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Artykuły w czasopismach na temat "INTEGRATIVE TRANSCRIPTOME"
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Rhodes, Daniel R., i Arul M. Chinnaiyan. "Integrative analysis of the cancer transcriptome". Nature Genetics 37, S6 (czerwiec 2005): S31—S37. http://dx.doi.org/10.1038/ng1570.
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Berger, M. F., J. Z. Levin, K. Vijayendran, A. Sivachenko, X. Adiconis, J. Maguire, L. A. Johnson i in. "Integrative analysis of the melanoma transcriptome". Genome Research 20, nr 4 (23.02.2010): 413–27. http://dx.doi.org/10.1101/gr.103697.109.
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Grausa, Kristina, Ivars Mozga, Karlis Pleiko i Agris Pentjuss. "Integrative Gene Expression and Metabolic Analysis Tool IgemRNA". Biomolecules 12, nr 4 (16.04.2022): 586. http://dx.doi.org/10.3390/biom12040586.
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Genome-scale metabolic modeling is widely used to study the impact of metabolism on the phenotype of different organisms. While substrate modeling reflects the potential distribution of carbon and other chemical elements within the model, the additional use of omics data, e.g., transcriptome, has implications when researching the genotype–phenotype responses to environmental changes. Several algorithms for transcriptome analysis using genome-scale metabolic modeling have been proposed. Still, they are restricted to specific objectives and conditions and lack flexibility, have software compatibility issues, and require advanced user skills. We classified previously published algorithms, summarized transcriptome pre-processing, integration, and analysis methods, and implemented them in the newly developed transcriptome analysis tool IgemRNA, which (1) has a user-friendly graphical interface, (2) tackles compatibility issues by combining previous data input and pre-processing algorithms in MATLAB, and (3) introduces novel algorithms for the automatic comparison of different transcriptome datasets with or without Cobra Toolbox 3.0 optimization algorithms. We used publicly available transcriptome datasets from Saccharomyces cerevisiae BY4741 and H4-S47D strains for validation. We found that IgemRNA provides a means for transcriptome and environmental data validation on biochemical network topology since the biomass function varies for different phenotypes. Our tool can detect problematic reaction constraints.
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Singh, Amar V., Kenneth B. Knudsen i Thomas B. Knudsen. "Integrative analysis of the mouse embryonic transcriptome". Bioinformation 1, nr 10 (10.04.2007): 406–13. http://dx.doi.org/10.6026/97320630001406.
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Sneha, Nela Pragathi, S. Akila Parvathy Dharshini, Y. H. Taguchi i M. Michael Gromiha. "Integrative Meta-Analysis of Huntington’s Disease Transcriptome Landscape". Genes 13, nr 12 (16.12.2022): 2385. http://dx.doi.org/10.3390/genes13122385.
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Huntington’s disease (HD) is a neurodegenerative disorder with autosomal dominant inheritance caused by glutamine expansion in the Huntingtin gene (HTT). Striatal projection neurons (SPNs) in HD are more vulnerable to cell death. The executive striatal population is directly connected with the Brodmann Area (BA9), which is mainly involved in motor functions. Analyzing the disease samples from BA9 from the SRA database provides insights related to neuron degeneration, which helps to identify a promising therapeutic strategy. Most gene expression studies examine the changes in expression and associated biological functions. In this study, we elucidate the relationship between variants and their effect on gene/downstream transcript expression. We computed gene and transcript abundance and identified variants from RNA-seq data using various pipelines. We predicted the effect of genome-wide association studies (GWAS)/novel variants on regulatory functions. We found that many variants affect the histone acetylation pattern in HD, thereby perturbing the transcription factor networks. Interestingly, some variants affect miRNA binding as well as their downstream gene expression. Tissue-specific network analysis showed that mitochondrial, neuroinflammation, vasculature, and angiogenesis-related genes are disrupted in HD. From this integrative omics analysis, we propose that abnormal neuroinflammation acts as a two-edged sword that indirectly affects the vasculature and associated energy metabolism. Rehabilitation of blood-brain barrier functionality and energy metabolism may secure the neuron from cell death.
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Morabito, Samuel, Emily Miyoshi, Neethu Michael i Vivek Swarup. "Integrative genomics approach identifies conserved transcriptomic networks in Alzheimer’s disease". Human Molecular Genetics 29, nr 17 (17.08.2020): 2899–919. http://dx.doi.org/10.1093/hmg/ddaa182.
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Abstract Alzheimer’s disease (AD) is a devastating neurological disorder characterized by changes in cell-type proportions and consequently marked alterations of the transcriptome. Here we use a data-driven systems biology meta-analytical approach across three human AD cohorts, encompassing six cortical brain regions, and integrate with multi-scale datasets comprising of DNA methylation, histone acetylation, transcriptome- and genome-wide association studies and quantitative trait loci to further characterize the genetic architecture of AD. We perform co-expression network analysis across more than 1200 human brain samples, identifying robust AD-associated dysregulation of the transcriptome, unaltered in normal human aging. We assess the cell-type specificity of AD gene co-expression changes and estimate cell-type proportion changes in human AD by integrating co-expression modules with single-cell transcriptome data generated from 27 321 nuclei from human postmortem prefrontal cortical tissue. We also show that genetic variants of AD are enriched in a microglial AD-associated module and identify key transcription factors regulating co-expressed modules. Additionally, we validate our results in multiple published human AD gene expression datasets, which can be easily accessed using our online resource (https://swaruplab.bio.uci.edu/consensusAD).
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Gan, Jingyi, Hans-Joachim Sonntag, Mei kuen Tang, Dongqing Cai i Kenneth Ka Ho Lee. "Integrative Analysis of the Developing Postnatal Mouse Heart Transcriptome". PLOS ONE 10, nr 7 (22.07.2015): e0133288. http://dx.doi.org/10.1371/journal.pone.0133288.
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Zhang, Zhe, Zeyad Hailat, Marni J. Falk i Xue-wen Chen. "Integrative analysis of independent transcriptome data for rare diseases". Methods 69, nr 3 (październik 2014): 315–25. http://dx.doi.org/10.1016/j.ymeth.2014.06.003.
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Gusev, Alexander, Arthur Ko, Huwenbo Shi, Gaurav Bhatia, Wonil Chung, Brenda W. J. H. Penninx, Rick Jansen i in. "Integrative approaches for large-scale transcriptome-wide association studies". Nature Genetics 48, nr 3 (8.02.2016): 245–52. http://dx.doi.org/10.1038/ng.3506.
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Li, Shuxin, Jiarui Wang, Jiale Li, Meihong Yue, Chuncheng Liu, Libing Ma i Ying Liu. "Integrative analysis of transcriptome complexity in pig granulosa cells by long-read isoform sequencing". PeerJ 10 (25.05.2022): e13446. http://dx.doi.org/10.7717/peerj.13446.
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Background In intensive and large-scale farms, abnormal estradiol levels in sows can cause reproductive disorders. The high incidence rate of reproductive disturbance will induce the elimination of productive sows in large quantities, and the poor management will bring great losses to the pig farms. The change in estradiol level has an important effect on follicular development and estrus of sows. To solve this practical problem and improve the productive capacity of sows, it is significant to further clarify the regulatory mechanism of estradiol synthesis in porcine granulosa cells (GCs). The most important function of granulosa cells is to synthesize estradiol. Thus, the studies about the complex transcriptome in porcine GCs are significant. As for precursor-messenger RNAs (pre-mRNAs), their post-transcriptional modification, such as alternative polyadenylation (APA) and alternative splicing (AS), together with long non-coding RNAs (lncRNAs), may regulate the functions of granulosa cells. However, the above modification events and their function are unclear within pig granulosa cells. Methods Combined PacBio long-read isoform sequencing (Iso-Seq) was conducted in this work for generating porcine granulosa cells’ transcriptomic data. We discovered new transcripts and possible gene loci via comparison against reference genome. Later, combined Iso-Seq data were adopted to uncover those post-transcriptional modifications such as APA or AS, together with lncRNA within porcine granulosa cells. For confirming that the Iso-Seq data were reliable, we chose four AS genes and analyzed them through RT-PCR. Results The present article illustrated that pig GCs had a complex transcriptome, which gave rise to 8,793 APA, 3,465 AS events, 703 candidate new gene loci, as well as 92 lncRNAs. The results of this study revealed the complex transcriptome in pig GCs. It provided a basis for the interpretation of the molecular mechanism in GCs.
