Search results for: integrative bioinformatics
144 LncRNA NEAT1 Promotes NSCLC Progression through Acting as a ceRNA of miR-377-3p
Authors: Chengcao Sun, Shujun Li, Cuili Yang, Yongyong Xi, Liang Wang, Feng Zhang, Dejia Li
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Recently, the long non-coding RNA (lncRNA) NEAT1 has been identified as an oncogenic gene in multiple cancer types and elevated expression of NEAT1 was tightly linked to tumorigenesis and cancer progression. However, the molecular basis for this observation has not been characterized in progression of non-small cell lung cancer (NSCLC). In our studies, we identified NEAT1 was highly expressed in NSCLC patients and was a novel regulator of NSCLC progression. Patients whose tumors had high NEAT1 expression had a shorter overall survival than patients whose tumors had low NEAT1 expression. Further, NEAT1 significantly accelerates NSCLC cell growth and metastasis in vitro and tumor growth in vivo. Additionally, by using bioinformatics study and RNA pull down combined with luciferase reporter assays, we demonstrated that NEAT1 functioned as a competing endogenous RNA (ceRNA) for has-miR-377-3p, antagonized its functions and led to the de-repression of its endogenous targets E2F3, which was a core oncogene in promoting NSCLC progression. Taken together, these observations imply that the NEAT1 modulated the expression of E2F3 gene by acting as a competing endogenous RNA, which may build up the missing link between the regulatory miRNA network and NSCLC progression.Keywords: long non-coding RNA NEAT1, hsa-miRNA-377-3p, E2F3, non-small cell lung cancer, tumorigenesis
Procedia PDF Downloads 369143 Methodical Approach for the Integration of a Digital Factory Twin into the Industry 4.0 Processes
Authors: R. Hellmuth
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The orientation of flexibility and adaptability with regard to factory planning is at machine and process level. Factory buildings are not the focus of current research. Factory planning has the task of designing products, plants, processes, organization, areas and the construction of a factory. The adaptability of a factory can be divided into three types: spatial, organizational and technical adaptability. Spatial adaptability indicates the ability to expand and reduce the size of a factory. Here, the area-related breathing capacity plays the essential role. It mainly concerns the factory site, the plant layout and the production layout. The organizational ability to change enables the change and adaptation of organizational structures and processes. This includes structural and process organization as well as logistical processes and principles. New and reconfigurable operating resources, processes and factory buildings are referred to as technical adaptability. These three types of adaptability can be regarded independently of each other as undirected potentials of different characteristics. If there is a need for change, the types of changeability in the change process are combined to form a directed, complementary variable that makes change possible. When planning adaptability, importance must be attached to a balance between the types of adaptability. The vision of the intelligent factory building and the 'Internet of Things' presupposes the comprehensive digitalization of the spatial and technical environment. Through connectivity, the factory building must be empowered to support a company's value creation process by providing media such as light, electricity, heat, refrigeration, etc. In the future, communication with the surrounding factory building will take place on a digital or automated basis. In the area of industry 4.0, the function of the building envelope belongs to secondary or even tertiary processes, but these processes must also be included in the communication cycle. An integrative view of a continuous communication of primary, secondary and tertiary processes is currently not yet available and is being developed with the aid of methods in this research work. A comparison of the digital twin from the point of view of production and the factory building will be developed. Subsequently, a tool will be elaborated to classify digital twins from the perspective of data, degree of visualization, and the trades. Thus a contribution is made to better integrate the secondary and tertiary processes in a factory into the added value.Keywords: adaptability, digital factory twin, factory planning, industry 4.0
Procedia PDF Downloads 156142 Decellularized Brain-Chitosan Scaffold for Neural Tissue Engineering
Authors: Yun-An Chen, Hung-Jun Lin, Tai-Horng Young, Der-Zen Liu
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Decellularized brain extracellular matrix had been shown that it has the ability to influence on cell proliferation, differentiation and associated cell phenotype. However, this scaffold is thought to have poor mechanical properties and rapid degradation, it is hard for cell recellularization. In this study, we used decellularized brain extracellular matrix combined with chitosan, which is naturally occurring polysaccharide and non-cytotoxic polymer, forming a 3-D scaffold for neural stem/precursor cells (NSPCs) regeneration. HE staining and DAPI fluorescence staining confirmed decellularized process could effectively vanish the cellular components from the brain. GAGs and collagen I, collagen IV were be showed a great preservation by Alcain staining and immunofluorescence staining respectively. Decellularized brain extracellular matrix was well mixed in chitosan to form a 3-D scaffold (DB-C scaffold). The pore size was approximately 50±10 μm examined by SEM images. Alamar blue results demonstrated NSPCs had great proliferation ability in DB-C scaffold. NSPCs that were cultured in this complex scaffold differentiated into neurons and astrocytes, as reveled by NSPCs expression of microtubule-associated protein 2 (MAP2) and glial fibrillary acidic protein (GFAP). In conclusion, DB-C scaffold may provide bioinformatics cues for NSPCs generation and aid for CNS injury functional recovery applications.Keywords: brain, decellularization, chitosan, scaffold, neural stem/precursor cells
Procedia PDF Downloads 320141 Spatial Structure of First-Order Voronoi for the Future of Roundabout Cairo Since 1867
Authors: Ali Essam El Shazly
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The Haussmannization plan of Cairo in 1867 formed a regular network of roundabout spaces, though deteriorated at present. The method of identifying the spatial structure of roundabout Cairo for conservation matches the voronoi diagram with the space syntax through their geometrical property of spatial convexity. In this initiative, the primary convex hull of first-order voronoi adopts the integral and control measurements of space syntax on Cairo’s roundabout generators. The functional essence of royal palaces optimizes the roundabout structure in terms of spatial measurements and the symbolic voronoi projection of 'Tahrir Roundabout' over the Giza Nile and Pyramids. Some roundabouts of major public and commercial landmarks surround the pole of 'Ezbekia Garden' with a higher control than integral measurements, which filter the new spatial structure from the adjacent traditional town. Nevertheless, the least integral and control measures correspond to the voronoi contents of pollutant workshops and the plateau of old Cairo Citadel with the visual compensation of new royal landmarks on top. Meanwhile, the extended suburbs of infinite voronoi polygons arrange high control generators of chateaux housing in 'garden city' environs. The point pattern of roundabouts determines the geometrical characteristics of voronoi polygons. The measured lengths of voronoi edges alternate between the zoned short range at the new poles of Cairo and the distributed structure of longer range. Nevertheless, the shortest range of generator-vertex geometry concentrates at 'Ezbekia Garden' where the crossways of vast Cairo intersect, which maximizes the variety of choice at different spatial resolutions. However, the symbolic 'Hippodrome' which is the largest public landmark forms exclusive geometrical measurements, while structuring a most integrative roundabout to parallel the royal syntax. Overview of the symbolic convex hull of voronoi with space syntax interconnects Parisian Cairo with the spatial chronology of scattered monuments to conceive one universal Cairo structure. Accordingly, the approached methodology of 'voronoi-syntax' prospects the future conservation of roundabout Cairo at the inferred city-level concept.Keywords: roundabout Cairo, first-order Voronoi, space syntax, spatial structure
