scholarly journals SIMULTANEOUSLY SEGMENTING MULTIPLE GENE EXPRESSION TIME COURSES BY ANALYZING CLUSTER DYNAMICS

2009 ◽  
Vol 07 (02) ◽  
pp. 339-356 ◽  
Author(s):  
SATISH TADEPALLI ◽  
NAREN RAMAKRISHNAN ◽  
LAYNE T. WATSON ◽  
BUD MISHRA ◽  
RICHARD F. HELM

We present a new approach to segmenting multiple time series by analyzing the dynamics of cluster formation and rearrangement around putative segment boundaries. This approach finds application in distilling large numbers of gene expression profiles into temporal relationships underlying biological processes. By directly minimizing information-theoretic measures of segmentation quality derived from Kullback-Leibler (KL) divergences, our formulation reveals clusters of genes along with a segmentation such that clusters show concerted behavior within segments but exhibit significant regrouping across segmentation boundaries. The results of the segmentation algorithm can be summarized as Gantt charts revealing temporal dependencies in the ordering of key biological processes. Applications to the yeast metabolic cycle and the yeast cell cycle are described.

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Hai-Yan Yin ◽  
Yong Tang ◽  
Sheng-Feng Lu ◽  
Ling Luo ◽  
Jia-Ping Wang ◽  
...  

As a major alternative therapy in Traditional Chinese Medicine, it has been demonstrated that moxibustion could generate a series of molecular events in blood, spleen, and brain, and so forth. However, what would happen at the moxibustioned site remained unclear. To answer this question, we performed a microarray analysis with skin tissue taken from the moxibustioned site also Zusanli acupoint (ST36) where 15-minute moxibustion stimulation was administrated. The results exhibited 145 upregulated and 72 downregulated genes which responded immediately under physiological conditions, and 255 upregulated and 243 downregulated genes under pathological conditions. Interestingly, most of the pathways and biological processes of the differentially expressed genes (DEGs) under pathological conditions get involved in immunity, while those under physiological conditions are involved in metabolism.


Endocrinology ◽  
2008 ◽  
Vol 149 (10) ◽  
pp. 5107-5117 ◽  
Author(s):  
Agnès Burniat ◽  
Ling Jin ◽  
Vincent Detours ◽  
Natacha Driessens ◽  
Jean-Christophe Goffard ◽  
...  

We studied gene expression profiles in two mouse models of human thyroid carcinoma: the Tg-RET/PTC3 (RP3) and Tg-E7 mice. RP3 fusion gene is the most frequent mutation found in the first wave post-Chernobyl papillary thyroid cancers (PTCs). E7 is an oncoprotein derived from the human papillomavirus 16 responsible for most cervical carcinoma in women. Both transgenic mice develop thyroid hyperplasia followed by solid differentiated carcinoma in older animals. To understand the different steps leading to carcinoma, we analyzed thyroid gene expression in both strains at different ages by microarray technology. Important biological processes were differentially regulated in the two tumor types. In E7 thyroids, cell cycle was the most up-regulated process, an observation consistent with the huge size of these tumors. In RP3 thyroids, contrary to E7 tumors, several human PTC characteristics were observed: overexpression of many immune-related genes, regulation of human PTC markers, up-regulation of EGF-like growth factors and significant regulation of angiogenesis and extracellular matrix remodeling-related genes. However, similarities were incomplete; they did not concern the overall gene expression and were not conserved in old animals. Therefore, RP3 tumors are partial and transient models of human PTC. They constitute a good model, especially in young animals, to study the respective role of the biological processes shared with human PTC and will allow testing drugs targeting these validated variables.


2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Lingling An ◽  
R. W. Doerge

It is well accepted that genes are simultaneously involved in multiple biological processes and that genes are coordinated over the duration of such events. Unfortunately, clustering methodologies that group genes for the purpose of novel gene discovery fail to acknowledge the dynamic nature of biological processes and provide static clusters, even when the expression of genes is assessed across time or developmental stages. By taking advantage of techniques and theories from time frequency analysis, periodic gene expression profiles are dynamically clustered based on the assumption that different spectral frequencies characterize different biological processes. A two-step cluster validation approach is proposed to statistically estimate both the optimal number of clusters and to distinguish significant clusters from noise. The resulting clusters reveal coordinated coexpressed genes. This novel dynamic clustering approach has broad applicability to a vast range of sequential data scenarios where the order of the series is of interest.


