scholarly journals Identification of Novel Potential Genes Involved in Cancer by Integrated Comparative Analyses

2020 ◽  
Vol 21 (24) ◽  
pp. 9560
Author(s):  
Francesco Monticolo ◽  
Emanuela Palomba ◽  
Maria Luisa Chiusano

The main hallmarks of cancer diseases are the evasion of programmed cell death, uncontrolled cell division, and the ability to invade adjacent tissues. The explosion of omics technologies offers challenging opportunities to identify molecular agents and processes that may play relevant roles in cancer. They can support comparative investigations, in one or multiple experiments, exploiting evidence from one or multiple species. Here, we analyzed gene expression data from induction of programmed cell death and stress response in Homo sapiens and compared the results with Saccharomyces cerevisiae gene expression during the response to cell death. The aim was to identify conserved candidate genes associated with Homo sapiens cell death, favored by crosslinks based on orthology relationships between the two species. We identified differentially-expressed genes, pathways that are significantly dysregulated across treatments, and characterized genes among those involved in induced cell death. We investigated on co-expression patterns and identified novel genes that were not expected to be associated with death pathways, that have a conserved pattern of expression between the two species. Finally, we analyzed the resulting list by HumanNet and identified new genes predicted to be involved in cancer. The data integration and the comparative approach between distantly-related reference species that were here exploited pave the way to novel discoveries in cancer therapy and also contribute to detect conserved genes potentially involved in programmed cell death.

2016 ◽  
Vol 12 (4) ◽  
pp. 2976-2981 ◽  
Author(s):  
Xia Zhang ◽  
Riming Liu ◽  
Baohua Huang ◽  
Xiaolu Zhang ◽  
Weijuan Yu ◽  
...  

2018 ◽  
Vol 19 (7) ◽  
pp. 2064 ◽  
Author(s):  
Mingliang Jiang ◽  
Xiangshu Dong ◽  
Hong Lang ◽  
Wenxing Pang ◽  
Zongxiang Zhan ◽  
...  

Orphan genes, also called lineage-specific genes (LSGs), are important for responses to biotic and abiotic stresses, and are associated with lineage-specific structures and biological functions. To date, there have been no studies investigating gene number, gene features, or gene expression patterns of orphan genes in Brassica rapa. In this study, 1540 Brassica-specific genes (BSGs) and 1824 Cruciferae-specific genes (CSGs) were identified based on the genome of Brassica rapa. The genic features analysis indicated that BSGs and CSGs possessed a lower percentage of multi-exon genes, higher GC content, and shorter gene length than evolutionary-conserved genes (ECGs). In addition, five types of BSGs were obtained and 145 out of 529 real A subgenome-specific BSGs were verified by PCR in 51 species. In silico and semi-qPCR, gene expression analysis of BSGs suggested that BSGs are expressed in various tissue and can be induced by Plasmodiophora brassicae. Moreover, an A/C subgenome-specific BSG, BSGs1, was specifically expressed during the heading stage, indicating that the gene might be associated with leafy head formation. Our results provide valuable biological information for studying the molecular function of BSGs for Brassica-specific phenotypes and biotic stress in B. rapa.


2021 ◽  
Author(s):  
Taylor Reiter ◽  
Rachel Montpetit ◽  
Ron Runnebaum ◽  
C. Titus Brown ◽  
Ben Montpetit

AbstractGrapes grown in a particular geographic region often produce wines with consistent characteristics, suggesting there are site-specific factors driving recurrent fermentation outcomes. However, our understanding of the relationship between site-specific factors, microbial metabolism, and wine fermentation outcomes are not well understood. Here, we used differences in Saccharomyces cerevisiae gene expression as a biosensor for differences among Pinot noir fermentations from 15 vineyard sites. We profiled time series gene expression patterns of primary fermentations, but fermentations proceeded at different rates, making analyzes of these data with conventional differential expression tools difficult. This led us to develop a novel approach that combines diffusion mapping with continuous differential expression analysis. Using this method, we identified vineyard specific deviations in gene expression, including changes in gene expression correlated with the activity of the non-Saccharomyces yeast Hanseniaspora uvarum, as well as with initial nitrogen concentrations in grape musts. These results highlight novel relationships between site-specific variables and Saccharomyces cerevisiae gene expression that are linked to repeated wine fermentation outcomes. In addition, we demonstrate that our analysis approach can extract biologically relevant gene expression patterns in other contexts (e.g., hypoxic response of Saccharomyces cerevisiae), indicating that this approach offers a general method for investigating asynchronous time series gene expression data.ImportanceWhile it is generally accepted that foods, in particular wine, possess sensory characteristics associated with or derived from their place of origin, we lack knowledge of the biotic and abiotic factors central to this phenomenon. We have used Saccharomyces cerevisiae gene expression as a biosensor to capture differences in fermentations of Pinot noir grapes from 15 vineyards across two vintages. We find that gene expression by non-Saccharomyces yeasts and initial nitrogen content in the grape must correlates with differences in gene expression among fermentations from these vintages. These findings highlight important relationships between site-specific variables and gene expression that can be used to understand, or possibly modify, wine fermentation outcomes. Our work also provides a novel analysis method for investigating asynchronous gene expression data sets that is able to reveal both global shifts and subtle differences in gene expression due to varied cell – environment interactions.