Rozprawy doktorskie na temat "INTEGRATIVE TRANSCRIPTOME"
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Padvitski, Tsimafei. "Integrative analysis of age-related changes in the transcriptome of Caenorhabditis elegans". Thesis, Högskolan i Skövde, Institutionen för biovetenskap, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-11825.
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Ageing is difficult to study because of the complexity and multi-factorial nature of traits that result from a combination of environmental, genetic, epigenetic and stochastic factors, each contributing to the overall phenotype. In light of this challenge, transcriptomic studies of aging organisms are of particular interest, since transcription is an intermediate step that links genotype and phenotype. In recent years microarrays have been widely used for elucidation of changes that occur with age in the transcriptome in Caenorhabditis elegans. However, different microarray studies of C. elegans report sets of differentially expressed genes of varying consistence, with different functional annotations. Failures to find a consistent set of transcriptomic alterations may reflect the absence of a specific genetic program that would guide age-related changes but may also, to some extent, be a consequence of a small sample sizes and a lack of study power in transcriptomic researches. To tackle this issue we analyzed RNA sequences of samples from a time-series experiment of normal aging of C. elegans, performing the first, to our knowledge, NGS-based study of such kind. As a result, evidences were collected that promote a union of two competing theories: the theory of DNA damage accumulation and the theory of programmed aging. Next, we applied two alternative methods, namely the Short Time-series Expression Mining and the Network Smoothing algorithm, in order to obtain and analyze sets of genes that represent distinct modules of age-related changes in the transcriptome. Besides characterization of age-related changes, we were also interested in assessment and validation of the Network Smoothing algorithm. Generally, results of clustering of smoothed scores are consistent with results of short time-series clustering, allowing robust elucidation of functions that are perturbed during aging. At the last phase of the project we questioned if observed changes in the transcriptome can be controlled by specific transcription factors. Thus we used Chip-seq data to predict plausible transcription factor regulators of gene sets obtained using time series clustering and Network smoothing. On the one hand, all predicted transcription factors had documented relevance to aging. On the other hand, we did not achieve gene set specific prediction of transcription factors. In fact, genes with the opposite dynamics were predicted to respond to the same transcription factors. To summarize, we characterized in details age-related changes in the transcriptome of C. elegans, validated the performance of the Network Smoothing algorithm and showed that integration of gene expression with Chip-seq data allows to predict transcription factors that are capable to modulate the lifespan of C. elegans.
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Wilson, Rebecca. "Investigating the Interaction of Monoamines and Diel Rhythmicity on Anti-Predator Behavior in an Orb-Weaving Spider, Larinioides cornutus (Araneae: Araneae)". Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/etd/3441.
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Circadian rhythms are ubiquitous among organisms, influencing a wide array of physiological processes and behaviors including aggression. While many neurophysiological mechanisms are involved in the regulation of aggressive behaviors, relatively few studies have investigated the underlying components involved in the interplay between circadian rhythms and aggression. Spiders are an ideal model system for studying circadian regulation of aggression as they are ecologically both predators and prey. Recent studies have revealed a nocturnal orb- weaving spider Larinioides cornutus exhibits a diel and circadian rhythm in anti-predator behavior (i.e. boldness) that can be manipulated by administration of octopamine (OA) and serotonin (5- HT). Dosing of OA increases boldness of an individual while 5-HT decreases boldness levels. Thus, it appears the serotonergic and octopaminergic system are playing a key role in the daily fluctuations of boldness. This study took a holistic approach to investigate OA and 5-HT levels of head tissue and hemolymph (i.e. blood) as well as the genes involved in synthesis, signaling, and degradation of these monoamines throughout the day (0100, 0700, 1300, and 1900 hours) using HPLC-ED and RNA-sequencing. Although endogenous and circulating levels of OA did not significantly fluctuate, putative transcripts involved in synthesis and signaling did increase in relative expression levels at dusk when L. cornutus begins to actively forage for prey. Endogenous and circulating levels of 5-HT also did not significantly change at the four different time points, but clear patterns of upregulation of 5-HT synthesis enzymes as well as some receptor transcripts were upregulated during the day when L. cornutus would be mostly inactive in its retreat. Lastly, monoamine oxidase, a major catabolic enzyme of monoamines in vertebrates and some invertebrates, was identified in L. cornutus and exhibited substrate specificity for OA compared to 5-HT. Together with the higher enzymatic activity at mid-day compared to dusk, MAO appears to be playing a significant role in regulating the OA and 5-HT signaling in L. cornutus. In conclusion, these results allow a unique preliminary perspective on how OA and 5-HT are influencing the diel shifts in aggression-related behaviors in an ecologically dynamic arthropod.
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Qi, Qin. "An integrative approach to understanding the fitness cost of rifampicin resistance in Pseudomonas aeruginosa". Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:6a82bd64-3b3f-444b-b379-62f01f681594.
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Antibiotic resistance in bacteria is acquired through spontaneous chromosomal mutations or horizontal gene transfer. In the absence of antibiotics, resistant mutants generally show reduced fitness due to compromised growth rate, competitive ability and virulence compared to their antibiotic-sensitive ancestors. The focus of my research is to dissect the molecular underpinnings of the variations in the fitness cost of chromosomal antibiotic resistance using a systems-level approach. From an evolutionary perspective, my research aims are to understand how the fitness cost influences adaptation in resistant populations in an antibiotic-free environment. Using rifampicin resistance in Pseudomonas aeruginosa as a model, my work shows that most of the variation in the fitness cost of rifampicin resistance can be attributed to the direct effect of rifampicin resistance mutations on transcriptional efficiency. Through RNA-Seq transcriptome profiling, I demonstrate that global changes in gene expression levels associated with resistance mutations are surprisingly subtle, suggesting that the transcriptional regulatory network of P. aeruginosa is robust against compromised transcriptional efficiency. Using experimental evolution and whole-genome sequencing, my work reveals a systematic difference in the genetic basis of adaptation in mutants that were propagated in the absence of antibiotics. During compensatory adaptation, resistant mutants can recover the fitness cost of resistance by fixing second-site mutations that directly offset the deleterious effects of resistance mutations. Amongst resistant mutant populations with low fitness costs, general adaptation limits compensatory adaptation, which is most likely to be due to the rarity of compensatory mutations and clonal interference. Far from being the most ubiquitous mechanism in the evolution of resistance, compensatory adaptation is the exception that is more likely to be observed in resistant mutants with high fitness costs. In addition, I applied key elements of the integrative experimental approach developed in this work to dissect the molecular basis of the fitness cost associated with carriage of the pNUK73 small plasmid in P. aeruginosa, which carries the rep gene encoding a plasmid replication protein. My results confirmed that rep expression generates a significant fitness cost in P. aeruginosa and demonstrate how the molecular origins of the fitness cost of resistance can be dissected in a different biological context.
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Dégletagne, Cyril. "Acclimatations des manchots aux contraintes de l’environnement polaire : approches transcriptomique et intégrative sur le manchot Royal (Aptenodytes patagonicus) et le manchot Adélie (Pygoscelis adeliae)". Thesis, Lyon 1, 2011. http://www.theses.fr/2011LYO10348/document.
