scholarly journals Dynamic Clustering of Gene Expression

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.

2021 ◽  
Vol 22 (12) ◽  
pp. 6556
Author(s):  
Junjun Huang ◽  
Xiaoyu Li ◽  
Xin Chen ◽  
Yaru Guo ◽  
Weihong Liang ◽  
...  

ATP-binding cassette (ABC) transporter proteins are a gene super-family in plants and play vital roles in growth, development, and response to abiotic and biotic stresses. The ABC transporters have been identified in crop plants such as rice and buckwheat, but little is known about them in soybean. Soybean is an important oil crop and is one of the five major crops in the world. In this study, 255 ABC genes that putatively encode ABC transporters were identified from soybean through bioinformatics and then categorized into eight subfamilies, including 7 ABCAs, 52 ABCBs, 48 ABCCs, 5 ABCDs, 1 ABCEs, 10 ABCFs, 111 ABCGs, and 21 ABCIs. Their phylogenetic relationships, gene structure, and gene expression profiles were characterized. Segmental duplication was the main reason for the expansion of the GmABC genes. Ka/Ks analysis suggested that intense purifying selection was accompanied by the evolution of GmABC genes. The genome-wide collinearity of soybean with other species showed that GmABCs were relatively conserved and that collinear ABCs between species may have originated from the same ancestor. Gene expression analysis of GmABCs revealed the distinct expression pattern in different tissues and diverse developmental stages. The candidate genes GmABCB23, GmABCB25, GmABCB48, GmABCB52, GmABCI1, GmABCI5, and GmABCI13 were responsive to Al toxicity. This work on the GmABC gene family provides useful information for future studies on ABC transporters in soybean and potential targets for the cultivation of new germplasm resources of aluminum-tolerant soybean.


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.


2001 ◽  
Vol 5 (4) ◽  
pp. 161-170 ◽  
Author(s):  
DAVID GERHOLD ◽  
MEIQING LU ◽  
JIAN XU ◽  
CHRISTOPHER AUSTIN ◽  
C. THOMAS CASKEY ◽  
...  

Oligonucleotide DNA microarrays were investigated for utility in measuring global expression profiles of drug metabolism genes. This study was performed to investigate the feasibility of using microarray technology to minimize the long, expensive process of testing drug candidates for safety in animals. In an evaluation of hybridization specificity, microarray technology from Affymetrix distinguished genes up to a threshold of ∼90% DNA identity. Oligonucleotides representing human cytochrome P-450 gene CYP3A5 showed heterologous hybridization to CYP3A4 and CYP3A7 RNAs. These genes could be clearly distinguished by selecting a subset of oligonucleotides that hybridized selectively to CYP3A5. Further validation of the technology was performed by measuring gene expression profiles in livers of rats treated with vehicle, 3-methylcholanthrene (3MC), phenobarbital, dexamethasone, or clofibrate and by confirming data for six genes using quantitative RT-PCR. Responses of drug metabolism genes, including CYPs, epoxide hydrolases ( EHs), UDP-glucuronosyl transferases ( UGTs), glutathione sulfotransferases ( GSTs), sulfotransferases ( STs), drug transporter genes, and peroxisomal genes, to these well-studied compounds agreed well with, and extended, published observations. Additional gene regulatory responses were noted that characterize metabolic effects or stress responses to these compounds. Thus microarray technology can provide a facile overview of gene expression responses relevant to drug metabolism and toxicology.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15258-e15258
Author(s):  
Jayesh Desai ◽  
Jie Wang ◽  
Qing Zhou ◽  
Jun Zhao ◽  
Sanjeev Deva ◽  
...  