Procedia PDF Downloads 501140 Genome-Wide Isoform Specific KDM5A/JARID1A/RBP2 Location Analysis Reveals Contribution of Chromatin-Interacting PHD Domain in Protein Recruitment to Binding Sites
Authors: Abul B. M. M. K. Islam, Nuria Lopez-Bigas, Elizaveta V. Benevolenskaya
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RBP2 has shown to be important for cell differentiation control through epigenetic mechanism. The main aim of the present study is genome-wide location analysis of human RBP2 isoforms that differ in a histone-binding domain by ChIPseq. It is conceivable that the larger isoform (LI) of RBP2, which contains a specific H3K4me3 interacting domain, differs from the smaller isoform (SI) in genomic location, may account for the observed diversity in RBP2 function. To distinguish the two RBP2 isoforms, we used the fact that the SI lacks the C-terminal PHD domain and hence used the antibodies detecting both RBP2 isoforms (AI) through a common central domain, and the antibodies detecting only LI but not SI, through a C-terminal PHD domain. Overall our analysis suggests that RBP2 occupies about 77 nucleotides and binds GC rich motifs of active genes, does not bind to centromere, telomere, or enhancer regions, and binding sites are conserved compare to random. A striking difference between the only-SI and only-LI is that a large number of only-SI peaks are located in CpG islands and close to TSS compared to only-LI peaks. Enrichment analysis of the related genes indicates that several oncogenic pathways and metabolic pathways/processes are significantly enriched among only-SI/AI targets, but not LI/only-LI peak’s targets.Keywords: bioinformatics, cancer, ChIP-seq, KDM5A
Procedia PDF Downloads 307139 Gene Prediction in DNA Sequences Using an Ensemble Algorithm Based on Goertzel Algorithm and Anti-Notch Filter
Authors: Hamidreza Saberkari, Mousa Shamsi, Hossein Ahmadi, Saeed Vaali, , MohammadHossein Sedaaghi
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In the recent years, using signal processing tools for accurate identification of the protein coding regions has become a challenge in bioinformatics. Most of the genomic signal processing methods is based on the period-3 characteristics of the nucleoids in DNA strands and consequently, spectral analysis is applied to the numerical sequences of DNA to find the location of periodical components. In this paper, a novel ensemble algorithm for gene selection in DNA sequences has been presented which is based on the combination of Goertzel algorithm and anti-notch filter (ANF). The proposed algorithm has many advantages when compared to other conventional methods. Firstly, it leads to identify the coding protein regions more accurate due to using the Goertzel algorithm which is tuned at the desired frequency. Secondly, faster detection time is achieved. The proposed algorithm is applied on several genes, including genes available in databases BG570 and HMR195 and their results are compared to other methods based on the nucleotide level evaluation criteria. Implementation results show the excellent performance of the proposed algorithm in identifying protein coding regions, specifically in identification of small-scale gene areas.Keywords: protein coding regions, period-3, anti-notch filter, Goertzel algorithm
Procedia PDF Downloads 387138 Sorghum Resilience and Sustainability under Limiting and Non-limiting Conditions of Water and Nitrogen
Authors: Muhammad Tanveer Altaf, Mehmet Bedir, Waqas Liaqat, Gönül Cömertpay, Volkan Çatalkaya, Celaluddin Barutçular, Nergiz Çoban, Ibrahim Cerit, Muhammad Azhar Nadeem, Tolga Karaköy, Faheem Shehzad Baloch
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Food production needs to be almost double by 2050 in order to feed around 9 billion people around the Globe. Plant production mostly relies on fertilizers, which also have one of the main roles in environmental pollution. In addition to this, climatic conditions are unpredictable, and the earth is expected to face severe drought conditions in the future. Therefore, water and fertilizers, especially nitrogen are considered as main constraints for future food security. To face these challenges, developing integrative approaches for germplasm characterization and selecting the resilient genotypes performing under limiting conditions is very crucial for effective breeding to meet the food requirement under climatic change scenarios. This study is part of the European Research Area Network (ERANET) project for the characterization of the diversity panel of 172 sorghum accessions and six hybrids as control cultivars under limiting (+N/-H2O, -N/+H2O) and non-limiting conditions (+N+H2O). This study was planned to characterize the sorghum diversity in relation to resource Use Efficiency (RUE), with special attention on harnessing the interaction between genotype and environment (GxE) from a physiological and agronomic perspective. Experiments were conducted at Adana, a Mediterranean climate, with augmented design, and data on various agronomic and physiological parameters were recorded. Plentiful diversity was observed in the sorghum diversity panel and significant variations were seen among the limiting water and nitrogen conditions in comparison with the control experiment. Potential genotypes with the best performance are identified under limiting conditions. Whole genome resequencing was performed for whole germplasm under investigation for diversity analysis. GWAS analysis will be performed using genotypic and phenotypic data and linked markers will be identified. The results of this study will show the adaptation and improvement of sorghum under climate change conditions for future food security.Keywords: germplasm, sorghum, drought, nitrogen, resources use efficiency, sequencing
Procedia PDF Downloads 77137 Is there Anything Useful in That? High Value Product Extraction from Artemisia annua L. in the Spent Leaf and Waste Streams
Authors: Anike Akinrinlade
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The world population is estimated to grow from 7.1 billion to 9.22 billion by 2075, increasing therefore by 23% from the current global population. Much of the demographic changes up to 2075 will take place in the less developed regions. There are currently 54 countries which fall under the bracket of being defined as having ‘low-middle income’ economies and need new ways to generate valuable products from current resources that is available. Artemisia annua L is well used for the extraction of the phytochemical artemisinin, which accounts for around 0.01 to 1.4 % dry weight of the plant. Artemisinin is used in the treatment of malaria, a disease rampart in sub-Saharan Africa and in many other countries. Once artemisinin has been extracted the spent leaf and waste streams are disposed of as waste. A feasibility study was carried out looking at increasing the biomass value of A. annua, by designing a biorefinery where spent leaf and waste streams are utilized for high product generation. Quercetin, ferulic acid, dihydroartemisinic acid, artemisinic acid and artemsinin were screened for in the waste stream samples and the spent leaf. The analytical results showed that artemisinin, artemisinic acid and dihydroartemisinic acid were present in the waste extracts as well as camphor and arteannuin b. Ongoing effects are looking at using more industrially relevant solvents to extract the phytochemicals from the waste fractions and investigate how microwave pyrolysis of spent leaf can be utilized to generate bio-products.Keywords: high value product generation, bioinformatics, biomedicine, waste streams, spent leaf
Procedia PDF Downloads 349136 Using Biofunctool® Index to Assess Soil Quality after Eight Years of Conservation Agriculture in New Caledonia
Authors: Remy Kulagowski, Tobias Sturm, Audrey Leopold, Aurelie Metay, Josephine Peigne, Alexis Thoumazeau, Alain Brauman, Bruno Fogliani, Florent Tivet