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King penguins have successfully colonized cold ecosystems of the southern hemisphere by developing physiological mechanisms that are not well understood. The aim of this study was to investigate, at different integrative levels from the gene to the whole animal, the functional responses developed by penguins to overcome polar constrains. We focused on acclimatization mechanisms enabling the first departure to sea of king penguin immatures and the rapid growth of Adélie penguin chicks.To explore differentially expressed genes in pectoralis muscle during penguin’s first sea acclimatization, we used Affymetrix microarrays design for chicken. We first set up and validated a new method to analyze heterologous hybridization transcriptomic profiles. We highlighted a selective shift in metabolic pathways favoring the use of lipids as fuel to sustain highly energetic needs imposed by marine life-style. Our results revealed a development of a global antioxidant response, potential consequences of penguin marine life-style that imposes repeated dives under apnea.Secondly, our integrative study on Adélie penguin’s chick revealed the development of molecular and cellular mechanisms which sustain an original strategy by first allocating most of the energy to growth and then promoting thermogenic processes.Our results showed that both king and Adélie penguins develop complex and coordinated physiological responses to energetic constraints highlighting their high phenotypic plasticityKing penguins have successfully colonized cold ecosystems of the southern hemisphere by developing physiological mechanisms that are not well understood. The aim of this study was to investigate, at different integrative levels from the gene to the whole animal, the functional responses developed by penguins to overcome polar constrains. We focused on acclimatization mechanisms enabling the first departure to sea of king penguin immatures and the rapid growth of Adélie penguin chicks.To explore differentially expressed genes in pectoralis muscle during penguin’s first sea acclimatization, we used Affymetrix microarrays design for chicken. We first set up and validated a new method to analyze heterologous hybridization transcriptomic profiles. We highlighted a selective shift in metabolic pathways favoring the use of lipids as fuel to sustain highly energetic needs imposed by marine life-style. Our results revealed a development of a global antioxidant response, potential consequences of penguin marine life-style that imposes repeated dives under apnea.Secondly, our integrative study on Adélie penguin’s chick revealed the development of molecular and cellular mechanisms which sustain an original strategy by first allocating most of the energy to growth and then promoting thermogenic processes.Our results showed that both king and Adélie penguins develop complex and coordinated physiological responses to energetic constraints highlighting their high phenotypic plasticity
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Nascimento, Leandro Costa do. "Análise de expressão gênica diferencial entre diversas bibliotecas de soja". [s.n.], 2010. http://repositorio.unicamp.br/jspui/handle/REPOSIP/316766.
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Orientador: Gonçalo Amarante Guimarães PereiraDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia
Made available in DSpace on 2018-08-17T20:48:34Z (GMT). No. of bitstreams: 1 Nascimento_LeandroCostado_M.pdf: 1292421 bytes, checksum: e05cfc27d3bf5ae000bfe8b621a750c8 (MD5) Previous issue date: 2010
Resumo: A soja é uma das principais commodities da economia internacional, sendo sua produção mundial de cerca de 220 milhões de toneladas por safra. Além de ser um alimento rico em proteínas e usado para a fabricação de óleo vegetal, a planta vem ganhando visibilidade devido a possibilidade de ser usada na fabricação de biocombustíveis, principalmente o biodiesel. Para o Brasil, a soja tem grande importância na balança comercial, sendo o país o segundo maior produtor do mundo. Neste contexto, no ano de 2007, o governo brasileiro estabeleceu um consórcio de pesquisas em soja - denominado GENOSOJA - com o objetivo de identificar características genéticas que possam facilitar o processo produtivo da planta, com foco nos diversos estresses que acometem a produção nacional, como a ocorrência de secas, o ataque de pragas e a doença da ferrugem asiática, causada pelo fungo Phakopsora pachyrhizi. Este trabalho está inserido no escopo do GENOSOJA, propondo a construção de bancos de dados contendo informações disponíveis nos diversos bancos públicos (sequências genômicas, ESTs e cDNA full-lenght), integrando-as com as informações geradas no decorrer do projeto (tags de SuperSAGE, bibliotecas subtrativas de cDNA e microRNAs). Além disso, foram construídas diversas interfaces web que oferecem aos usuários diversas funcionalidades, incluindo: comparações estatísticas, consultas por palavras-chave, dados sobre anotação e expressão dos genes nas diversas condições e experimentos estudados. Dessa forma, o ferramental de bioinformática aqui apresentado pode facilitar a compreensão de como as diferenças de expressão gênica da planta podem afetar características de importância agronômica
Abstract: Soybean is one of the main commodities in the international economy, with a world production of about 220 millions of tons per harvest. Besides being a protein rich food and used for vegetable oil production, the plant has been gaining visibility due to the possibility of being to make biofuels, especially biodiesel. The soybean culture is of great importance in the Brazilian economy, being the country the second largest producer in the world. In this context, in 2007, the Brazilian government established a research consortium in soybean - called GENOSOJA - aiming to identify genetic traits that may facilitate the production process of the plant, focusing on the different stresses that affect the national production, as the occurrence of drought, pests' attacks and the asian rust disease, caused by the Phakopsora pachyrhizi fungus. This work is inserted in the GENOSOJA, proposing to build a set of databases containing information available in several public databases (genomic sequences, ESTs and full-length cDNA), integrating them with information generated during the project (SuperSAGE tags, cDNA subtractive libraries and miRNAs). Additionally, several web interfaces were built. They offer to users many features, including: statics comparisons, keyword searches, data about annotation and gene expression in different experiments and conditions. Thus, the bioinformatics tools presented here may facilitate the understanding of how the differences in gene expression can affect plant traits with agronomic importance
Mestrado
Bioinformatica
Mestre em Genética e Biologia Molecular
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Chintapalli, Venkateswara Rao. "An integrative and systems biology approach to Drosophila melanogaster transcriptomes". Thesis, University of Glasgow, 2012. http://theses.gla.ac.uk/3361/.