2020 ◽  
Author(s):  
Zhiwei Ji ◽  
Dazhi Shang ◽  
Pora Kim ◽  
Mengyuan Yang ◽  
Sijia Wu ◽  
...  

AbstractAltered circadian gene expression may contribute to Alzheimer’s disease (AD) progression. Unfortunately, sampling the central nervous system (CNS) at multiple time points is not feasible. Moreover, there are no AD-related time-series transcriptome datasets available for studying these circadian patterns and their impacts on AD development. In this study, we introduce a novel computational platform, Event-driven Sample Ordering for Circadian Variation Detection (ESOCVD), to reveal rhythmic patterns of gene expression of AD using untimed transcriptome datasets. ESOCVD was applied to 20 untimed gene expression profiles of 16 brain regions from approximately 3000 AD patients in public transcriptome databases. Our analysis revealed five types of circadian alteration patterns in ~2,000 circadian genes in different brain regions of AD patients. Further analyses of additional databases confirmed that our analytical platform can be applied to identify the evolutionary dynamics of circadian variation during the process of AD development. Through the gene expression correlation analysis for our 8 circadian genes identified from AMP-AD MSBB cohorts, we identified stage-specifically enriched biological processes with anticipated context. Gene expression analysis of AD mouse brain tissues further substantiated the predictions of the ESOCVD model. In summary, ESOCVD is highly versatile in bridging circadian research and precision medicine.


Author(s):  
Yonghua Wang ◽  
Yuxuan Liu ◽  
Su Liu ◽  
Bing Wu

The toxicity of arsenic (As) could be influenced by many environmental factors and elements. Iron (Fe) is one of the elements that could be involved in As-induced toxicity. In this study, the interactive effects of Fe and As in HepG2 cells were analyzed based on cytotoxicity and transcriptomic analyses. The results showed that Fe could decrease cell viability and increase mitochondrial depolarization induced by As exposure. Oxidative stress and damage have been proven to be one of the main mechanisms of As toxicity. Our results showed that Fe increased the generation of reactive oxygen species (ROS) and lipid peroxidation product malondialdehyde (MDA) induced by As exposure. Microarray analysis further verified that Fe increased the alteration of gene expression and biological processes related to oxidative stress, cell proliferation, and the apoptotic signaling pathway caused by As exposure. Both results of cytotoxicity and transcriptomic analyses suggest that an increase of Fe in the human body could increase the As-induced toxicity, which should be considered during the health risk assessment of As.


2018 ◽  
Vol 2018 ◽  
pp. 1-11
Author(s):  
Adeyinka Abiola Adetula ◽  
Xiangdong Liu ◽  
Thuy Nhien Tran Thi ◽  
Ali Akbar Bhuiyan ◽  
Xiaoyong Du ◽  
...  

Leucocytes have tremendous health-check importance related to the individual antiviral capacity of pigs and other mammals. However, the molecular mechanism of the immune response of blood leucocytes in pigs is not completely known. This study investigated the leucocyte-count variation before and after poly I:C stimulation in a Duroc–Erhualian F2 population. Pigs with increased and decreased differences in leucocyte counts were coded as increased responder (IR) and decreased responder (DR), respectively. Then, we used microarray technology to compare the gene-expression profiles of both groups of pigs. Transcriptomic analysis identified 129 differentially expressed genes (DEGs) in IR pigs and 136 DEGs in DR pigs. Forty-one common DEGs showed that both groups had similar expression patterns of immune responses. These results illustrated a differential expression in both groups. Furthermore, qPCR experiment was performed to verify the differential-expression profile. Functional annotation of the DEGs indicated that both IR and DR pigs were similar in several biological processes, including innate immune response, and also exhibited distinct differences in biological processes, molecular function, and pathways. These results provided insights into the mechanism underlying the antiviral capacity of pigs.Trial registration numberis CAS Registry Number24939-03-5.


