Long non-coding RNAs (lncRNAs) have been defined as transcripts longer than 200 nucleotides, which lack significant protein coding potential and possess critical roles in diverse cellular processes. Long non-coding RNAs have recently been functionally characterized in plant stress–response mechanisms. In the present study, we perform a comprehensive identification of lncRNAs in response to combined stress induced by salinity and excess of boron in the Lluteño maize, a tolerant maize landrace from Atacama Desert, Chile. We use deep RNA sequencing to identify a set of 48,345 different lncRNAs, of which 28,012 (58.1%) are conserved with other maize (B73, Mo17 or Palomero), with the remaining 41.9% belonging to potentially Lluteño exclusive lncRNA transcripts. According to B73 maize reference genome sequence, most Lluteño lncRNAs correspond to intergenic transcripts. Interestingly, Lluteño lncRNAs presents an unusual overall higher expression compared to protein coding genes under exposure to stressed conditions. In total, we identified 1710 putatively responsive to the combined stressed conditions of salt and boron exposure. We also identified a set of 848 stress responsive potential trans natural antisense transcripts (trans-NAT) lncRNAs, which seems to be regulating genes associated with regulation of transcription, response to stress, response to abiotic stimulus and participating of the nicotianamine metabolic process. Reverse transcription-quantitative PCR (RT-qPCR) experiments were performed in a subset of lncRNAs, validating their existence and expression patterns. Our results suggest that a diverse set of maize lncRNAs from leaves and roots is responsive to combined salt and boron stress, being the first effort to identify lncRNAs from a maize landrace adapted to extreme conditions such as the Atacama Desert. The information generated is a starting point to understand the genomic adaptabilities suffered by this maize to surpass this extremely stressed environment.
BackgroundWhole transcriptome RNA variant analyses have shown that adenosine deaminases acting on RNA (ADAR) enzymes modify a large proportion of cellular RNAs, contributing to transcriptome diversity and cancer evolution. Despite the advances in the understanding of ADAR function in breast cancer, ADAR RNA editing functional consequences are not fully addressed.ResultsWe characterized A to G(I) mRNA editing in 81 breast cell lines, showing increased editing at 3′UTR and exonic regions in breast cancer cells compared to immortalized non-malignant cell lines. In addition, tumors from the BRCA TCGA cohort show a 24% increase in editing over normal breast samples when looking at 571 well-characterized UTRs targeted by ADAR1. Basal-like subtype breast cancer patients with high level of ADAR1 mRNA expression shows a worse clinical outcome and increased editing in their 3′UTRs. Interestingly, editing was particularly increased in the 3′UTRs of ATM, GINS4 and POLH transcripts in tumors, which correlated with their mRNA expression. We confirmed the role of ADAR1 in this regulation using a shRNA in a breast cancer cell line (ZR-75-1).ConclusionsAltogether, these results revealed a significant association between the mRNA editing in genes related to cancer-relevant pathways and clinical outcomes, suggesting an important role of ADAR1 expression and function in breast cancer.Electronic supplementary materialThe online version of this article (10.1186/s40659-018-0185-4) contains supplementary material, which is available to authorized users.
Gastric cancer (GC) is a heterogeneous disease. This heterogeneity applies not only to morphological and phenotypic features but also to geographical variations in incidence and mortality rates. As Chile has one of the highest mortality rates within South America, we sought to define a molecular profile of Chilean GCs (ClinicalTrials.gov identifier: NCT03158571/(FORCE1)). Solid tumor samples and clinical data were obtained from 224 patients, with subsets analyzed by tissue microarray (TMA; n = 90) and next generation sequencing (NGS; n = 101). Most demographic and clinical data were in line with previous reports. TMA data indicated that 60% of patients displayed potentially actionable alterations. Furthermore, 20.5% were categorized as having a high tumor mutational burden, and 13% possessed micro-satellite instability (MSI). Results also confirmed previous studies reporting high Epstein-Barr virus (EBV) positivity (13%) in Chilean-derived GC samples suggesting a high proportion of patients could benefit from immunotherapy. As expected, TP53 and PIK3CA were the most frequently altered genes. However, NGS demonstrated the presence of TP53, NRAS, and BRAF variants previously unreported in current GC databases. Finally, using the Kendall method, we report a significant correlation between EBV+ status and programmed death ligand-1 (PDL1)+ and an inverse correlation between p53 mutational status and MSI. Our results suggest that in this Chilean cohort, a high proportion of patients are potential candidates for immunotherapy treatment. To the best of our knowledge, this study is the first in South America to assess the prevalence of actionable targets and to examine a molecular profile of GC patients.