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A major challenge for agriculture is to enhance productivity while limiting the impact on the environment. Conservation agriculture (CA) is one strategy whereby both sustainability and productivity can be achieved by preserving and improving the soil quality. Soils provide and regulate a large number of ecosystem services (ES) such as agricultural productivity and climate change adaptation and mitigation. The aim of this study is to assess the impacts of contrasted CA crop management on soil functions for maize (Zea mays L.) cultivation in an eight years field experiment (2010-2018). The study included two CA practices: direct seeding in dead mulch (DM) and living mulch (LM), and conventional plough-based tillage (CT) practices on a fluvisol in New Caledonia (French Archipelago in the South Pacific). In 2018, soil quality of the cropping systems were evaluated with the Biofunctool® set of indicators, that consists in twelve integrative, in-field, and low-tech indicators assessing the biological, physical and chemical properties of soils. Main soil functions were evaluated including (i) carbon transformation, (ii) structure maintenance, and (iii) nutrient cycling in the ten first soil centimeters. The results showed significant higher score for soil structure maintenance (e.g., aggregate stability, water infiltration) and carbon transformation function (e.g., soil respiration, labile carbon) under CA in DM and LM when compared with CT. Score of carbon transformation index was higher in DM compared with LM. However, no significant effect of cropping systems was observed on nutrient cycling (i.e., nitrogen and phosphorus). In conclusion, the aggregated synthetic scores of soil multi-functions evaluated with Biofunctool® demonstrate that CA cropping systems lead to a better soil functioning. Further analysis of the results with agronomic performance of the soil-crop systems would allow to better understand the links between soil functioning and production ES of CA.Keywords: conservation agriculture, cropping systems, ecosystem services, soil functions
Procedia PDF Downloads 157135 Genome-Wide Identification of Genes Resistance to Nitric Oxide in Vibrio parahaemolyticus
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Food poison caused by consumption of contaminated food, especially seafood, is one of most serious public health threats worldwide. Vibrio parahaemolyticus is emerging bacterial pathogen and the leading cause of human gastroenteritis associated with food poison, especially in the southern coastal region of China. To successfully cause disease in host, bacterial pathogens need to overcome the host-derived stresses encountered during infection. One of the toxic chemical species elaborated by the host is nitric oxide (NO). NO is generated by acidified nitrite in the stomach and by enzymes of the inducible NO synthase (iNOS) in the host cell, and is toxic to bacteria. Bacterial pathogens have evolved some mechanisms to battle with this toxic stress. Such mechanisms include genes to sense NO produced from immune system and activate others to detoxify NO toxicity, and genes to repair the damage caused by toxic reactive nitrogen species (RNS) generated during NO toxic stress. However, little is known about the NO resistance in V. parahaemolyticus. In this study, a transposon coupled with next generation sequencing (Tn-seq) technology will be utilized to identify genes for NO resistance in V. parahaemolyticus. Our strategy will include construction the saturating transposon insertion library, transposon library challenging with NO, next generation sequencing (NGS), bioinformatics analysis and verification of the identified genes in vitro and in vivo.Keywords: vibrio parahaemolyticus, nitric oxide, tn-seq, virulence
Procedia PDF Downloads 264134 Artificial Intelligence in Ethiopian Universities: The Influence of Technological Readiness, Acceptance, Perceived Risk, and Trust on Implementation - An Integrative Research Approach
Authors: Merih Welay Welesilassie
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Understanding educators' readiness to incorporate AI tools into their teaching methods requires comprehensively examining the influencing factors. This understanding is crucial, given the potential of these technologies to personalise learning experiences, improve instructional effectiveness, and foster innovative pedagogical approaches. This study evaluated factors affecting teachers' adoption of AI tools in their English language instruction by extending the Technology Acceptance Model (TAM) to encompass digital readiness support, perceived risk, and trust. A cross-sectional quantitative survey was conducted with 128 English language teachers, supplemented by qualitative data collection from 15 English teachers. The structural mode analysis indicated that implementing AI tools in Ethiopian higher education was notably influenced by digital readiness support, perceived ease of use, perceived usefulness, perceived risk, and trust. Digital readiness support positively impacted perceived ease of use, usefulness, and trust while reducing safety and privacy risks. Perceived ease of use positively correlated with perceived usefulness but negatively influenced trust. Furthermore, perceived usefulness strengthened trust in AI tools, while perceived safety and privacy risks significantly undermined trust. Trust was crucial in increasing educators' willingness to adopt AI technologies. The qualitative analysis revealed that the teachers exhibited strong content and pedagogical knowledge but needed more technology-related knowledge. Moreover, It was found that the teachers did not utilise digital tools to teach English. The study identified several obstacles to incorporating digital tools into English lessons, such as insufficient digital infrastructure, a shortage of educational resources, inadequate professional development opportunities, and challenging policies and governance. The findings provide valuable guidance for educators, inform policymakers about creating supportive digital environments, and offer a foundation for further investigation into technology adoption in educational settings in Ethiopia and similar contexts.Keywords: digital readiness support, AI acceptance, risk, trust
Procedia PDF Downloads 15133 Multi-Omics Integrative Analysis Coupled to Control Theory and Computational Simulation of a Genome-Scale Metabolic Model Reveal Controlling Biological Switches in Human Astrocytes under Palmitic Acid-Induced Lipotoxicity
Authors: Janneth Gonzalez, Andrés Pinzon Velasco, Maria Angarita
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Astrocytes play an important role in various processes in the brain, including pathological conditions such as neurodegenerative diseases. Recent studies have shown that the increase in saturated fatty acids such as palmitic acid (PA) triggers pro-inflammatorypathways in the brain. The use of synthetic neurosteroids such as tibolone has demonstrated neuro-protective mechanisms. However, broad studies with a systemic point of view on the neurodegenerative role of PA and the neuro-protective mechanisms of tibolone are lacking. In this study, we performed the integration of multi-omic data (transcriptome and proteome) into a human astrocyte genomic scale metabolic model to study the astrocytic response during palmitate treatment. We evaluated metabolic fluxes in three scenarios (healthy, induced inflammation by PA, and tibolone treatment under PA inflammation). We also applied a control theory approach to identify those reactions that exert more control in the astrocytic system. Our results suggest that PA generates a modulation of central and secondary metabolism, showing a switch in energy source use through inhibition of folate cycle and fatty acid β‐oxidation and upregulation of ketone bodies formation. We found 25 metabolic switches under PA‐mediated cellular regulation, 9 of which were critical only in the inflammatory scenario but not in the protective tibolone one. Within these reactions, inhibitory, total, and directional coupling profiles were key findings, playing a fundamental role in the (de)regulation of metabolic pathways that may increase neurotoxicity and represent potential treatment targets. Finally, the overall framework of our approach facilitates the understanding of complex metabolic regulation, and it can be used for in silico exploration of the mechanisms of astrocytic cell regulation, directing a more complex future experimental work in neurodegenerative diseases.Keywords: astrocytes, data integration, palmitic acid, computational model, multi-omics
