Understanding the mechanism of pathogenicity through interactome studies between Arachis hypogaea L. and Aspergillus flavus.

Aspergillus flavus (A. flavus) infects the peanut seeds during pre-and post-harvest stages, causing seed quality destruction for humans and livestock consumption. Even though many resistant varieties were developed, the molecular mechanism of defense interactions of peanut against A. flavus still needs further investigation. Hence, an interologous host-pathogen protein interaction (HPPI) network was constructed to understand the subcellular level interaction mechanism between peanut and A. flavus. Out of the top 10 hub proteins of both organisms, protein phosphatase 2C and cyclic nucleotide-binding/kinase domain-containing protein and different ribosomal proteins were identified as candidate proteins involved in defense. Functional annotation and subcellular localization based characterization of HPPI identified protein SGT1 homolog, calmodulin and Rac-like GTP-binding proteins to be involved in defense response against fungus. The relevance of HPPI in infectious conditions was assessed using two transcriptome data which identified the interplay of host kinase class R proteins, bHLH TFs and cell wall related proteins to impart resistance against pathogen infection. Further, the pathogenicity analysis identified glycogen phosphorylase and molecular chaperone and allergen Mod-E/Hsp90/Hsp1 as potential pathogen targets to enhance the host defense mechanism. Hence, the computationally predicted host-pathogen PPI network could provide valuable support for molecular biology experiments to understand the host-pathogen interaction. SIGNIFICANCE: Protein-protein interactions execute significant cellular interactions in an organism and are influenced majorly by stress conditions. Here we reported the host-pathogen protein-protein interaction between peanut and A. flavus, and a detailed network analysis based on function, subcellular localization, gene co-expression, and pathogenicity was performed. The network analysis identified key proteins such as host kinase class R proteins, calmodulin, SGT1 homolog, Rac-like GTP-binding proteins bHLH TFs and cell wall related to impart resistance against pathogen infection. We observed the interplay of defense related proteins and cell wall related proteins predominantly, which could be subjected to further studies. The network analysis described in this study could be applied to understand other host-pathogen systems generally.

Immune response gene coexpression network analysis of Arachis hypogaea infected with Aspergillus flavus.

Aspergillus flavus (A. flavus) infection and aflatoxin contamination is a major bottleneck for peanut cultivation and value chain industry. In this study, a transcriptomic network study was conducted by retrieving publically available RNA-seq datasets of resistant and susceptible peanut varieties infected by A. flavus separately to understand the peanut defense mechanism against A. flavus. The gene expression analysis revealed differentially expressed genes (DEGs) in response to the different levels of infection and coexpression network of DEGs deciphered hub genes involved in the immune process in resistant and susceptible varieties. The interplay of resistance conferring genes and cell wall related genes was observed through functional enrichment analysis in response to pathogen infection and identified few key genes such as Protein P21, R genes, Pattern Recognition Receptor genes, Pectinesterases, Laccase and Thaumatin-like protein 1b as candidate genes in imparting immune response against A. flavus.

Integrated transcriptome interactome study of oncogenes and tumor suppressor genes in breast cancer.

Breast cancer is the leading cause for mortality among women worldwide. Dysregulation of oncogenes and tumor suppressor genes is the major reason for the cause of cancer. Understanding these genes will provide clues and insights about their regulatory mechanism and their interplay in cancer. In the present study, an attempt is made to compare the functional characteristics and interactions of oncogenes and tumor suppressor genes to understand their biological role. 431 breast cancer samples from seven publicly available microarray datasets were collected and analysed using GEO2R tool. The identified 416 differentially expressed genes were classified into five gene sets as oncogenes (OG), tumor suppressor genes (TSG), druggable genes, essential genes and other genes. The gene sets were subjected to various analysis such as enrichment analysis (viz., GO, Pathways, Diseases and Drugs), network analysis, calculation of mutation frequencies and Guanine-Cytosine (GC) content. From the results, it was observed that the OG were having high GC content as well as high interactions than TSG. Moreover, the OG are found to have frequent mutations than TSG. The enrichment analysis results suggest that the oncogenes are involved in positive regulation of cellular protein metabolic process, macromolecule biosynthetic process and majorly in cell cycle and focal adhesion pathway in cancer. It was also found that these oncogenes are involved in other diseases such as skin diseases and viral infections. Collagenase, paclitaxel and docetaxel are some of the drugs found to be enriched for oncogenes.

Expression Data Analysis for the Identification of Potential Biomarker of Pregnancy Associated Breast Cancer.

Breast cancer affects every 1 of 3000 pregnant women or in the first post-partum year is referred as Pregnancy Associated Breast Cancer (PABC) in mid 30s. Even-though rare disease, classified under hormone receptor negative status which metastasis quickly to other parts by extra cellular matrix degradation. Hence it is important to find an optimal treatment option for a PABC patient. Also additional care should be taken to choose the drug; in order to avoid fetal malformation and post-partum stage side-effects. The adaptation of target based therapy in the clinical practice may help to substitute the mastectomy treatment. Recent studies suggested that certain altered Post Translational Modifications (PTMs) may be an indicative of breast cancer progression; an attempt is made to consider the over represented PTM as a parameter for gene selection. The public dataset of PABC from GEO were examined to select Differentially Expressed Genes (DEG). The corresponding PTMs for DEG were collected and association between them was found using data mining technique. Usually clustering algorithm has been applied for the study of gene expression with drawback of clustering of gene products based on specified features. But association rule mining method overcome this shortcoming and determines the useful and in depth relationships. From the association, genes were selected to study the interactions and pathways. These studies emphasis that the genes KLF12, FEN1 MUC1 and SP110, can be chosen as target, which control cancer development, without any harm to pregnancy as well as fetal developmental process.