRP12 identification as a candidate prognostic marker for glioma progression. We found that Nlrp12 deficient microglia show increased colony formation while Nlrp12 deficient glioma cells show decreased cellular proliferation. Immunohistochemistry of human glioma tissue shows increased NLRP12 expression. Interestingly, microglia show reduced migration towards Nlrp12 deficient glioma cells.

Microarray Time-Series Data Clustering Using Rough-Fuzzy C-Means Algorithm

Abstract: Clustering is one of the important analysis in functional genomics that discovers groups of co-expressed genes from micro array data. In this paper, the application of rough-fuzzy c-means (RFCM)algorithm is presented to discover co-expressed gene clusters. One of the major issues of the RFCM based micro array data clustering is how to select initial prototypes of different clusters. To overcome this limitation, a method is proposed to select initial cluster centers. It enables the RFCM algorithm to converge to an optimum or near optimum solutions and helps to discover co-expressed gene clusters. A method is also introduced based on Dunn's cluster validity index to identify optimum values of different parameters of the initialization method and the RFCM algorithm. The effectiveness of the RFCM algorithm, along with a comparison with other related methods, is demonstrated on five yeast gene expression time-series data sets using Silhouette index, Davies-Bould in index, and gene ontology based analysis.

Model-based genotype-phenotype mapping used to investigate gene signatures of immune sensitivity and resistance in melanoma micrometastasis.

Abstract: In this paper, we combine kinetic modelling and patient gene expression data analysis to elucidate biological mechanisms by which melanoma becomes resistant to the immune system and to immunotherapy. To this end, we systematically perturbed the parameters in a kinetic model and performed a mathematical analysis of their impact, thereby obtaining signatures associated with the emergence of phenotypes of melanoma immune sensitivity and resistance. Our phenotypic signatures were compared with published clinical data on pretreatment tumor gene expression in patients subjected to immunotherapy against metastatic melanoma. To this end, the differentially expressed genes were annotated with standard gene ontology terms and aggregated into metagenes. Our method sheds light on putative mechanisms by which melanoma may develop immunoresistance. Precisely, our results and the clinical data point to the existence of a signature of intermediate expression levels for genes related to antigen presentation that constitutes an intriguing resistance mechanism, whereby micrometastases are able to minimize the combined anti-tumor activity of complementary responses mediated by cytotoxic T cells and natural killer cells, respectively. Finally, we computationally explored the efficacy of cytokines used as low-dose co-adjuvants for the therapeutic anticancer vaccine to overcome tumor immunoresistance.

Robust Rough-Fuzzy C-Means Algorithm: Design and Applications in Coding and Non-coding RNA Expression Data Clustering

Abstract: 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. In this background, different rough-fuzzy clustering algorithms have been shown to be successful for finding overlapping and vaguely defined clusters. However, the crisp lower approximation of a cluster in existing rough-fuzzy clustering algorithms is usually assumed to be spherical in shape, which restricts to find arbitrary shapes of clusters. In this regard, this paper presents a new rough-fuzzy clustering algorithm, termed as robust rough-fuzzy c-means. Each cluster in the proposed 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 proposed algorithm is robust in the sense that it can find overlapping and vaguely defined clusters with arbitrary shapes in noisy environment. An efficient method is presented, based on Pearson's correlation coefficient, to select initial prototypes of different clusters. A method is also introduced based on cluster validity index to identify optimum values of different parameters of the initialization method and the proposed clustering algorithm. The effectiveness of the proposed 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.

Hallmarks of Cancer: New Dimensions

Abstract: 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.

Abstract: 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.