Co-expression analysis has been widely used to elucidate the functional architecture of genes under different biological processes. Such analysis, however, requires substantial knowledge about programming languages and/or bioinformatics skills. We present webCEMiTool,1 a unique online tool that performs comprehensive modular analyses in a fully automated manner. The webCEMiTool not only identifies co-expression gene modules but also performs several functional analyses on them. In addition, webCEMiTool integrates transcriptomic data with interactome information (i.e., protein-protein interactions) and identifies potential hubs on each network. The tool generates user-friendly html reports that allow users to search for specific genes in each module, as well as check if a module contains genes overrepresented in specific pathways or altered in a specific sample phenotype. We used webCEMiTool to perform a modular analysis of single-cell RNA-seq data of human cells infected with either Zika virus or dengue virus.
ABSTRACT. This report describes the miRQuest -a novel middleware available in a Web server that allows the end user to do the miRNA research in a user-friendly way. It is known that there are many prediction tools for microRNA (miRNA) identification that use different programming languages and methods to realize this task. It is difficult to understand each tool and apply it to diverse datasets and organisms available for miRNA analysis. miRQuest can easily be used by biologists and researchers with limited experience with bioinformatics. We built it using the middleware architecture on a Web platform for miRNA research that performs two main functions: i) integration of different miRNA prediction tools for miRNA identification in a user-friendly environment; and ii) comparison of these prediction tools. In both cases, the user provides sequences (in FASTA format) as an input set for the analysis and comparisons. All the tools were selected on the basis of a survey of the literature on the available tools for miRNA prediction. As results, three different cases of use of the tools are also described, where one is the miRNA identification analysis in 30 different species. Finally, miRQuest seems to be a novel and useful tool; and it is freely available for both benchmarking and miRNA identification at
Background: Endoscopic operations on trachea and bronchi are palliative method of lung cancer common forms treatment. The use of this surgical interventions type in patients with the above pathology improves quality and extends the life span. We summarized the 30-year experience of performing endobronchial operations in patients with lung cancer. Method: In the clinic, endoscopic operations on the trachea and bronchi in lung cancer were performed in 1,720 patients, of which 1384 were men and 336 women. Total number of operations 4781. All patients had complete or partial stenosis of bronchi and trachea. Radical surgery was impossible to perform due to the prevalence of the process, either because of the comorbidity presence. Basically, we used a rigorous Friedel bronchoscope -in 1255 patients, the remaining 465 patients used an Olympus fibrobronchoscope. Rigid bronchoscopy was performed using endotracheal anesthesia, interventions with the use of a fibroblochoscope were performed under local anesthesia. We used three methods of influencing the tumor: laser radiation (1259 patients), electrosurgical method (146 patients) and radiofrequency ablation (315 patients). As a source of laser radiation, we used YAG-Nd laser, with a wavelength of 1064 nm and a power of 40 W. Both contact and non-contact methods of influencing the tumor were used. Electrosurgical operations implemented by a contact method using a conventional surgical coagulator under local anesthesia using fibrobronchoscope. The radiofrequency ablation (RFA) method implies the use of an electron wave at a frequency of 500 kHz. As a power source was used Fotec 150 generator. Operative interventions were performed under local anesthesia with the use of fibrobronchoscopy method. Results: In all 1720 patients we managed to achieve complete or partial trachea and bronchi recanalization. The best results were obtained in patients using the RFA method, complete recanalization was achieved in 85% of patients. The diathermocoagulation method showed significantly lower efficiency (complete patency was restored in 24% of patients) and in 28 patients of this group developed pulmonary hemorrhage, which could not be stopped in 8 patients. The use of the YAG-Nd laser made it possible to restore bronchial patency completely in 64% of patients. Conclusion: 1. Endoscopic surgery for tumor stenosis of the respiratory tract are palliative, but their use can improve the quality of life and prolong the life of patients. 2. The RFA method for respiratory tract tumor stenoses recanalization is an effective, simple to implement and can be used in patients with severe comorbidities. Keyword: endoscopic operations, lung cancer, palliative treatment Background: CNS metastases are known complications of advanced EGFR mutation-positive NSCLC, thus, LUX-Lung (LL) trials investigating afatinib allowed enrolment of patients with brain metastases (BM). LL3, 6 and 7 previously demonstrated activity of afatinib in patients with BM, with the magnitude of progression-free survival (PFS) improv...