2007 ◽  
Vol 8 (1) ◽  
Author(s):  
Jochen Supper ◽  
Martin Strauch ◽  
Dierk Wanke ◽  
Klaus Harter ◽  
Andreas Zell

2019 ◽  
Vol 10 (5) ◽  
pp. S1-S6 ◽  
Author(s):  
Vahid Mansouri ◽  
Mostafa Rezaei-Tavirani ◽  
Mohammad-Mehdi Zadeh-Esmaeel ◽  
Sina Rezaei-Tavirani ◽  
Mohammadreza Razzaghi ◽  
...  

Introduction: The Mechanism of laser therapy and also its safety are 2 important features of the application of different types of lasers in medicine. This study aims to investigate the critically affected genes after the treatment of squamous cell carcinoma patients. Methods: The gene expression profiles of 4 squamous cell carcinoma patients that were treated via chemoradiotherapy (CRT) plus the laser and 3 similar patients without laser exposure from Gene Expression Omnibus (GEO) were downloaded and were screened to find critical genes via network analysis. The STRING database, Cytoscape software, and the Clue GO plug-in of Cytoscape software were used. Results: The genes HSX70 and NCC27 were determined as neighbors and HSPA1B, CLIC1, RAB13, PPIF, and LCE3D as hub genes. The over-expression of LCE3D was interpreted as the side effect of laser therapy. Apoptosis and the cell cycle were the dominant biological processes regulated by the HSP molecules in the laser-treated patients. Conclusion: The laser affected the main biological processes and simultaneously issued side effects


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 997-997
Author(s):  
Hendrik JM de Jonge ◽  
Peter Valk ◽  
Kim R Kampen ◽  
Arja ter Elst ◽  
Gertjan Kaspers ◽  
...  

Abstract Abstract 997 Poster Board I-19 A high vascular endothelial growth factor-C (VEGFC) mRNA level of primary blasts of pediatric Acute Myeloid Leukemia (AML) patients correlates with increased in vitro drug resistance and slow AML blast disappearance during induction therapy in vivo; measured by higher blast counts on day 15 in the bone marrow and a prolonged interval towards complete remission (HJM de Jonge et al. Clinical Cancer Research 2008). We set out to study both the effect of VEGFC on long term survival in AML and elucidate gene expression profiles associated with VEGFC expression by using Affymetrix HGU133Plus2.0 gene expression data of 100 pediatric and 525 adult AML patients. Pediatric AML patients with a high VEGFC mRNA expression level (i.e. above the median VEGFC expression level) showed a significantly shortened overall survival (P = .041, hazard ratio = 1,81). Among the adult cohort of 525 AML samples, patients with a high VEGFC mRNA level also had significantly reduced overall survival and event free survival (OS and EFS) compared to patients with a low VEGFC level (P < .001, hazard ratio = 1,41 for OS and P = .002, hazard ratio = 1,44 for EFS). The continuous variable VEGFC maintained its prognostic significance for OS and EFS in a multivariate cox-regression model after correction for possible confounding effects of age, white blood cell count, cytogenetic risk group (i.e. favorable, intermediate and unfavorable), NPM1 mutation and FLT3-ITD (P = .031, odds ratio 1.37 for OS and P = .008, odds ratio 1.42 for EFS). Differentially expressed probe sets were identified that distinguished patients with high from those with low VEGFC mRNA expression using a multivariate permutation test in Biometric Research Branch ArrayTools (BRB ArrayTools). Next, gene arrays of the pediatric AML cohort and a publicly available adult AML cohort of 180 gene arrays (Tomasson et al. Blood 2008) were used for validation of these probe sets. Finally, after two validation steps 569 probe sets were found to show differential high expression and 51 probe sets revealed differential low expression in AML with high mRNA levels of VEGFC, representative of distinctive biological processes (represented by GO-categories). Cell proliferation, VEGF receptor activity, signal transduction (e.g. PAK3 and SOS2 which are upstream activators of MEK1) and angiogenesis were upregulated, whereas genes associated with apoptosis (e.g. TIA1 and ANP32A) were found to be down regulated in AML with elevated VEGFC. In conclusion, high VEGFC mRNA expression levels are associated with reduced survival in adult and pediatric AML. Following the analysis of gene expression data in three independent AML cohorts the data suggest the involvement of specific biological processes in AML with (high) VEGFC expression with potential therapeutic impact. Disclosures: No relevant conflicts of interest to declare.


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