e15258 Background: Tislelizumab, an anti-PD-1 monoclonal antibody, showed clinical benefit for patients (pts) with NSCLC alone (NCT02407990, CTR20160872) and in combination with chemotherapy (NCT03432598). Gene expression profiles (GEP) associated with response and resistance to tislelizumab in these studies were assessed. Methods: The GEP of baseline tumor samples from 59 nonsquamous (NSQ) and 42 squamous (SQ) NSCLC pts treated with tislelizumab monotherapy (mono) as ≥1L treatment, and 16 NSQ and 21 SQ pts treated with tislelizumab plus chemotherapy (combo) as 1L treatment were assessed using the 1392-gene HTG GEP EdgeSeq panel. NSQ and SQ cohorts were analyzed separately due to distinct GEP features shown by PCA and t-SNE clustering. Results: Tislelizumab mono and combo showed antitumor activity in NSCLC (Table). In 80 biomarker-evaluable samples, inflamed tumor signatures (inflammatory GEP; antigen presentation GEP) were associated with longer overall survival (log-rank test, NSQ mono: P=0.04, 0.003; NSQ combo: P=0.05, 0.02; SQ combo: P=0.06, 0.06). Monotherapy non-responders (NRs) were clustered into 2 subgroups (NR1, NR2) with distinct GEPs. Compared with responders, NR1 had proliferation signatures (elevated cell cycle [CC] and DNA repair) in both NSQ ( P=0.2, 0.02) and SQ ( P=0.03, 0.4) cohorts, trending toward low inflamed tumor signatures. In NR pts receiving combo, CC and DNA repair signatures were not enriched, and high CC and DNA repair scores were observed in some SQ combo responders versus NRs ( P=0.2, 0.02). NR2 had higher M2 macrophage and Treg cell signatures versus responders in both NSQ and SQ mono, despite high inflamed tumor and low proliferation signatures. NR2 also had increased expression of genes related to immune regulation and angiogenesis, including PIK3CD, CCR2, CD244, IRAK3, and MAP4K1 ( P<0.05) in NSQ, and PIK3CD, CCR2, CD40, CD163, MMP12, VEGFC, and TEK ( P<0.05) in SQ. Conclusions: Clinical benefit in pts with NSCLC receiving tislelizumab (mono or combo) was associated with high inflamed tumor signatures, while elevated immune suppressive cell signatures may indicate resistance. High proliferation signatures were associated with resistance to monotherapy, but not to combination therapy. Both immune- and tumor-intrinsic factors may be considered for validation in future clinical trials. [Table: see text]


2017 ◽  
Vol 69 (1) ◽  
pp. 181-190 ◽  
Author(s):  
Yong Peng ◽  
Huiqin Ma ◽  
Shangwu Chen

Lycium ruthenicum Murr., which belongs to the family Solanaceae, is a resource plant for Chinese traditional medicine and nutraceutical foods. In this study, RNA sequencing was applied to obtain raw reads of L. ruthenicum fruit at different stages of ripening, and a de novo assembly of its sequence was performed. Approximately 52.45 million 100-bp paired-end raw reads were generated from the samples by deep RNA-seq analysis. These short reads were assembled to obtain 164814 contigs, and the contigs were assembled into 84968 non-redundant unigenes using the Trinity method. Assembled sequences were annotated with gene descriptions, gene ontology, clusters of orthologous group and KEGG (Kyoto Encyclopedia of Genes and Genomes)pathway terms. Digital gene expression analysis was applied to compare gene-expression patterns at different fruit developmental stages. These results contribute to existing sequence resources for Lycium spp. during the fruit-ripening stages, which is valuable for further functional studies of genes involved in L. ruthenicum fruit nutraceutical quality.


F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 69 ◽  
Author(s):  
Luca Massimino

The cannabis plant and its active ingredients (i.e., cannabinoids and terpenoids) have been socially stigmatized for half a century. Luckily, with more than 430,000 published scientific papers and about 600 ongoing and completed clinical trials, nowadays cannabis is employed for the treatment of many different medical conditions. Nevertheless, even if a large amount of high-throughput functional genomic data exists, most researchers feature a strong background in molecular biology but lack advanced bioinformatics skills. In this work, publicly available gene expression datasets have been analyzed giving rise to a total of 40,224 gene expression profiles taken from cannabis plant tissue at different developmental stages. The resource presented here will provide researchers with a starting point for future investigations with Cannabis sativa.