Procedia PDF Downloads 97132 Development and Validation of an Instrument Measuring the Coping Strategies in Situations of Stress
Authors: Lucie Côté, Martin Lauzier, Guy Beauchamp, France Guertin
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Stress causes deleterious effects to the physical, psychological and organizational levels, which highlight the need to use effective coping strategies to deal with it. Several coping models exist, but they don’t integrate the different strategies in a coherent way nor do they take into account the new research on the emotional coping and acceptance of the stressful situation. To fill these gaps, an integrative model incorporating the main coping strategies was developed. This model arises from the review of the scientific literature on coping and from a qualitative study carried out among workers with low or high levels of stress, as well as from an analysis of clinical cases. The model allows one to understand under what circumstances the strategies are effective or ineffective and to learn how one might use them more wisely. It includes Specific Strategies in controllable situations (the Modification of the Situation and the Resignation-Disempowerment), Specific Strategies in non-controllable situations (Acceptance and Stubborn Relentlessness) as well as so-called General Strategies (Wellbeing and Avoidance). This study is intended to undertake and present the process of development and validation of an instrument to measure coping strategies based on this model. An initial pool of items has been generated from the conceptual definitions and three expert judges have validated the content. Of these, 18 items have been selected for a short form questionnaire. A sample of 300 students and employees from a Quebec university was used for the validation of the questionnaire. Concerning the reliability of the instrument, the indices observed following the inter-rater agreement (Krippendorff’s alpha) and the calculation of the coefficients for internal consistency (Cronbach's alpha) are satisfactory. To evaluate the construct validity, a confirmatory factor analysis using MPlus supports the existence of a model with six factors. The results of this analysis suggest also that this configuration is superior to other alternative models. The correlations show that the factors are only loosely related to each other. Overall, the analyses carried out suggest that the instrument has good psychometric qualities and demonstrates the relevance of further work to establish predictive validity and reconfirm its structure. This instrument will help researchers and clinicians better understand and assess coping strategies to cope with stress and thus prevent mental health issues.Keywords: acceptance, coping strategies, stress, validation process
Procedia PDF Downloads 339131 Greek Teachers' Understandings of Typical Language Development and of Language Difficulties in Primary School Children and Their Approaches to Language Teaching
Authors: Konstantina Georgali
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The present study explores Greek teachers’ understandings of typical language development and of language difficulties. Its core aim was to highlight that teachers need to have a thorough understanding of educational linguistics, that is of how language figures in education. They should also be aware of how language should be taught so as to promote language development for all students while at the same time support the needs of children with language difficulties in an inclusive ethos. The study, thus argued that language can be a dynamic learning mechanism in the minds of all children and a powerful teaching tool in the hands of teachers and provided current research evidence to show that structural and morphological particularities of native languages- in this case, of the Greek language- can be used by teachers to enhance children’s understanding of language and simultaneously improve oral language skills for children with typical language development and for those with language difficulties. The research was based on a Sequential Exploratory Mixed Methods Design deployed in three consecutive and integrative phases. The first phase involved 18 exploratory interviews with teachers. Its findings informed the second phase involving a questionnaire survey with 119 respondents. Contradictory questionnaire results were further investigated in a third phase employing a formal testing procedure with 60 children attending Y1, Y2 and Y3 of primary school (a research group of 30 language impaired children and a comparison group of 30 children with typical language development, both identified by their class teachers). Results showed both strengths and weaknesses in teachers’ awareness of educational linguistics and of language difficulties. They also provided a different perspective of children’s language needs and of language teaching approaches that reflected current advances and conceptualizations of language problems and opened a new window on how best they can be met in an inclusive ethos. However, teachers barely used teaching approaches that could capitalize on the particularities of the Greek language to improve language skills for all students in class. Although they seemed to realize the importance of oral language skills and their knowledge base on language related issues was adequate, their practices indicated that they did not see language as a dynamic teaching and learning mechanism that can promote children’s language development and in tandem, improve academic attainment. Important educational implications arose and clear indications of the generalization of findings beyond the Greek educational context.Keywords: educational linguistics, inclusive ethos, language difficulties, typical language development
Procedia PDF Downloads 382130 Classification of Multiple Cancer Types with Deep Convolutional Neural Network
Authors: Nan Deng, Zhenqiu Liu
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Thousands of patients with metastatic tumors were diagnosed with cancers of unknown primary sites each year. The inability to identify the primary cancer site may lead to inappropriate treatment and unexpected prognosis. Nowadays, a large amount of genomics and transcriptomics cancer data has been generated by next-generation sequencing (NGS) technologies, and The Cancer Genome Atlas (TCGA) database has accrued thousands of human cancer tumors and healthy controls, which provides an abundance of resource to differentiate cancer types. Meanwhile, deep convolutional neural networks (CNNs) have shown high accuracy on classification among a large number of image object categories. Here, we utilize 25 cancer primary tumors and 3 normal tissues from TCGA and convert their RNA-Seq gene expression profiling to color images; train, validate and test a CNN classifier directly from these images. The performance result shows that our CNN classifier can archive >80% test accuracy on most of the tumors and normal tissues. Since the gene expression pattern of distant metastases is similar to their primary tumors, the CNN classifier may provide a potential computational strategy on identifying the unknown primary origin of metastatic cancer in order to plan appropriate treatment for patients.Keywords: bioinformatics, cancer, convolutional neural network, deep leaning, gene expression pattern
Procedia PDF Downloads 299129 A Local Tensor Clustering Algorithm to Annotate Uncharacterized Genes with Many Biological Networks
Authors: Paul Shize Li, Frank Alber