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The availability of fully sequenced genomes of the model organisms including Drosophila, and their subsequent annotation has afforded seamless opportunities for reverse genetics in a complex model organism. With the advent of DNA microarrays to assay the levels of tens of thousands of genes in a single sample, functional genomics has been significantly aided to understand the functions in systems context. These microarrays have been employed predominantly on the RNA samples that are extracted from the whole animals for example at different developmental stages or in response to external stimuli. However, these approaches relied on the expression patterns that represent the sum of transcription coming from all the organs, which do not estimate the tissue-specificity of transcription. The purpose of this thesis is to provide tissue-specific transcriptomes of Drosophila melanogaster that were generated as part of the large FlyAtlas project using Affymetrix Drosophila GeneChips® (or microarrays). These chips, one at a time interrogate the levels of 18,500 transcripts (that represent all known genes) using 18,880 distinct probe sets in a single, total RNA sample. For each tissue, four biological replicates were analysed using the chips and the normalised signal intensities were obtained that represent the relative levels of mRNA expression. Using the transcriptomes, a general analysis was performed for potential novel insights into tissue-specific functions (Chintapalli et al., 2007) (Chapter 3). Then, a comparative analysis of epithelial tissues was performed to understand how the epithelia are organised in terms of their transcriptomes (Chapter 4). The Malpighian tubules are the Drosophila epithelial counterparts of the human kidney. They show asymmetric organisation in the body cavity. FlyAtlas segment-specific tubule transcriptomes allowed the comparison of their potential functional similarities and differences, thus to understand the asymmetry in function (Chapter 5)(Chintapalli, 2012). This identified a human Best vitelliform macular dystrophy (BVMD) disease homolog, Best2 in only the anterior pair of tubules that have the morphologically and functionally distinct enlarged initial (or distal) segment, a storage organ for Ca2+. Bestrophins were accordingly selected as candidate genes to analyse organismal functions, and thus to validate previous two theories that implicated bestrophins as Ca2+-activated Clˉ channels and/or Ca2+ channel regulators (Chapter 6). The confocal microscopy analysis of bestrophin YFP fusion proteins revealed interesting and novel localisations of bestrophins, in that Best1 was found in the apical plasma membranes, Best2 localised to peroxisomes, Best3 and Best4 were found intracellular. The salt survival analysis showed that Best1 is essential in regulating extra salt levels in the body. Furthermore, the fluid secretion analysis showed Best1’s potential role in Ca2+-dependent Clˉ function. Interestingly, the flies with reduced levels of Best2 expression showed increased ability to survive on extra salt food; the basis for this was investigated further in Chapter 7. Best2 was also found abundant in the eyes than anywhere else in the head. A comparative analysis of anterior tubule- and eye-specific transcriptomes revealed a potential overlap of Ca2+ signaling components, in that the PLCβ signaling was one. A neuropeptide Ca2+ agonist, capa1 evoked secondary cytosolic Ca2+ responses were found high in Best2 knockdowns. A quantitative PCR (qPCR) analysis of candidate Ca2+ signaling and homeostasis genes in Best2 mutants revealed their gene expression upregulation, under control-fed and salt-fed conditions than their wildtype controls, fed on similar diet regimes. The norpA that encodes PLCβ was found significantly enriched in the mutants. Cyp6a23 is another gene that was highly upregulated in Best2 mutants; it is a Drosophila homologue of human Cyp11b, a Ca2+-responsive gene implicated in renal salt wasting. Upon the downregulation of Cyp6a23, flies became sensitive to salt diet feeding. Other genes investigated and found to be upregulated in the mutants include transient-receptor-potential (trp) Ca2+ channel and retinal degeneration C (rdgC). Together, these results strongly suggest Best2 as a potential Ca2+ channel regulator, and provide fascinating insight into bestrophin function. Peroxisomal localisation of Best2 in line with the implication that peroxisomes act as dynamic regulators of cell Ca2+ homeostasis led to another aspect of the project (Chapter 8). This study identified two peroxins that are most abundant in the tubules and play essential roles in the novel cyclic nucleotide-regulated peroxisomal Ca2+ sequestration and transport pathway and that are detrimental for peroxisome biogenesis and proliferation.
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Mutwil, Marek. "Integrative transcriptomic approaches to analyzing plant co-expression networks". Phd thesis, Universität Potsdam, 2011. http://opus.kobv.de/ubp/volltexte/2011/5075/.
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It is well documented that transcriptionally coordinated genes tend to be functionally related, and that such relationships may be conserved across different species, and even kingdoms. (Ihmels et al., 2004). Such relationships was initially utilized to reveal functional gene modules in yeast and mammals (Ihmels et al., 2004), and to explore orthologous gene functions between different species and kingdoms (Stuart et al., 2003; Bergmann et al., 2004).
Model organisms, such as Arabidopsis, are readily used in basic research due to resource availability and relative speed of data acquisition. A major goal is to transfer the acquired knowledge from these model organisms to species that are of greater importance to our society. However, due to large gene families in plants, the identification of functional equivalents of well characterized Arabidopsis genes in other plants is a non-trivial task, which often returns erroneous or inconclusive results.
In this thesis, concepts of utilizing co-expression networks to help infer (i) gene function, (ii) organization of biological processes and (iii) knowledge transfer between species are introduced. An often overlooked fact by bioinformaticians is that a bioinformatic method is as useful as its accessibility. Therefore, majority of the work presented in this thesis was directed on developing freely available, user-friendly web-tools accessible for any biologist.Es ist bereits ausgiebig gezeigt worden, dass Gene, deren Expression auf Transkriptionsebene koordiniert ist, häufig auch funktional in verwandten Stoffwechselwegen vorkommen, und dass sich dies wahrscheinlich auch Spezies- und sogar Reichübergreifend sagen lässt (Ihmels et al., 2004). Anfänglich wurden solche Beziehungen verwendet, um sogenannte Genfunktionsmodule in Hefe und Säugern aufzudecken (Ihmels et al., 2004), um dann orthologe Genfunktionen zwischen verschiedene Spezies und Reichen zu entdecken (Stuart et al., 2003; Bergmann et al., 2004). Modellorganismen wie Arabidopsis werden bevorzugt in der Forschung verwendet, weil man durch die schnelle Generationszeit in kurzer Zeit viele Daten erheben kann und aufgrund dessen die Ressourcen- und Informationsvielfalt um ein Vielfaches größer ist. Ein Hauptziel ist der Wissenstransfer von Modellorganismen auf Spezies, die gesellschaftlich von höherer Bedeutung sind wie z.B. Getreidearten oder andere Feldfrüchte. Pflanzen besitzen oft große Genfamilien und die eindeutige Identifizierung von gut charakterisierten Arabidopsisorthologen in besagten Nutzpflanzen ist kein triviales Vorhaben. In der vorliegenden Arbeit werden Konzepte zur Nutzung von Co-expressionsnetzwerken beschrieben, die helfen sollen (i) Genfunktionen zu identifizieren, (ii) die Organisation von biologischen Prozessen aufzuklären und (iii) das erworbene Wissen auf andere Spezies übertragbar zu machen. Ein häufig von Bioinformatikern übersehender Umstand ist, dass bioinformatische Methoden nur so sinnvoll sind wie ihre Zugänglichkeit. Deshalb basiert der Großteil dieser Arbeit auf freiverfügbaren und vor allem für Biologen nutzerfreundlichen Webtools.
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Tarabichi, Maxime. "Integrative analyses of genome-wide transcriptomic and genomic thyroid cancer profiles". Doctoral thesis, Universite Libre de Bruxelles, 2016. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/225138.