2021 ◽  
Author(s):  
Miguel Carda-Dieguez ◽  
Bob T. Rosier ◽  
Sandra Lloret ◽  
Carmen Llena ◽  
Alex Mira

Halitosis is an oral condition caused by an increase in the concentration of volatile sulfur compounds (VSCs), such as methyl mercaptan and hydrogen sulfide, generated as a consequence of bacterial metabolism on the tongue biofilm. Microbial communities on the tongue of halitosis patients have been studied by bacterial culture, 16S rRNA taxonomic studies and metagenomics. However, there are currently no reports on the microbial gene-expression profiles. In this study, we performed RNAseq of tongue coating samples from control individuals and halitosis patients with different levels and composition of VSCs, as determined by gas chromatography. In this metatranscriptomic study, the activity of Streptococcus, Veillonella and Rothia species was associated with halitosis-free individuals while Prevotella, Fusobacterium and Leptotrichia species were associated with halitosis. Although methyl mercaptan is considered an indicator of halitosis, the metatranscriptome of patients in which only this VSC was present in elevated levels was similar to that of halitosis-free individuals. Veillonella dispar, Streptococcus parasanguinis and Rothia mucilaginosa were over-represented in halitosis-free communities in comparison to the rest of the groups, suggesting that these species could be used as a halitosis-free biomarkers. In contrast, the abundance of Prevotella shahi and Fusobacterium nucleatum were significantly higher when hydrogen sulfide concentration was over the established halitosis-threshold, making these species putative halitosis biomarkers. Finally, gene expression profiles showed a significant over-expression of genes involved in L-cysteine and L-homocysteine synthesis in halitosis-free individuals and an over-expression of genes responsible for cysteine degradation into hydrogen sulfide in halitosis patients. In addition, nitrate reduction into nitrite was also over-expressed in halitosis-free patients. In conclusion, halitosis was associated with communities that degrade amino acids and reduce sulfide, whereas tongue communities that produce L-cysteine from hydrogen sulfide and that reduce nitrate were associated with the absence of halitosis. The latter could provide new strategies to treat this condition.


2004 ◽  
Vol 14 (5) ◽  
pp. 984-997 ◽  
Author(s):  
J. Q. Cui ◽  
Y. F. Shi ◽  
H. J. Zhou ◽  
J. Q. Li

The purpose of this study is to investigate changes of gene expression profiles in hydatidiform moles (HM) and choriocarcinoma and to explore causes of trophoblastic hyperplasia. Using cDNA microarray, 4096 genes were analyzed in two pairs of the tissues of HM versus normal villi and in two pairs of normal primary culture trophoblasts versus JAR cell line of choriocarcinoma. The expressions of two genes in normal villi and HM, as well as in JAR and JEG-3, were examined with the help of immunohistochemistry, immunoblot, and reverse transcriptase-polymerase chain reaction in order to confirm the findings of cDNA microarray. Twenty-four genes were upregulated and 65 genes were downregulated in all HM. Four hundred thirty-three genes were upregulated and 380 genes were downregulated in JAR. Forty-six genes were upregulated in both HM and choriocarcinoma, whereas 13 genes were downregulated. Genes associated with the inhibition of cell proliferation were significantly downregulated, whereas genes associated with cell proliferation, malignant transformation, metastasis, and drug resistance were upregulated. Thymidine kinase-1 (TK-1) and small subunit ribonucleotide reductase (RRM-2) were overexpressed in HM, JAR, and JEG-3. The expressions of TK-1 and RRM-2 in moles were positively correlated with proliferative index of trophoblasts. Our results suggest that altered expression of genes exist in HM and choriocarcinoma. Trophoblastic hyperplasia may be involved in the overexpression of DNA synthetic enzymes.


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