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A fundamental task of clinical genomics is to unravel the functions of genes and their associations with disorders. Although experimental biology has made efforts to discover and elucidate the molecular mechanisms of individual genes in the past decades, still about 40% of human genes have unknown functions, not to mention the diseases they may be related to. For those biologists who are interested in a particular gene with unknown functions, a powerful computational method tailored for inferring the functions and disease relevance of uncharacterized genes is strongly needed. Studies have shown that genes strongly linked to each other in multiple biological networks are more likely to have similar functions. This indicates that the densely connected subgraphs in multiple biological networks are useful in the functional and phenotypic annotation of uncharacterized genes. Therefore, in this work, we have developed an integrative network approach to identify the frequent local clusters, which are defined as those densely connected subgraphs that frequently occur in multiple biological networks and consist of the query gene that has few or no disease or function annotations. This is a local clustering algorithm that models multiple biological networks sharing the same gene set as a three-dimensional matrix, the so-called tensor, and employs the tensor-based optimization method to efficiently find the frequent local clusters. Specifically, massive public gene expression data sets that comprehensively cover dynamic, physiological, and environmental conditions are used to generate hundreds of gene co-expression networks. By integrating these gene co-expression networks, for a given uncharacterized gene that is of biologist’s interest, the proposed method can be applied to identify the frequent local clusters that consist of this uncharacterized gene. Finally, those frequent local clusters are used for function and disease annotation of this uncharacterized gene. This local tensor clustering algorithm outperformed the competing tensor-based algorithm in both module discovery and running time. We also demonstrated the use of the proposed method on real data of hundreds of gene co-expression data and showed that it can comprehensively characterize the query gene. Therefore, this study provides a new tool for annotating the uncharacterized genes and has great potential to assist clinical genomic diagnostics.Keywords: local tensor clustering, query gene, gene co-expression network, gene annotation
Procedia PDF Downloads 168128 Analysis of Osmotin as Transcription Factor/Cell Signaling Modulator Using Bioinformatic Tools
Authors: Usha Kiran, M. Z. Abdin
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Osmotin is an abundant cationic multifunctional protein discovered in cells of tobacco (Nicotiana tabacum L. var Wisconsin 38) adapted to an environment of low osmotic potential. It provides plants protection from pathogens, hence placed in the PRP family of proteins. The osmotin induced proline accumulation has been reported in plants including transgenic tomato and strawberry conferring tolerance against both biotic and abiotic stresses. The exact mechanism of induction of proline by osmotin is however, not known till date. These observations have led us to hypothesize that osmotin induced proline accumulation could be due to its involvement as transcription factor and/or cell signal pathway modulator in proline biosynthesis. The present investigation was therefore, undertaken to analyze the osmotin protein as transcription factor /cell signalling modulator using bioinformatics tools. The results of available online DNA binding motif search programs revealed that osmotin does not contain DNA-binding motifs. The alignment results of osmotin protein with the protein sequence from DATF showed the homology in the range of 0-20%, suggesting that it might not contain a DNA binding motif. Further to find unique DNA-binding domain, the superimposition of osmotin 3D structure on modeled Arabidopsis transcription factors using Chimera also suggested absence of the same. We, however, found evidence implicating osmotin in cell signaling. With these results, we concluded that osmotin is not a transcription factor but regulating proline biosynthesis and accumulation through cell signaling during abiotic stresses.Keywords: osmotin, cell signaling modulator, bioinformatic tools, protein
Procedia PDF Downloads 272127 Computational Approach for Grp78–Nf-ΚB Binding Interactions in the Context of Neuroprotective Pathway in Brain Injuries
Authors: Janneth Gonzalez, Marco Avila, George Barreto
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GRP78 participates in multiple functions in the cell during normal and pathological conditions, controlling calcium homeostasis, protein folding and unfolded protein response. GRP78 is located in the endoplasmic reticulum, but it can change its location under stress, hypoxic and apoptotic conditions. NF-κB represents the keystone of the inflammatory process and regulates the transcription of several genes related with apoptosis, differentiation, and cell growth. The possible relationship between GRP78-NF-κB could support and explain several mechanisms that may regulate a variety of cell functions, especially following brain injuries. Although several reports show interactions between NF-κB and heat shock proteins family members, there is a lack of information on how GRP78 may be interacting with NF-κB, and possibly regulating its downstream activation. Therefore, we assessed the computational predictions of the GRP78 (Chain A) and NF-κB complex (IkB alpha and p65) protein-protein interactions. The interaction interface of the docking model showed that the amino acids ASN 47, GLU 215, GLY 403 of GRP78 and THR 54, ASN 182 and HIS 184 of NF-κB are key residues involved in the docking. The electrostatic field between GRP78-NF-κB interfaces and molecular dynamic simulations support the possible interaction between the proteins. In conclusion, this work shed some light in the possible GRP78-NF-κB complex indicating key residues in this crosstalk, which may be used as an input for better drug design strategy targeting NF-κB downstream signaling as a new therapeutic approach following brain injuries.Keywords: computational biology, protein interactions, Grp78, bioinformatics, molecular dynamics
Procedia PDF Downloads 342126 Glycan Analyzer: Software to Annotate Glycan Structures from Exoglycosidase Experiments
Authors: Ian Walsh, Terry Nguyen-Khuong, Christopher H. Taron, Pauline M. Rudd
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Glycoproteins and their covalently bonded glycans play critical roles in the immune system, cell communication, disease and disease prognosis. Ultra performance liquid chromatography (UPLC) coupled with mass spectrometry is conventionally used to qualitatively and quantitatively characterise glycan structures in a given sample. Exoglycosidases are enzymes that catalyze sequential removal of monosaccharides from the non-reducing end of glycans. They naturally have specificity for a particular type of sugar, its stereochemistry (α or β anomer) and its position of attachment to an adjacent sugar on the glycan. Thus, monitoring the peak movements (both in the UPLC and MS1) after application of exoglycosidases provides a unique and effective way to annotate sugars with high detail - i.e. differentiating positional and linkage isomers. Manual annotation of an exoglycosidase experiment is difficult and time consuming. As such, with increasing sample complexity and the number of exoglycosidases, the analysis could result in manually interpreting hundreds of peak movements. Recently, we have implemented pattern recognition software for automated interpretation of UPLC-MS1 exoglycosidase digestions. In this work, we explain the software, indicate how much time it will save and provide example usage showing the annotation of positional and linkage isomers in Immunoglobulin G, apolipoprotein J, and simple glycan standards.Keywords: bioinformatics, automated glycan assignment, liquid chromatography, mass spectrometry
Procedia PDF Downloads 200125 Contestation and Coexistence: An Exploratory Study of the Interactions between Formal and Informal Sectors within eThekwini City Centre
Authors: Mulaudzi Tshimbiluni Annah