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Cette thèse en bioinformatique a été réalisée entre 2010 et 2015 dans le groupe du Pr. Vincent Detours à l’Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire. Nous avons analysé des données génomiques et transcriptomiques provenant de carcinomes papillaires de la thyroïde (CPTs) et leurs tissus non-cancéreux adjacents. La première partie étudiait les différences transcriptomiques entre CPTs post-Tchernobyl et CPTs sporadiques, et leur tissus non-cancéreux adjacents. Dans notre cohorte, les cas sporadiques étaient en moyenne et significativement un an plus jeunes. Après un ajustement des données transcriptionnelles pour l'âge, près de 400 gènes étaient plus exprimés dans les tissus adjacents des patients exposés aux radiations. Cependant, nous n’avons pu détecter aucune surreprésentation de groupe de gènes participant à des fonctions biologiques connues. Il était possible de distinguer les cas sporadiques des cas post-Tchernobyl sur base des transcriptomes de leurs tissus adjacents, avec une précision de ~70%. Cette surexpression de gènes dans les tissus non-cancéreux adjacents pourrait être liée à une radiosensibilité accrue dans le groupe des patients exposés aux radiations de Tchernobyl. Dans la deuxième étude, nous avons intégré des données provenant des patients de la première partie, incluant les nombres de copies d'ADN des CPTs, le génotype de plus de 400.000 SNPs dans le sang et les données transcriptionnelles des CPTs et leurs tissus non-cancéreux adjacents. En reproduisant les résultats d'une étude précédente, nous avons retrouvé la région 7q11.23 dupliquée exclusivement dans un tiers des patients exposés aux radiations. Dans une étude indépendante, un autre groupe a montré que la duplication de cette région était plus fréquente dans une population de lignées cellulaires radiosensibles que dans la population humaine normale. Cependant, en analysant les transcriptomes des patients présentant cette duplication, nous n'avons pas détecté de différence d’expression des gènes codés dans cette région génomique. En outre, aucun génotype de SNP n'était significativement lié à l'exposition aux radiations. En conclusion, les résultats confirment qu'un tiers des CPTs post-Tchernobyl ont des traces d'un dégât radio-sensibilsant dans leur ADN. Dans une troisième étude, nous avons étudié les différences transcriptionnelles entre CPTs et leurs métastases ganglionnaires (MGs) associées, ainsi qu'entre des CPTs développant des MGs (N+) et des CPTs ne développant pas de MGs (N0). Des études précédentes comparant les MGs et leurs tumeurs associées impliquant d’autres organes ont montré une surexpression de gènes dans les MGs, liés aux cellules immunitaires. Ce signal provient du tissu contaminant environnant les MGs. Pour se défaire de ce signal contaminant, d’autres études ont microdisséqué au laser les parties tumorales des MGs. Cependant, la microdissection retire aussi le stroma associé à la tumeur, alors que celui-ci est justement impliqué dans la progression tumorale. Grâce à une méthode originale, nous avons corrigé nos données d’expression des MGs pour leur contenu en contaminant ganglionnaire non-cancéreux. Après cette correction, l’expression de gènes liés au stroma était plus élevée dans les MGs que dans leurs CPTs. Les différences d’expression entre N0 et N+ n’étaient pas reproductibles entre 4 jeux de données indépendants de CPTs. Ceci démontre l’absence d’un signal transcriptionnelle lié au statut nodal dans ces données. Cependant, en utilisant des données publiques comprenant des centaines de tumeurs, il est possible de prédire le statut nodal (N0 ou N+) des CPTs ainsi que des cancers du sein et du colon à partir de leurs transcriptomes. Des études précédentes montraient des taux de prédiction presque parfaits (>90%) du statut nodal à partir des données transcriptomiques. Nous avons décelés dans ces études le même biais technique de sélection des gènes, qui peut expliquer ces taux artificiellement élevés. Dans notre étude, ce biais n’était pas présent et la précision de nos prédictions était limitée (<70%), questionnant l’intérêt clinique de telles prédictions. La présence d’un signal permettant de prédire le statut nodal et l’irreproductibilité de ce signal dans des jeux de données indépendants peuvent s'expliquer par l’association entre le statut nodal et des caractéristiques d'agressivité des tumeurs, qui pourraient, elles, avoir une influence reproductible sur les transcriptomes. Dans notre dernière étude, nous avons analysé les différences entre CPTs, liées à la présence de BRAFV600E, une mutation commune à 60% des CPTs. En utilisant un jeu de données public, nous avons montré que les CPTs présentant la mutation étaient plus dédifférenciés, et plus infiltrés en stroma, probablement en lymphocytes et fibroblastes; et que ces CPTs présentaient plus de fibrose et proliféraient sans doute plus. Tout ceci suggère que les CPTs mutés pour BRAF constituent un groupe de CPTs plus agressif. Des caractéristiques d’agressivité pourraient être détectées au front invasif, c’est-à-dire la périphérie de la tumeur définissant son contact avec le stroma, notamment la présence de regroupement de cellules isolées du reste de la tumeur. Dans les CPTs, ces îlots cellulaires isolés sont observés sur des lames histologiques 2D et pourraient être expliqués soit par un détachement cellulaire, signe d’agressivité lié au processus métastatique, soit une conformation complexe compatible avec une tumeur connexe en 3D. Dans un CPT, nous avons analysé la conformation 3D du front invasif d'un CPT muté. Nous avons reconstruit son volume 3D grâce à une méthode originale. Les groupes de cellules cancéreuses qui semblaient isolées sur les images 2D d’histopathologie, étaient en fait connectés en 3D. L’hypothèse de la présence de détachement cellulaire suite à la transition épithélio-mésenchymateuse n’est donc pas requise pour expliquer la présence de ces îlots cellulaires en 2D. La forme 3D du front invasif impliquait une surface de contact entre tumeur et stroma bien plus importante qu'impliquée par la forme ellipsoïde habituellement décrite. Les fibroblastes participaient autant à la création de la masse tumorale que les cellules cancéreuses, puisque ces deux groupes de cellules proliféraient à la même vitesse. A l'avenir, le séquençage du matériel génétique de cellules individuelles facilitera notre interprétation des signaux génomiques et transcriptomiques, qui jusqu’alors provenaient de tissu complet, i.e. un mélange de populations de cellules tumorales, stromales et de contaminant. Une signature de radiation pourrait être extraite des profils mutationnels de cellules individuelles exposées aux radiations et à l’H2O2 in vitro et comparée à la signature des CTPs post-Tchernobyl. Les cellules tumorales et stromales individuelles des MGs pourraient être comparées aux cellules tumorales et stromales invividuelles des CPTs. De même les cellules individuelles mutées pour BRAFV600E pourraient être comparées aux cellules non mutées.Doctorat en Sciences biomédicales et pharmaceutiques (Médecine)
info:eu-repo/semantics/nonPublished
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Lin, Tiffany J. "Multinet Bayesian network models for large-scale transcriptome integration in computational medicine". Thesis, Massachusetts Institute of Technology, 2012. http://hdl.handle.net/1721.1/77535.
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Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2012.Cataloged from PDF version of thesis.
Includes bibliographical references (p. 30).
Motivation: This work utilizes the closed loop Bayesian network framework for predictive medicine via integrative analysis of publicly available gene expression findings pertaining to various diseases and analyzes the results to determine which model, single net or multinet, is a more accurate predictor for determining disease status. Results: In general, it is suggested to use the multinet Bayesian network framework for predictive medicine instead of the single net Bayesian network, because for large numbers of samples and features, it is highly likely that it is the stronger predictor, and for smaller numbers of samples and features, if the multinet returns good results, it is likely to be a better predictor than the single net Bayesian network.
by Tiffany J. Lin.
M.Eng.
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Cui, Chenming. "Integrating bioinformatic approaches to promote crop resilience". Diss., Virginia Tech, 2019. http://hdl.handle.net/10919/94424.
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Even under the best management strategies contemporary crops face yield losses from diverse threats such as, pathogens, pests, and environmental stress. Adding to this management challenge is that under current global climate projections these impacts are predicted to become even greater. Natural genetic variation, long used by traditional plant breeders, holds great promise for adapting high performing agronomic lines to these stressors. Yet, efforts to bolster crop plant resilience using wild relatives have been hindered by time consuming efforts to develop genomic tools and/or identify the genetic basis for agronomic traits. Thus, increasing crop plant resilience requires developing and deploying approaches that leverage current high-throughput sequencing technologies to more rapidly and robustly develop genomic tools in these systems. Here we report the integration of bioinformatic and statistical tools to leverage high-throughput sequencing to 1) develop a machine learning approach to determine factors impacting transcriptome assembly and quantitatively evaluate transcriptome completeness, 2) dissect complex physiological pathway interactions in Solanum pimpinellifolium under combined stresses—using comparative transcriptomics, and 3) develop a genome assembly pipeline that can be deployed to rapidly assemble a more contiguous genome, unraveling previously hidden complexity, using Phytopthora capsici as a model. As a result, we have generated strategic guidelines for transcriptome assembly and developed an orthologue and reference free, machine learning based tool "WWMT" to quantitatively score transcriptome completeness from short read data. Secondly, we identified "hub genes" and describe genes involved with "cross-talk" between drought and herbivore stress response pathways. Finally, we demonstrate a protocol for combining long-read sequencing from the Oxford Nanopore Technologies MinION, and short-read data, to rapidly assembly a cost-effective, contiguous and relatively complete genome. Here we uncovered hidden variation in a well-known plant pathogen finding that the genome was 92% bigger than previous estimates with more than 39% of duplicated regions, supporting a hypothesized recent whole genome duplication in this clade. This community resource will support new functional and evolutionary studies in this economically important pathogen.Doctor of Philosophy
Meeting the food production demands of a burgeoning population in a changing environment, means adapting crop plants to become more resilient to environmental stress. One of the greatest barriers to understanding and predicting crop responses to future environmental change is our poor understanding of the functional and genomic basis of stress resistance traits for contemporary crops. This impediment presents a barrier for rapid crop improvement technologies, such as, gene editing or genomic selection, that is only partially overcome by generating large amounts of sequencing data. Here we need tools that allow us to process and evaluate huge amounts of data generated from next generation sequencing studies to help identify genomic regions associated with agronomic traits. We also need technical approaches that allow us to disentangle the complex genetic interactions that drive plant stress responses. Here we present work that used statistical analysis and recent advances of artificial intelligence to develop a bioinformatic approach to evaluate genomic sequencing data prior to downstream analyses. Secondly, we used a reductionist approach to filter thousands of genes to key genes associated with combined stress responses (herbivory and drought), in the most widely used vegetable in the world, tomato. Finally, we developed a method for generating whole genome sequences that is low-cost and time sensitive and tested it using a well-known plant pathogen genome, wherein we unraveled significant hidden complexity. Overall this work provides community-wide genomic tools and information to promote crop resilience.