Background: Globally, gastric cancer (GC) ranks as the third cause of cancer related mortality. Like most malignancies, GC is characterized by its heterogeneity. In Chile, GC is the leading cause of cancer death claiming >3,000 deaths/year. Given its high heterogeneity an effective GC patient stratification may improve clinical outcomes. Here, we describe the results of the Chilean Gastric Cancer Task Force (GCTF) a descriptive cross sectional study (ClinicalTrials.gov identifier: NCT03158571, registered May 18, 2017) reporting clinical, genomic and protein expression data in a cohort of 224 patients. Methods: Demographic and basic information was obtained from 224 Chilean patients. We assessed p53, p16, HER2, and PDL1 expression and markers of Microsatellite Instability (MSI) by Tissue Microarray (TMA). We also assessed Epstein Barr Virus (EBV) status in a subset of 90 patients. Using Next Generation Sequencing (NGS), we profiled 143 cancer-related genes in a subset of 116 patients. Results: Patients were predominantly male (63.4%) staged III/IV (39.3 and 21.9%, respectively). Tumors were preferentially located at the stomach body (38.4%). Median overall survival (OS) was 39.0 months. By TMA analysis, 26.7% of patients were PDL1+, 13.3% were EBV+, and 13.3% MSI+. 36.7% were p16+, 13.3% HER2+3 and 56% possessed p53 overexpression. NGS confirmed TP53 as the most frequently mutated gene, followed by PI3KCA, VHL, PTEN and KRAS, together with alterations in numerous other actionable genes. Conclusions. Our data in Chilean GC patients demonstrate EBV+ is present at a higher proportion than reported in other geographical regions. In line with the published literature in South America, most patients were males staged III/IV. As anticipated, molecular analysis confirmed p53 as the most frequently altered gene in our cohort. A high number of further genomic alterations within actionable genes may allow the use of precision medicine within the Chilean population. Citation Format: Mauricio P. Pinto, Ignacio N. Retamal, Maria Loreto Bravo, Matias Muñoz-Medel, Miguel Cordova-Delgado, Diego Romero, Maria Jose Maturana, Nathaly De La Jara, Javiera Torres, Manuel Espinoza, Carlos Balmaceda, Matias Freire, Valentina Garate-Calderon, Javier Caceres-Molina, Gonzalo Sepulveda-Hermosilla, Rodrigo Lizana, Liliana Ramos, Fernando Crovari, Ricardo Armisen, Alejandro Corvalan, Gareth I. Owen, Marcelo Garrido. The Chilean gastric cancer task force: Final report [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3102.
Este artigo apresenta em detalhes a avaliação do sistema web miRQuest (http://mirquest.integrativebioinformatics.me/) que foi implementado e fez a integração dos principais preditores de microRNAs (miRNAs) em uma arquitetura de middleware, aplicado em um estudo com de caso em bioinformática.
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