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South African city centres depict dynamic urban spaces which reflect complex interactions between multiple actors: the state, formal businesses and informal street traders, with each competing for territorial claims and spatial dominance. The objective of the study is exploring how space is contested, negotiated and occupied between formal and informal sectors, while consequently trying to understand the implication that this has on spatial planning and spatial justice. Through a case-study analysis of the eThekwini city centre, this research examines spatial arrangement, coexistence and conflicts that shape the urban fabric. The study employs spatial justice as a theoretical lens to highlight the inequalities that are embedded within urban planning policies and how street traders are resilient to the harsh restrictive spatial frameworks. Limited evidence is known about how urban planning frameworks can integrate informal street traders in city centres and recognize them as legitimate stakeholders. The study investigates how spatial planning frameworks can be reimagined to promote spatial justice and further facilitate coexistence between formal and informal stakeholders in city centres. Primary data collection included interviews with key stakeholders, while NVivo software was used to analyse the interview data. Observations were conducted through transect walks, which allowed for insight into the spatial dynamics and daily interactions. Visual representations were depicted using GIS mapping to show areas of contestation as well as areas where formal and informal activities intersect. Furthermore, secondary data from literature enabled a comparative analysis of similar case studies through precedent studies. The study revealed continuous contestation by formal businesses and the state, who are for the most part often prioritized by planning frameworks while street traders are often marginalized regardless of their contribution towards economic development. This study therefore proposes strategies for spatial planning that supports an integrative urban framework which ensures equitable access and also a reduction of the marginalization of street traders within urban spaces. This study aims to contribute to understanding urban coexistence and further advocates for spatial planning approaches that integrates informal street traders as legitimate actors in the urban landscape while fostering spatial justice within city centres.Keywords: coexistence, contestation, integration, spatial justice, spatial planning, street traders
Procedia PDF Downloads 12124 Application of KL Divergence for Estimation of Each Metabolic Pathway Genes
Authors: Shohei Maruyama, Yasuo Matsuyama, Sachiyo Aburatani
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The development of the method to annotate unknown gene functions is an important task in bioinformatics. One of the approaches for the annotation is The identification of the metabolic pathway that genes are involved in. Gene expression data have been utilized for the identification, since gene expression data reflect various intracellular phenomena. However, it has been difficult to estimate the gene function with high accuracy. It is considered that the low accuracy of the estimation is caused by the difficulty of accurately measuring a gene expression. Even though they are measured under the same condition, the gene expressions will vary usually. In this study, we proposed a feature extraction method focusing on the variability of gene expressions to estimate the genes' metabolic pathway accurately. First, we estimated the distribution of each gene expression from replicate data. Next, we calculated the similarity between all gene pairs by KL divergence, which is a method for calculating the similarity between distributions. Finally, we utilized the similarity vectors as feature vectors and trained the multiclass SVM for identifying the genes' metabolic pathway. To evaluate our developed method, we applied the method to budding yeast and trained the multiclass SVM for identifying the seven metabolic pathways. As a result, the accuracy that calculated by our developed method was higher than the one that calculated from the raw gene expression data. Thus, our developed method combined with KL divergence is useful for identifying the genes' metabolic pathway.Keywords: metabolic pathways, gene expression data, microarray, Kullback–Leibler divergence, KL divergence, support vector machines, SVM, machine learning
Procedia PDF Downloads 403123 Understanding the Nature of Blood Pressure as Metabolic Syndrome Component in Children
Authors: Mustafa M. Donma, Orkide Donma
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Pediatric overweight and obesity need attention because they may cause morbid obesity, which may develop metabolic syndrome (MetS). Criteria used for the definition of adult MetS cannot be applied for pediatric MetS. Dynamic physiological changes that occur during childhood and adolescence require the evaluation of each parameter based upon age intervals. The aim of this study is to investigate the distribution of blood pressure (BP) values within diverse pediatric age intervals and the possible use and clinical utility of a recently introduced Diagnostic Obesity Notation Model Assessment Tension (DONMA tense) Index derived from systolic BP (SBP) and diastolic BP (DBP) [SBP+DBP/200]. Such a formula may enable a more integrative picture for the assessment of pediatric obesity and MetS due to the use of both SBP and DBP. 554 children, whose ages were between 6-16 years participated in the study; the study population was divided into two groups based upon their ages. The first group comprises 280 cases aged 6-10 years (72-120 months), while those aged 10-16 years (121-192 months) constituted the second group. The values of SBP, DBP and the formula (SBP+DBP/200) covering both were evaluated. Each group was divided into seven subgroups with varying degrees of obesity and MetS criteria. Two clinical definitions of MetS have been described. These groups were MetS3 (children with three major components), and MetS2 (children with two major components). The other groups were morbid obese (MO), obese (OB), overweight (OW), normal (N) and underweight (UW). The children were included into the groups according to the age- and sex-based body mass index (BMI) percentile values tabulated by WHO. Data were evaluated by SPSS version 16 with p < 0.05 as the statistical significance degree. Tension index was evaluated in the groups above and below 10 years of age. This index differed significantly between N and MetS as well as OW and MetS groups (p = 0.001) above 120 months. However, below 120 months, significant differences existed between MetS3 and MetS2 (p = 0.003) as well as MetS3 and MO (p = 0.001). In comparison with the SBP and DBP values, tension index values have enabled more clear-cut separation between the groups. It has been detected that the tension index was capable of discriminating MetS3 from MetS2 in the group, which was composed of children aged 6-10 years. This was not possible in the older group of children. This index was more informative for the first group. This study also confirmed that 130 mm Hg and 85 mm Hg cut-off points for SBP and DBP, respectively, are too high for serving as MetS criteria in children because the mean value for tension index was calculated as 1.00 among MetS children. This finding has shown that much lower cut-off points must be set for SBP and DBP for the diagnosis of pediatric MetS, especially for children under-10 years of age. This index may be recommended to discriminate MO, MetS2 and MetS3 among the 6-10 years of age group, whose MetS diagnosis is problematic.Keywords: blood pressure, children, index, metabolic syndrome, obesity
Procedia PDF Downloads 117122 “I” on the Web: Social Penetration Theory Revised
Authors: Dr. Dionysis Panos Dpt. Communication, Internet Studies Cyprus University of Technology