2020 ◽  
Author(s):  
Minsheng Hao ◽  
Kui Hua ◽  
Xuegong Zhang

AbstractRecent developments of spatial transcriptomic sequencing technologies provide powerful tools for understanding cells in the physical context of tissue micro-environments. A fundamental task in spatial gene expression analysis is to identify genes with spatially variable expression patterns, or spatially variable genes (SVgenes). Several computational methods have been developed for this task. Their high computational complexity limited their scalability to the latest and future large-scale spatial expression data.We present SOMDE, an efficient method for identifying SVgenes in large-scale spatial expression data. SOMDE uses selforganizing map (SOM) to cluster neighboring cells into nodes, and then uses a Gaussian Process to fit the node-level spatial gene expression to identify SVgenes. Experiments show that SOMDE is about 5-50 times faster than existing methods with comparable results. The adjustable resolution of SOMDE makes it the only method that can give results in ~5 minutes in large datasets of more than 20,000 sequencing sites. SOMDE is available as a python package on PyPI at https://pypi.org/project/somde.


Author(s):  
Crescenzio Gallo

The possible applications of modeling and simulation in the field of bioinformatics are very extensive, ranging from understanding basic metabolic paths to exploring genetic variability. Experimental results carried out with DNA microarrays allow researchers to measure expression levels for thousands of genes simultaneously, across different conditions and over time. A key step in the analysis of gene expression data is the detection of groups of genes that manifest similar expression patterns. In this chapter, the authors examine various methods for analyzing gene expression data, addressing the important topics of (1) selecting the most differentially expressed genes, (2) grouping them by means of their relationships, and (3) classifying samples based on gene expressions.


2020 ◽  
Vol 21 (7) ◽  
pp. 2399
Author(s):  
Woan Ting Tay ◽  
Yi-Hsien Fang ◽  
Suet Theng Beh ◽  
Yen-Wen Liu ◽  
Ling-Wei Hsu ◽  
...  

Aim: Immunological checkpoint therapy is considered a powerful method for cancer therapy and acts by re-activating autologous T cells to kill the cancer cell. Myocarditis cases have been reported in cancer patients after immunological therapy; for example, nivolumab treatment is a monoclonal antibody that blocks programmed cell death-1/programmed cell death ligand-1 ligand interaction. This project provided insight into the inflammatory response as a benchmark to investigate the potential cardiotoxic effect of T cell response to the programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) axis in regulating cardiomyocyte injury in vitro. Methods and Results: We investigated cardiomyopathy resulted from the PD-1/PD-L1 axis blockade using the anti-PD-1 antibody in Rockefeller University embryonic stem cells-derived cardiomyocytes (RUES2-CMs) and a melanoma tumor-bearing murine model. We found that nivolumab alone did not induce inflammatory-related proteins, including PD-L1 expression, and did not induce apoptosis, which was contrary to doxorubicin, a cardiotoxic chemotherapy drug. However, nivolumab was able to exacerbate the immune response by increasing cytokine and inflammatory gene expression in RUES2-CMs when co-cultured with CD4+ T lymphocytes and induced apoptosis. This effect was not observed when RUES2-CMs were co-cultured with CD8+ T lymphocytes. The in vivo model showed that the heart function of tumor-bearing mice was decreased after treatment with anti-PD-1 antibody and demonstrated a dilated left ventricle histological examination. The dilated left ventricle was associated with an infiltration of CD4+ and CD8+ T lymphocytes into the myocardium. PD-L1 and inflammatory-associated gene expression were significantly increased in anti-PD-1-treated tumor-bearing mice. Cleaved caspase-3 and mouse plasma cardiac troponin I expressions were increased significantly. Conclusion: PD-L1 expression on cardiomyocytes suppressed T-cell function. Blockade of PD-1 by nivolumab enhanced cardiomyocyte inflammation and apoptosis through the enhancement of T-cell response towards cardiomyocytes.