Książki na temat "INTEGRATIVE TRANSCRIPTOME"
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Grant, Warren, i Martin Scott-Brown. Principles of oncogenesis. Redaktorzy Patrick Davey i David Sprigings. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199568741.003.0322.
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It is obvious that the process of developing cancer—oncogenesis—is a multistep process. We know that smoking, obesity, and a family history are strong independent predictors of developing malignancy; yet, in clinics, we often see that some heavy smokers live into their nineties and that some people with close relatives affected by cancer spend many years worrying about a disease that, in the end, they never contract. For many centuries scientists have struggled to understand the process that make cancer cells different from normal cells. There were those in ancient times who believed that tumours were attributable to acts of the gods. Hippocrates suggested that cancer resulted from an imbalance between the black humour that came from the spleen, and the other three humours: blood, phlegm, and bile. It is only in the last 100 years that biologists have been able to characterize some of the pathways that lead to the uncontrolled replication seen in cancer, and subsequently examine exactly how these pathways evolve. The rampant nature by which cancer invades local and distant tissues, as well its apparent ability to spread between related individuals led some, such as Peyton Rous in 1910, to suggest that cancer was an infectious condition. He was awarded a Nobel Prize in 1966 for the 50 years of work into investigating a link between sarcoma in chickens and a retrovirus that became known as Rous sarcoma virus. He had shown how retroviruses are able to integrate sequences of DNA coding for errors in cellular replication control (oncogenes) by introducing into the human cell viral RNA together with a reverse transcriptase. Viruses are now implicated in many cancers, and in countries where viruses such as HIV and EBV are endemic, the high incidence of malignancies such as Kaposi’s sarcoma and Burkitt’s lymphoma is likely to be directly related. There are several families of viruses associated with cancer, broadly classed into DNA viruses, which mutate human genes using their own DNA, and retroviruses, like Rous sarcoma virus, which insert viral RNA into the cell, where it is then transcribed into genes. This link with viruses has not only led to an understanding that cancer originates from genetic mutations, but has also become a key focus in the design of new anticancer therapies. Traditional chemotherapies either alter DNA structure (as with cisplatin) or inhibit production of its component parts (as with 5-fluorouracil.) These broad-spectrum agents have many and varied side effects, largely due to their non-specific activity on replicating DNA throughout the body, not just in tumour cells. New vaccine therapies utilizing gene-coding viruses aim to restore deficient biological pathways or inhibit mutated ones specific to tumour cells. The hope is that these gene therapies will be effective and easily tolerated by patients, but development is currently progressing with caution. In a trial in France of ten children suffering from X-linked severe combined immunodeficiency and who were injected with a vector that coded for the gene product they lacked, two of the children subsequently died from leukaemia. Further analysis confirmed that the DNA from the viral vector had become integrated into an existing, but normally inactive, proto-oncogene, LM02, triggering its conversion into an active oncogene, and the development of life-threatening malignancy. To understand how a tiny change in genetic structure could lead to such tragic consequences, we need to understand the molecular biology of the cell and, in particular, to pay attention to the pathways of growth regulation that are necessary in all mammalian cell populations. Errors in six key regulatory pathways are known as the ‘hallmarks of cancer’ and will be discussed in the rest of this chapter.
Części książek na temat "INTEGRATIVE TRANSCRIPTOME"
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Berger, Emily, Deniz Yorukoglu i Bonnie Berger. "HapTree-X: An Integrative Bayesian Framework for Haplotype Reconstruction from Transcriptome and Genome Sequencing Data". W Lecture Notes in Computer Science, 28–29. Cham: Springer International Publishing, 2015. http://dx.doi.org/10.1007/978-3-319-16706-0_4.
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Benabdellah, Karim, Simone Thomas i Hinrich Abken. "Genetic Engineering of Autologous or Allogeneic Immune Effector Cells". W The EBMT/EHA CAR-T Cell Handbook, 7–10. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-030-94353-0_2.
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AbstractManufacturing immune effector cells (T or NK cells) with CAR-encoding DNA sequences requires efficient and safe genetic engineering procedures. For this purpose, an appropriate genetic vector is chosen according to numerous factors, including the vector genome packaging capacity, cellular tropism, genomic integration, immune toxicity, and other factors. In clinical trials, genomes integrating viral vectors, in particular vectors based on members of the Retroviridae family, such as retroviruses and lentiviruses, have been successfully used for more than 20 years. These vectors contain an RNA genome that when transcribed into double-stranded DNA by reverse transcriptase integrates into the genome of the transduced cell.
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da Silva Filho, Reginaldo Inojosa, Ricardo Luis de Azevedo da Rocha i Claudio Santos Oliveira. "Formal Language Model for Transcriptome and Proteome Data Integration". W Computational Science and Its Applications – ICCSA 2020, 727–35. Cham: Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-58814-4_60.
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Uzun, Yasin, Hao Wu i Kai Tan. "Integrating Single-Cell Methylome and Transcriptome Data with MAPLE". W Methods in Molecular Biology, 43–54. New York, NY: Springer US, 2023. http://dx.doi.org/10.1007/978-1-0716-2962-8_4.
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Cassese, Alberto, Michele Guindani i Marina Vannucci. "iBATCGH: Integrative Bayesian Analysis of Transcriptomic and CGH Data". W Statistical Analysis for High-Dimensional Data, 105–23. Cham: Springer International Publishing, 2016. http://dx.doi.org/10.1007/978-3-319-27099-9_6.
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Sagan, April, Xiaojun Ma, Koushul Ramjattun i Hatice Ulku Osmanbeyoglu. "Linking Expression of Cell-Surface Receptors with Transcription Factors by Computational Analysis of Paired Single-Cell Proteomes and Transcriptomes". W Cancer Systems and Integrative Biology, 149–69. New York, NY: Springer US, 2023. http://dx.doi.org/10.1007/978-1-0716-3163-8_11.
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Sirdeshmukh, Ravi, Savita Jayaram, Manoj Kumar Gupta, Pranali Sonpatki, Manika Singh, Raksha A. Ganesh, Chaitra B. Amaresha i Nameeta Shah. "Integration of Transcriptomic and Proteomic Data for Disease Insights". W Neuromethods, 325–56. New York, NY: Springer New York, 2017. http://dx.doi.org/10.1007/978-1-4939-7119-0_20.
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Forestan, Cristian, Silvia Farinati, Alice Lunardon i Serena Varotto. "Integrating Transcriptome and Chromatin Landscapes for Deciphering the Epigenetic Regulation of Drought Response in Maize". W Compendium of Plant Genomes, 97–112. Cham: Springer International Publishing, 2018. http://dx.doi.org/10.1007/978-3-319-97427-9_7.
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Garcia, Maxime, Pascal Finetti, Francois Bertucci, Daniel Birnbaum i Ghislain Bidaut. "Detection of Driver Protein Complexes in Breast Cancer Metastasis by Large-Scale Transcriptome–Interactome Integration". W Gene Function Analysis, 67–85. Totowa, NJ: Humana Press, 2013. http://dx.doi.org/10.1007/978-1-62703-721-1_5.