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The widespread use of New Media and particularly Social Media, through fixed or mobile devices, has changed in a staggering way our perception about what is “intimate" and "safe" and what is not, in interpersonal communication and social relationships. The distribution of self and identity-related information in communication now evolves under new and different conditions and contexts. Consequently, this new framework forces us to rethink processes and mechanisms, such as what "exposure" means in interpersonal communication contexts, how the distinction between the "private" and the "public" nature of information is being negotiated online, how the "audiences" we interact with are understood and constructed. Drawing from an interdisciplinary perspective that combines sociology, communication psychology, media theory, new media and social networks research, as well as from the empirical findings of a longitudinal comparative research, this work proposes an integrative model for comprehending mechanisms of personal information management in interpersonal communication, which can be applied to both types of online (Computer-Mediated) and offline (Face-To-Face) communication. The presentation is based on conclusions drawn from a longitudinal qualitative research study with 458 new media users from 24 countries for almost over a decade. Some of these main conclusions include: (1) There is a clear and evidenced shift in users’ perception about the degree of "security" and "familiarity" of the Web, between the pre- and the post- Web 2.0 era. The role of Social Media in this shift was catalytic. (2) Basic Web 2.0 applications changed dramatically the nature of the Internet itself, transforming it from a place reserved for “elite users / technical knowledge keepers" into a place of "open sociability” for anyone. (3) Web 2.0 and Social Media brought about a significant change in the concept of “audience” we address in interpersonal communication. The previous "general and unknown audience" of personal home pages, converted into an "individual & personal" audience chosen by the user under various criteria. (4) The way we negotiate the nature of 'private' and 'public' of the Personal Information, has changed in a fundamental way. (5) The different features of the mediated environment of online communication and the critical changes occurred since the Web 2.0 advance, lead to the need of reconsideration and updating the theoretical models and analysis tools we use in our effort to comprehend the mechanisms of interpersonal communication and personal information management. Therefore, is proposed here a new model for understanding the way interpersonal communication evolves, based on a revision of social penetration theory.Keywords: new media, interpersonal communication, social penetration theory, communication exposure, private information, public information
Procedia PDF Downloads 371121 Evaluation of Impact on Traffic Conditions Due to Electronic Toll Collection System Design in Thailand
Authors: Kankrong Suangka
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This research explored behaviors of toll way users that impact their decision to use the Electronic Toll Collection System (ETC). It also went on to explore and evaluated the efficiency of toll plaza in terms of number of ETC booths in toll plaza and its lane location. The two main parameters selected for the scenarios analyzed were (1) the varying ration of ETC enabled users (2) the varying locations of the dedicated ETC lane. There were a total of 42 scenarios analyzed. Researched data indicated that in A.D.2013, the percentage of ETC user from the total toll user is 22%. It was found that the delay at the payment booth was reduced by increasing the ETC booth by 1 more lane under the condition that the volume of ETC users passing through the plaza less than 1,200 vehicles/hour. Meanwhile, increasing the ETC lanes by 2 lanes can accommodate an increased traffic volume to around 1,200 to 1,800 vehicles/hour. Other than that, in terms of the location of ETC lane, it was found that if for one ETC lane-plazas, installing the ETC lane at the far right are the best alternative. For toll plazas with 2 ETC lanes, the best layout is to have 1 lane in the middle and 1 lane at the far right. This layout shows the least delay when compared to other layouts. Furthermore, the results from this research showed that micro-simulator traffic models have potential for further applications and use in designing toll plaza lanes. Other than that, the results can also be used to analyze the system of the nearby area with similar traffic volume and can be used for further design improvements.Keywords: the electronic toll collection system, average queuing delay, toll plaza configuration, bioinformatics, biomedicine
Procedia PDF Downloads 239120 Preventing the Septic Shock in an Oncological Patient with Febrile Neutropenia Submitted to Chemotherapy: The Nurse's Responsibility
Authors: Hugo Reis, Isabel Rabiais
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The main purpose of the present study is to understand the nurse’s responsibility in preventing the septic shock in an oncological patient with febrile neutropenia submitted to chemotherapy. In order to do it, an integrative review of literature has been conducted. In the research done in many databases, it was concluded that only 7 out of 5202 articles compiled the entire inclusion standard present in the strict protocol of research, being this made up by all different methodologies. On the research done in the 7 articles it has resulted 8 text macro-units associated to different nursing interventions: ‘Health Education’; ‘Prophylactic Therapy Administration’; ‘Scales Utilization’; ‘Patient Evaluation’; ‘Environment Control’; ‘Performance of Diagnostic Auxiliary Exams’; ‘Protocol Enforcement/Procedure Guidelines’; ‘Antibiotic Therapy Administration’. Concerning the prevalence/result’s division there can be identified many conclusions: the macro-units ‘Patient Evaluation’, ‘Performance of Diagnostic Auxiliary Exams’, and ‘Antibiotic Therapy Administration’ present themselves to be the most prevalent in the research – 6 in 7 occurrences (approximately 85.7%). Next, the macro-unit ‘Protocol Enforcement/Procedure Guidelines’ presents itself as an important expression unit – being part of 5 out of the 7 analyzed studies (approximately 71.4%). The macro-unit ‘Health Education’, seems to be in the same way, an important expression unit – 4 out of the 7 (or approximately 57%). The macro-unit ‘Scales Utilization’, represents a minor part in the research done – it’s in only 2 out of the 7 cases (approximately 28.6%). On the other hand, the macro-units ‘Prophylactic Therapy Administration’ and ‘Environment Control’ are the two categories with fewer results in the research - 1 out of the 7 cases, the same as approximately 14.3% of the research results. Every research done to the macro-unit ‘Antibiotic Therapy Administration’ agreed to refer that the intervention should be strictly done, in a period of time less than one hour after diagnosing the fever, with the purpose of controlling the quick spread of infection – minimizing its seriousness. Identifying these interventions contributes, concluding that, to adopt strategies in order to prevent the phenomenon that represents a daily scenario responsible for the cost´s increase in health institutions, being at the same time responsible for the high morbidity rates and mortality increase associated with this specific group of patients.Keywords: febrile neutropenia, oncology nursing, patient, septic shock
Procedia PDF Downloads 216119 Antibody Reactivity of Synthetic Peptides Belonging to Proteins Encoded by Genes Located in Mycobacterium tuberculosis-Specific Genomic Regions of Differences
Authors: Abu Salim Mustafa
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The comparisons of mycobacterial genomes have identified several Mycobacterium tuberculosis-specific genomic regions that are absent in other mycobacteria and are known as regions of differences. Due to M. tuberculosis-specificity, the peptides encoded by these regions could be useful in the specific diagnosis of tuberculosis. To explore this possibility, overlapping synthetic peptides corresponding to 39 proteins predicted to be encoded by genes present in regions of differences were tested for antibody-reactivity with sera from tuberculosis patients and healthy subjects. The results identified four immunodominant peptides corresponding to four different proteins, with three of the peptides showing significantly stronger antibody reactivity and rate of positivity with sera from tuberculosis patients than healthy subjects. The fourth peptide was recognized equally well by the sera of tuberculosis patients as well as healthy subjects. Predication of antibody epitopes by bioinformatics analyses using ABCpred server predicted multiple linear epitopes in each peptide. Furthermore, peptide sequence analysis for sequence identity using BLAST suggested M. tuberculosis-specificity for the three peptides that had preferential reactivity with sera from tuberculosis patients, but the peptide with equal reactivity with sera of TB patients and healthy subjects showed significant identity with sequences present in nob-tuberculous mycobacteria. The three identified M. tuberculosis-specific immunodominant peptides may be useful in the serological diagnosis of tuberculosis.Keywords: genomic regions of differences, Mycobacterium tuberculossis, peptides, serodiagnosis
