scholarly journals Metatranscriptome Analysis of the Human Fecal Microbiota Reveals Subject-Specific Expression Profiles, with Genes Encoding Proteins Involved in Carbohydrate Metabolism Being Dominantly Expressed

2010 ◽  
Vol 76 (16) ◽  
pp. 5533-5540 ◽  
Author(s):  
Carien C. G. M. Booijink ◽  
Jos Boekhorst ◽  
Erwin G. Zoetendal ◽  
Hauke Smidt ◽  
Michiel Kleerebezem ◽  
...  

ABSTRACT The human gastrointestinal (GI) tract provides home to a complex microbial community, collectively termed microbiota. Although major efforts have been made to describe the diversity and stability of the microbiota, functional studies have been largely restricted to intestinal isolates and include few community studies. The aim of this study was to explore the in situ gene expression of the fecal microbiota and to evaluate the RNA fingerprinting method cDNA-AFLP (cDNA amplified fragment length polymorphism) for this purpose. To this end, cDNA-AFLP analysis of enriched mRNA revealed that two healthy subjects showed highly divergent expression profiles with considerable fluctuations in time. Subsequent excision and sequence determination of bands from the mRNA-enriched profiles resulted in 122 identifiable sequences (transcripts and rRNAs). The classification of retrieved transcripts into functional clusters based on COG (cluster of orthologous genes) annotation showed that most assigned transcripts belonged to the metabolism cluster (26% of all sequences), underlining that even at the very end of the intestinal tract the microbiota is still very active. This study furthermore revealed that cDNA-AFLP is a useful tool to compare gene expression profiles in time in complex microbial communities.

2021 ◽  
Author(s):  
Sean Si Qian Ma ◽  
Luyi Ye ◽  
Fan Zhang ◽  
Tiansheng Xu ◽  
Zai-Si Ji ◽  
...  

Abstract Background: Specific gene expression profiles correlate with recurrence of breast cancer in lymph node-negative patients. In contrast, insufficient knowledge is available regarding tumor-specific gene expression in patients with lymph node metastasis before surgery. Furthermore, such patients experience cumulative incidences of relapse greater than 50%. Methods: Sections of formalin-fixed paraffin embedded (FFPE) were prepared from breast tumors of 37 patients who were followed for at least 5 years. FFPE samples of patients with recurrent ductal breast cancer (n = 25) and 12 FFPE samples of such patients without recurrence were subjected to microarray analysis to identify gene expression profiles specifically associated with positive lymph nodes confirmed during surgery that were accompanied by lymphocytic invasion. Immunohistochemistry was employed to determine the estrogen receptor (ER) status of cancer tissues. All patients were administered tamoxifen after surgery, and this treatment continued for more than 5 years, or until cancer recurred. This strategy eliminated interactions between different therapeutics as potential confounding factors that influenced patients' outcomes.Results: Sixteen genes were expressed at significantly higher levels in patients with ER-positive (+) breast cancer with recurrence compared with those without recurrence. Gene Set Enrichment Analysis of The Kyoto Encyclopedia of Genes and Genomes (KEGG) identified 73 genes encoding olfactory receptors included in the “Olfactory transduction” pathway that were enriched in the ER+ recurrence group (FDR P < 0.05). The KEGG “Histidine metabolism” and “Retinol metabolism” pathways were enriched in patients with ER-negative (–) breast cancer with recurrence (FDR P < 0.05). Conclusions: The present study is the first, to our knowledge, to identify 16 genes encoding proteins with diverse functions as well as 73 genes encoding olfactory receptors. These genes may serve as presurgical biomarkers for the recurrence of ER+ breast cancers with lymph node metastasis before surgery. These findings identify potential therapeutic targets for preventing cancer relapse, particularly after lymph nodes metastasis.


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.


2010 ◽  
Vol 45 (6) ◽  
pp. 379-390 ◽  
Author(s):  
Denis Delić ◽  
Nicole Gailus ◽  
Hans-Werner Vohr ◽  
Mohamed Dkhil ◽  
Saleh Al-Quraishy ◽  
...  

Testosterone has been previously shown to induce persistent susceptibility to Plasmodium chabaudi malaria in otherwise resistant female C57BL/6 mice. Here, we investigate as to whether this conversion coincides with permanent changes of hepatic gene expression profiles. Female mice aged 10–12 weeks were treated with testosterone for 3 weeks; then, testosterone treatment was discontinued for 12 weeks before challenging with 106 P. chabaudi-infected erythrocytes. Hepatic gene expression was examined after 12 weeks of testosterone withdrawal and after subsequent infection with P. chabaudi at peak parasitemia, using Affymetrix microarrays with 22 690 probe sets representing 14 000 genes. The expression of 54 genes was found to be permanently changed by testosterone, which remained changed during malaria infection. Most genes were involved in liver metabolism: the female-prevalent genes Cyp2b9, Cyp2b13, Cyp3a41, Cyp3a44, Fmo3, Sult2a2, Sult3a1, and BC014805 were repressed, while the male-prevalent genes Cyp2d9, Cyp7b1, Cyp4a10, Ugt2b1, Ugt2b38, Hsd3b5, and Slco1a1 were upregulated. Genes encoding different nuclear receptors were not persistently changed. Moreover, testosterone induced persistent upregulation of genes involved in hepatocellular carcinoma such as Lama3 and Nox4, whereas genes involved in immune response such as Ifnγ and Igk-C were significantly decreased. Our data provide evidence that testosterone is able to induce specific and robust long-term changes of gene expression profiles in the female mouse liver. In particular, those changes, which presumably indicate masculinized liver metabolism and impaired immune response, may be critical for the testosterone-induced persistent susceptibility of mice to P. chabaudi malaria.