2008 ◽  
Vol 5 (2) ◽  
Author(s):  
Krzysztof Borowski ◽  
Jung Soh ◽  
Christoph W. Sensen

SummaryThe need for novel methods of visualizing microarray data is growing. New perspectives are beneficial to finding patterns in expression data. The Bluejay genome browser provides an integrative way of visualizing gene expression datasets in a genomic context. We have now developed the functionality to display multiple microarray datasets simultaneously in Bluejay, in order to provide researchers with a comprehensive view of their datasets linked to a graphical representation of gene function. This will enable biologists to obtain valuable insights on expression patterns, by allowing them to analyze the expression values in relation to the gene locations as well as to compare expression profiles of related genomes or of di erent experiments for the same genome.


2020 ◽  
Vol 71 (16) ◽  
pp. 4812-4827 ◽  
Author(s):  
Mei Bai ◽  
Minjian Liang ◽  
Bin Huai ◽  
Han Gao ◽  
Panpan Tong ◽  
...  

Abstract The secretory cavity is a typical structure in Citrus fruit and is formed by schizolysigeny. Previous reports have indicated that programmed cell death (PCD) is involved in the degradation of secretory cavity cells in the fruit, and that the spatio-temporal location of calcium is closely related to nuclear DNA degradation in this process; however, the molecular mechanisms underlying this Ca2+ regulation remain largely unknown. Here, we identified CgCaN that encodes a Ca2+-dependent DNase in the fruit of Citrus grandis ‘Tomentosa’, the function of which was studied using calcium ion localization, DNase activity assays, in situ hybridization, and protein immunolocalization. The results suggested that the full-length cDNA of CgCaN contains an ORF of 1011 bp that encodes a protein 336 amino acids in length with a SNase-like functional domain. CgCaN digests dsDNA at neutral pH in a Ca2+-dependent manner. In situ hybridization signals of CgCaN were particularly distributed in the secretory cavity cells. Ca2+ and Ca2+-dependent DNases were mainly observed in the condensed chromatin and in the nucleolus. In addition, spatio-temporal expression patterns of CgCaN and its protein coincided with the time-points that corresponded to chromatin degradation and nuclear rupture during the PCD in the development of the fruit secretory cavity. Taken together, our results suggest that Ca2+-dependent DNases play direct roles in nuclear DNA degradation during the PCD of secretory cavity cells during Citrus fruit development. Given the consistency of the expression patterns of genes regulated by calmodulin (CaM) and calcium-dependent protein kinases (CDPK) and the dynamics of calcium accumulation, we speculate that CaM and CDPK proteins might be involved in Ca2+ transport from the extracellular walls through the cytoplasm and into the nucleus to activate CgCaN for DNA degradation.


Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1089 ◽  
Author(s):  
Rocio Enriquez-Gasca ◽  
Poppy A. Gould ◽  
Helen M. Rowe

The human genome has been under selective pressure to evolve in response to emerging pathogens and other environmental challenges. Genome evolution includes the acquisition of new genes or new isoforms of genes and changes to gene expression patterns. One source of genome innovation is from transposable elements (TEs), which carry their own promoters, enhancers and open reading frames and can act as ‘controlling elements’ for our own genes. TEs include LINE-1 elements, which can retrotranspose intracellularly and endogenous retroviruses (ERVs) that represent remnants of past retroviral germline infections. Although once pathogens, ERVs also represent an enticing source of incoming genetic material that the host can then repurpose. ERVs and other TEs have coevolved with host genes for millions of years, which has allowed them to become embedded within essential gene expression programmes. Intriguingly, these host genes are often subject to the same epigenetic control mechanisms that evolved to combat the TEs that now regulate them. Here, we illustrate the breadth of host gene regulation through TEs by focusing on examples of young (The New), ancient (The Old), and disease-causing (The Ugly) TE integrants.


Sign in / Sign up

Export Citation Format

Share Document