Procedia PDF Downloads 183118 Non-Invasive Pre-Implantation Genetic Assessment Using NGS in IVF Clinical Routine
Authors: Katalin Gombos, Bence Gálik, Krisztina Ildikó Kalács, Krisztina Gödöny, Ákos Várnagy, József Bódis, Attila Gyenesei, Gábor L. Kovács
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Although non-invasive pre-implantation genetic testing for aneuploidy (NIPGT-A) is potentially appropriate to assess chromosomal ploidy of the embryo, practical application of it in a routine IVF center has not been started in the absence of a recommendation. We developed a comprehensive workflow for a clinically applicable strategy for NIPGT-A based on next-generation sequencing (NGS) technology. We performed MALBAC whole genome amplification and NGS on spent blastocyst culture media of Day 3 embryos fertilized with intra-cytoplasmic sperm injection (ICSI). Spent embryonic culture media of morphologically good quality score embryos were enrolled in further analysis with the blank culture media as background control. Chromosomal abnormalities were identified by an optimized bioinformatics pipeline applying a copy number variation (CNV) detecting algorithm. We demonstrate a comprehensive workflow covering both wet- and dry-lab procedures supporting a clinically applicable strategy for NIPGT-A. It can be carried out within 48 h which is critical for the same-cycle blastocyst transfer, but also suitable for “freeze all” and “elective frozen embryo” strategies. The described integrated approach of non-invasive evaluation of embryonic DNA content of the culture media can potentially supplement existing pre-implantation genetic screening methods.Keywords: next generation sequencing, in vitro fertilization, embryo assessment, non-invasive pre-implantation genetic testing
Procedia PDF Downloads 156117 Characterization of the Intestinal Microbiota: A Signature in Fecal Samples from Patients with Irritable Bowel Syndrome
Authors: Mina Hojat Ansari, Kamran Bagheri Lankarani, Mohammad Reza Fattahi, Ali Reza Safarpour
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Irritable bowel syndrome (IBS) is a common bowel disorder which is usually diagnosed through the abdominal pain, fecal irregularities and bloating. Alteration in the intestinal microbial composition is implicating to inflammatory and functional bowel disorders which is recently also noted as an IBS feature. Owing to the potential importance of microbiota implication in both efficiencies of the treatment and prevention of the diseases, we examined the association between the intestinal microbiota and different bowel patterns in a cohort of subjects with IBS and healthy controls. Fresh fecal samples were collected from a total of 50 subjects, 30 of whom met the Rome IV criteria for IBS and 20 Healthy control. Total DNA was extracted and library preparation was conducted following the standard protocol for small whole genome sequencing. The pooled libraries sequenced on an Illumina Nextseq platform with a 2 × 150 paired-end read length and obtained sequences were analyzed using several bioinformatics programs. The majority of sequences obtained in the current study assigned to bacteria. However, our finding highlighted the significant microbial taxa variation among the studied groups. The result, therefore, suggests a significant association of the microbiota with symptoms and bowel characteristics in patients with IBS. These alterations in fecal microbiota could be exploited as a biomarker for IBS or its subtypes and suggest the modification of the microbiota might be integrated into prevention and treatment strategies for IBS.Keywords: irritable bowel syndrome, intestinal microbiota, small whole genome sequencing, fecal samples, Illumina
Procedia PDF Downloads 166116 Genome Characterization and Phylogeny Analysis of Viruses Infected Invertebrates, Parvoviridae Family
Authors: Niloofar Fariborzi, Hamzeh Alipour, Kourosh Azizi, Neda Eskandarzade, Abozar Ghorbani
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The family Parvoviridae consists of a large diversity of single-stranded DNA viruses, which cause mild to severe diseases in both vertebrates and invertebrates. The Parvoviridae are classified into three subfamilies: Parvovirinae infect vertebrates, Densovirinae infects invertebrates, while Hamaparovirinae infects both vertebrates and invertebrates. Except for the NS1 region, which is the prime criterion for phylogeny analysis, other parts of the parvoviruses genome, such as UTRs, are diverse even among closely related viruses or within the same genus. It is believed that host switching in parvoviruses may be related to genetic changes in regions other than NS1; therefore, whole-genome screening is valuable for studying parvoviruses' host-virus interactions. The aim of this study was to analyze genome organization and phylogeny of the complete genome sequence of the 132 Paroviridae family members, focusing on viruses that infect invertebrates. The maximum and minimum divergence within each subfamily belonged to Densovirinae and Parvovirinae, respectively. The greatest evolutionary divergence was between Hamaparovirinae and Parvovirinae. Unclassified viruses were mostly from Parovirinae and had the highest divergence to densoviruses and the lowest divergence to Parovirinae viruses. In a phylogenetic tree, all hamparoviruses were found in the center of densoviruses, with the exception of Syngnathid Ichthamaparvovirus 1 (NC_055527), which was positioned between two Parvovirinae members (NC _022089 and NC_038544). The proximity of hamparoviruses members to some densoviruses strengthens the possibility that densoviruses may be the ancestors of hamaparoviruses or vice versa. Therefore, examination and phylogeny analysis of the whole genome is necessary to understand Parvoviridae family host selection.Keywords: densoviruses, parvoviridae, bioinformatics, phylogeny
Procedia PDF Downloads 93115 The Genetic Architecture Underlying Dilated Cardiomyopathy in Singaporeans
Authors: Feng Ji Mervin Goh, Edmund Chee Jian Pua, Stuart Alexander Cook
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Dilated cardiomyopathy (DCM) is a common cause of heart failure. Genetic mutations account for 50% of DCM cases with TTN mutations being the most common, accounting for up to 25% of DCM cases. However, the genetic architecture underlying Asian DCM patients is unknown. We evaluated 68 patients (female= 17) with DCM who underwent follow-up at the National Heart Centre, Singapore from 2013 through 2014. Clinical data were obtained and analyzed retrospectively. Genomic DNA was subjected to next-generation targeted sequencing. Nextera Rapid Capture Enrichment was used to capture the exons of a panel of 169 cardiac genes. DNA libraries were sequenced as paired-end 150-bp reads on Illumina MiSeq. Raw sequence reads were processed and analysed using standard bioinformatics techniques. The average age of onset of DCM was 46.1±10.21 years old. The average left ventricular ejection fraction (LVEF), left ventricular diastolic internal diameter (LVIDd), left ventricular systolic internal diameter (LVIDs) were 26.1±11.2%, 6.20±0.83cm, and 5.23±0.92cm respectively. The frequencies of mutations in major DCM-associated genes were as follows TTN (5.88% vs published frequency of 20%), LMNA (4.41% vs 6%), MYH7 (5.88% vs 4%), MYH6 (5.88% vs 4%), and SCN5a (4.41% vs 3%). The average callability at 10 times coverage of each major gene were: TTN (99.7%), LMNA (87.1%), MYH7 (94.8%), MYH6 (95.5%), and SCN5a (94.3%). In conclusion, TTN mutations are not common in Singaporean DCM patients. The frequencies of other major DCM-associated genes are comparable to frequencies published in the current literature.Keywords: heart failure, dilated cardiomyopathy, genetics, next-generation sequencing
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