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Gonzalez, Luis Miguel, Elena Sevilla, Miguel Fernández-García, Alejandro Sanchez-Flores i Estrella Montero. "Integration of Genomic and Transcriptomic Data to Elucidate Molecular Processes in Babesia divergens". W Methods in Molecular Biology, 199–215. New York, NY: Springer US, 2021. http://dx.doi.org/10.1007/978-1-0716-1681-9_12.
Pełny tekst źródłaStreszczenia konferencji na temat "INTEGRATIVE TRANSCRIPTOME"
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Park, Sungmin, Junghyun Jung i Jong Wha Joanne Joo. "Integrative Meta-analysis of Transcriptome Data for Unmasking Biological Mechanism of Idiopathic pulmonary fibrosis". W 2020 Joint 11th International Conference on Soft Computing and Intelligent Systems and 21st International Symposium on Advanced Intelligent Systems (SCIS-ISIS). IEEE, 2020. http://dx.doi.org/10.1109/scisisis50064.2020.9322727.
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BenHamadou1, Alexandra Leitao, Zenaba Khatir, Noora Al-Shamary, Hassan Hassan, Zainab Hizan, Aisha Al-Ashwal, Mark Chatting i in. "Pearl Oyster: From National Icon To Guardian of Qatar's Marine Environment". W Qatar University Annual Research Forum & Exhibition. Qatar University Press, 2020. http://dx.doi.org/10.29117/quarfe.2020.0051.
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The NPRP9-394-1-090 project “Pearl Oyster: from national icon to guardian of Qatar's marine environment” had as main aim to develop and apply an integrated suite of chemical and biological methods as early warning tools to assess the “health” of Qatar’s marine environment. The central theme consisted in an investigative monitoring program around the use of the pearl oyster, Pictada imbricata radiata, as a sentinel or guardian species. We have characterized the main environmental contaminants of concern at a selected number of sites around the Qatari coast (UmmBab, Al Khor, Al Wakra and Simaisma), during 2 years, in summer and winter. Potential ecological effects of contaminants (targeted and untargeted) were investigated at different biological organization levels (gene, chromosome, cell, individual, population), through a multidisciplinary approach, using classical and genotoxicological endpoints, integrative histopathology and transcriptomic responses to the different environmental stresses. To our knowledge, this is the first time an integrated approach connecting all these disciplines has been applied in the Qatari marine environment. We present here the main results, of this 3 years project, obtained in all different disciplinary approaches. The results of this project will leave a legacy of resources for future Qatari researchers, including an open access transcriptome data base and the first description of common pathologies observed in the pearl oyster P. i. radiata. Moreover, they will also represent a sound science-based baseline data essential for conservation and management planning, by integration of the data from all the different disciplines applied in the project to assess the potential ecological effects of contaminants at different biological levels.
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Rohr, Michael W., i Deborah Altomare. "Abstract 2309: Predicting molecular networks mediating colorectal cancer neoplastic progression by integrative transcriptome-wide meta-analysis". W Proceedings: AACR Annual Meeting 2021; April 10-15, 2021 and May 17-21, 2021; Philadelphia, PA. American Association for Cancer Research, 2021. http://dx.doi.org/10.1158/1538-7445.am2021-2309.
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Shern, Jack F., Li Chen, Juliann Chmielecki, Jun Wei, Rajesh Patidar, Young Song, Hongling Liao i in. "Abstract A21: Integrative genome and transcriptome sequencing defines the landscape of genetic alterations underlying pediatric rhabdomyosarcoma". W Abstracts: AACR Special Conference: Pediatric Cancer at the Crossroads: Translating Discovery into Improved Outcomes; November 3-6, 2013; San Diego, CA. American Association for Cancer Research, 2014. http://dx.doi.org/10.1158/1538-7445.pedcan-a21.
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Zhang, Jinghui, Michael Rusch, Joy Nakitandwe, Zhaojie Zhang, Michael N. Edmonson, Matthew Parker, Xiaotu Ma i in. "Abstract 2628: Molecular diagnosis for pediatric cancer through integrative analysis of whole-genome, whole-exome and transcriptome sequencing". W Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1538-7445.am2016-2628.
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Xia, Jun, Zhuoyi Song i Chris Amos. "Abstract 3532: Post-GWAS in lung cancer: From transcriptome-wide association to the DNA damageome by Integrative functional screens". W Proceedings: AACR Annual Meeting 2020; April 27-28, 2020 and June 22-24, 2020; Philadelphia, PA. American Association for Cancer Research, 2020. http://dx.doi.org/10.1158/1538-7445.am2020-3532.
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Kim, Yon Hui, Han Liang, Xiuping Liu, Julie Izzo, Robert Lemos, Ju-Seog Lee, Jae Yong Cho i in. "Abstract 970: Multi-layer and integrative analysis of the whole transcriptome in Asian gastric cancer: AMPKβ modulation in cancer progression". W Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL. American Association for Cancer Research, 2012. http://dx.doi.org/10.1158/1538-7445.am2012-970.
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Pomponio, Robert, Qi Tang, Anthony Mei, Anne Caron, Bema Coulibaly, Joachim Theihaber, Maximilian Rogers-Grazado, Tun Tun Lin i Rui Wang. "Abstract 345: An integrative approach of image analysis and transcriptome profiling to explore potential predictive biomarkers for TGF-beta blockade therapy". W Proceedings: AACR Annual Meeting 2021; April 10-15, 2021 and May 17-21, 2021; Philadelphia, PA. American Association for Cancer Research, 2021. http://dx.doi.org/10.1158/1538-7445.am2021-345.
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Di Liberto, Maurizio, Peter Martin, David Chiron, Priyanka Vijay, Xiangao Huang, Pedro Blecua, Scott Ely i in. "Abstract 3095: Longitudinal integrative whole transcriptome and exome sequencing identifies genes that reprogram lymphoma cells for clinical response to CDK4/6 inhibition in combination therapy". W Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1538-7445.am2015-3095.
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Chudasama, Priya, Sadaf Mughal, Mathijs Sanders, Daniel Hübschmann, Inn Chung, Aurélie Ernst, Bernd Kasper i in. "Abstract 4336: Integrative genomic and transcriptomic analysis of leiomyosarcoma". W Proceedings: AACR Annual Meeting 2018; April 14-18, 2018; Chicago, IL. American Association for Cancer Research, 2018. http://dx.doi.org/10.1158/1538-7445.am2018-4336.
Pełny tekst źródłaRaporty organizacyjne na temat "INTEGRATIVE TRANSCRIPTOME"
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Tucker, Mark L., Shimon Meir, Amnon Lers, Sonia Philosoph-Hadas i Cai-Zhong Jiang. Elucidation of signaling pathways that regulate ethylene-induced leaf and flower abscission of agriculturally important plants. United States Department of Agriculture, styczeń 2012. http://dx.doi.org/10.32747/2012.7597929.bard.