2005 ◽  
Vol 187 (9) ◽  
pp. 3259-3266 ◽  
Author(s):  
Anyou Wang ◽  
David E. Crowley

ABSTRACT Genome-wide analysis of temporal gene expression profiles in Escherichia coli following exposure to cadmium revealed a shift to anaerobic metabolism and induction of several stress response systems. Disruption in the transcription of genes encoding ribosomal proteins and zinc-binding proteins may partially explain the molecular mechanisms of cadmium toxicity.


2005 ◽  
Vol 21 (3) ◽  
pp. 314-323 ◽  
Author(s):  
Henk P. J. Buermans ◽  
Everaldo M. Redout ◽  
Anja E. Schiel ◽  
René J. P. Musters ◽  
Marian Zuidwijk ◽  
...  

Myocardial right ventricular (RV) hypertrophy due to pulmonary hypertension is aimed at normalizing ventricular wall stress. Depending on the degree of pressure overload, RV hypertrophy may progress to a state of impaired contractile function and heart failure, but this cannot be discerned during the early stages of ventricular remodeling. We tested whether critical differences in gene expression profiles exist between ventricles before the ultimate development of either a compensated or decompensated hypertrophic phenotype. Both phenotypes were selectively induced in Wistar rats by a single subcutaneous injection of either a low or a high dose of the pyrrolizidine alkaloid monocrotaline (MCT). Spotted oligonucleotide microarrays were used to investigate pressure-dependent cardiac gene expression profiles at 2 wk after the MCT injections, between control rats and rats that would ultimately develop either compensated or decompensated hypertrophy. Clustering of significantly regulated genes revealed specific expression profiles for each group, although the degree of hypertrophy was still similar in both. The ventricles destined to progress to failure showed activation of pro-apoptotic pathways, particularly related to mitochondria, whereas the group developing compensated hypertrophy showed blocked pro-death effector signaling via p38-MAPK, through upregulation of MAPK phosphatase-1. In summary, we show that, already at an early time point, pivotal differences in gene expression exist between ventricles that will ultimately develop either a compensated or a decompensated phenotype, depending on the degree of pressure overload. These data reveal genes that may provide markers for the early prediction of clinical outcome as well as potential targets for early intervention.


2019 ◽  
Author(s):  
Billy Zeng ◽  
Benjamin S. Glicksberg ◽  
Patrick Newbury ◽  
Jing Xing ◽  
Ke Liu ◽  
...  

AbstractOne approach to precision medicine is to discover drugs that target molecularly defined diseases. Voluminous cancer patient gene expression profiles have been accumulated in public databases, enabling the creation of a cancer-specific expression signature. By matching this signature to perturbagen-induced gene expression profiles from large drug libraries, researchers can prioritize small molecules that present high potency to reverse expression of signature genes for further experimental testing of their efficacy. This approach has proven to be an efficient and cost-effective way to identify efficacious drug candidates. However, the success of this approach requires multiscale procedures, imposing significant challenges to many labs. Therefore, we present OCTAD: an open workplace for virtually screening compounds targeting precise cancer patient groups using gene expression features. We release OCTAD as a web portal and standalone R workflow to allow experimental and computational scientists to easily navigate the tool. In this work, we describe this tool and demonstrate its potential for precision medicine.


2020 ◽  
Vol 117 (44) ◽  
pp. 27354-27364 ◽  
Author(s):  
Siddhant U. Jain ◽  
Sima Khazaei ◽  
Dylan M. Marchione ◽  
Stefan M. Lundgren ◽  
Xiaoshi Wang ◽  
...  

A high percentage of pediatric gliomas and bone tumors reportedly harbor missense mutations at glycine 34 in genes encoding histone variant H3.3. We find that these H3.3 G34 mutations directly alter the enhancer chromatin landscape of mesenchymal stem cells by impeding methylation at lysine 36 on histone H3 (H3K36) by SETD2, but not by the NSD1/2 enzymes. The reduction of H3K36 methylation by G34 mutations promotes an aberrant gain of PRC2-mediated H3K27me2/3 and loss of H3K27ac at active enhancers containing SETD2 activity. This altered histone modification profile promotes a unique gene expression profile that supports enhanced tumor development in vivo. Our findings are mirrored in G34W-containing giant cell tumors of bone where patient-derived stromal cells exhibit gene expression profiles associated with early osteoblastic differentiation. Overall, we demonstrate that H3.3 G34 oncohistones selectively promote PRC2 activity by interfering with SETD2-mediated H3K36 methylation. We propose that PRC2-mediated silencing of enhancers involved in cell differentiation represents a potential mechanism by which H3.3 G34 mutations drive these tumors.


2015 ◽  
Vol 124 (1_suppl) ◽  
pp. 6S-48S ◽  
Author(s):  
Shin-ya Nishio ◽  
Mitsuru Hattori ◽  
Hideaki Moteki ◽  
Keita Tsukada ◽  
Maiko Miyagawa ◽  
...  

Objectives:We sought to elucidate the gene expression profiles of the causative genes as well as the localization of the encoded proteins involved in hereditary hearing loss.Methods:Relevant articles (as of September 2014) were searched in PubMed databases, and the gene symbols of the genes reported to be associated with deafness were located on the Hereditary Hearing Loss Homepage using localization, expression, and distribution as keywords.Results:Our review of the literature allowed us to systematize the gene expression profiles for genetic deafness in the inner ear, clarifying the unique functions and specific expression patterns of these genes in the cochlea and vestibular endorgans.Conclusions:The coordinated actions of various encoded molecules are essential for the normal development and maintenance of auditory and vestibular function.


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