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The Problem: Abscission is a highly regulated process, occurring as a natural terminal stage of development, in which various organs are separated from the parent plant. In most plant species, the process is initiated by a decrease in active auxin in the abscission zone (AZ) and an increase in ethylene, and may be accelerated by postharvest or environmental stresses. Another potential key regulator in abscission is IDA (Inflorescence Deficient in Abscission), which was identified as an essential peptide signal for floral organ abscission in Arabidopsis. However, information is still lacking regarding the molecular mechanisms integrating all these regulators. In our previous BARD funded research we made substantial progress towards understanding these molecular events in tomato, and the study is still in progress. We established a powerful platform for analysis of genes for regulatory proteins expressed in AZ. We identified changes in gene expression for several transcription factors (TFs) directly linked to ethylene and auxin signaling and several additional regulatory proteins not so obviously linked to these hormones. Moreover, we demonstrated using a virus-induced gene silencing (VIGS) assay that several play a functional role in the onset of abscission. Based on these results we have selected 14 genes for further analysis in stably transformed tomato plants. All 14 genes were suppressed by RNA interference (RNAi) using a constitutive promoter, and 5 of them were also suppressed using an abscission-specific promoter. Transformations are currently at different stages of progress including some lines that already display an abscission phenotype. Objectives: We propose here to (1) complete the functional analysis of the stably transformed tomato plants with T2 lines and perform transcriptome analysis using custom abscission-specific microarrays; (2) conduct an indepth analysis of the role of IDA signaling in tomato leaf and flower abscission; (3) perform transcriptome and proteome analyses to extend the earlier gene expression studies to identify transcripts and proteins that are highly specific to the separation layer (i.e., target cells for cell separation) prior to the onset of abscission; (4) extend and compliment the work in tomato using a winnowed set of genes in soybean. Methodology: Next Generation Sequencing (NGS) of mRNA will be used to further increase the list of abscission-associated genes, and for preparation of a custom tomato abscission microarray to test altered gene expression in transgenic plants. Tandem mass spectrometry (LC-MS/MS) of protein extracts from leaf petiole, flower pedicel and their AZ tissues will be used to identify the proteome of the AZ before and during abscission. AZ-specific gene promoters will be used in stably transformed tomato plants to reduce non-target phenotypes. The bean pod mottle virus (BPMV) plasmid vectors will be used for VIGS analysis in soybean. Expected Contribution: Our study will provide new insights into the regulation of ethylene-induced abscission by further revealing the role of key regulators in the process. This will permit development of novel techniques for manipulating leaf and flower abscission, thereby improving the postharvest performance of agriculturally important crops.
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Dudareva, Natalia, Alexander Vainstein, Eran Pichersky i David Weiss. Integrating biochemical and genomic approaches to elucidate C6-C2 volatile production: improvement of floral scent and fruit aroma. United States Department of Agriculture, wrzesień 2007. http://dx.doi.org/10.32747/2007.7696514.bard.
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The specific objectives of approved proposal include to: 1. Elucidate the C6-C2 biochemical pathways leading to the biosynthesis of phenylacetaldehyde, phenylethyl alcohol and phenylethyl acetate in floral tissues of ornamentally important plants, pefunia and roses. 2. Isolate and characterrze genes responsible for the production of these C6-C2 compounds and those involved in the regulation of the pathway using genomic and transcriptomic tools. 3. Determine whether altering the expression of key genes of this pathway can result in changing the aroma characteristics of flowers. Aldehydes are intermediates in a variety of biochemical pathways including those involved in the metabolism of carbohydrates, vitamins, steroids, amino acids, benzylisoquinoline alkaloids, hormones, and lipids. In plants they are also synthesized in response to environmental stresses such as salinity, cold, and heat shock or as flavors and aromas in fruits and flowers. Phenylacetaldehyde along with 2-phenylethanol and its acetate ester, are important scent compounds in numerous flowers, including petunias and roses. However, little is known about the biosynthesis of these volatile compounds in plants. We have shown that the formation PHA and 2-phenylethanol from Phe does not occur via trans-cinnamic acid and instead competes with the key enzyme of phenypropanoid metabolism Pheammonia-lyase (PAL) for Phe utilization. Using functional genomic approach and comparative gene expression profiling, we have isolated and characterized a novel enzyme from petunia and rose flowers that catalyzes the formation of the Ca-Czcompound phenylacetaldehyde (PHA) from L-phenylalanine (Phe) by the removal of both the carboxyl and amino groups. This enzyme, designated as phenylacetaldehyde synthases (PAAS), is a bifunctional enzyme that catalyzes the unprecedented efficient coupling of phenylalanine decarboxylation to oxidation, generating phenylacetaldehyde, CO2, ammonia, and hydrogen peroxide in stoichiometric amounts. Down-regulation of PAAS expression via RNA interference-based (RNAi) technology in petunia resulted in no PHA emission when compared with controls. These plants also produced no 2-phenylethanol, supporting our conclusion that PHA is a precursor of 2-phenylethanol. To understand the regulation of scent formation in plants we have also generated transgenic petunia and tobacco plants expressing the rose alcohol acetyltransferase (RhAAT) gene under the control of a CaMV-35S promoter. Although the preferred substrate of RhAAT in vitro is geraniol, in transgenic petunia flowers, it used phenylethyl alcohol and benzyl alcohol to produce the corresponding acetate esters, not generated by control flowers. These results strongly point to the dependence of volatile production on substrate availability. Analysis of the diurnal regulation of scent production in rose flowers revealed that although the daily emission of most scent compounds is synchronized, various independently evolved mechanisms control the production, accumulation and release of different volatiles. This research resulted in a fundamental discovery of biochemical pathway, enzymes and genes involved in biosynthesis of C6-C2s compounds, and provided the knowledge for future engineering plants for improved scent quality.
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Crisosto, Carlos, Susan Lurie, Haya Friedman, Ebenezer Ogundiwin, Cameron Peace i George Manganaris. Biological Systems Approach to Developing Mealiness-free Peach and Nectarine Fruit. United States Department of Agriculture, 2007. http://dx.doi.org/10.32747/2007.7592650.bard.
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Peach and nectarine production worldwide is increasing; however consumption is flat or declining because of the inconsistent eating quality experienced by consumers. The main factor for this inconsistent quality is mealiness or woolliness, a form of chilling injury that develops following shipping periods in the global fruit market today. Our research groups have devised various postharvest methods to prolong storage life, including controlled atmosphere and delayed storage; however, these treatments only delay mealiness. Mealiness texture results from disruption of the normal ripening process involving disassembly of cell wall material, and creates a soft fruit texture that is dry and grainy instead of juicy and smooth. Solving this problem is a prerequisite for increasing the demand for fresh peach and nectarine. Two approaches were used to reveal genes and their associated biochemical processes that can confer resistance to mealiness or wooliness. At the Volcani Center, Israel, a nectarine cultivar and the peach cultivar (isogenetic materials) from which the nectarine cultivar spontaneously arose, and at the Kearney Agricultural Center of UC Davis, USA, a peach population that segregates for quantitative resistance to mealiness was used for dissecting the genetic components of mealiness development. During our project we have conducted research integrating the information from phenotypic, biochemical and gene expression studies, proposed possible candidate genes and SNPs-QTLs mapping that are involved in reducing peach mealiness susceptibility. Numerous genes related to ethylene biosynthesis and its signal transduction, cell wall structure and metabolism, stress response, different transcription factor families were detected as being differentially accumulated in the cold-treated samples of these sensitive and less sensitive genotypes. The ability to produce ethylene and keep active genes involved in ethylene signaling, GTP-binding protein, EIN-3 binding protein and an ethylene receptor and activation of ethyleneresponsive fruit ripening genes during cold storage provided greater resistance to CI. Interestingly, in the functional category of genes differentially expressed at harvest, less chilling sensitive cultivar had more genes in categories related to antioxidant and heat sock proteins/chaperones that may help fruit to adapt to low temperature stress. The specific objectives of the proposed research were to: characterize the phenotypes and cell wall components of the two resistant systems in response to mealiness- inducing conditions; identify commonalities and specific differences in cell wall proteins and the transcriptome that are associated with low mealiness incidence; integrate the information from phenotypic, biochemical, and gene expression studies to identify candidate genes that are involved in reducing mealiness susceptibility; locate these genes in the Prunus genome; and associate the genes with genomic regions conferring quantitative genetic variation for mealiness resistance. By doing this we will locate genetic markers for mealiness development, essential tools for selection of mealiness resistant peach lines with improved fruit storability and quality. In our research, QTLs have been located in our peach SNPs map, and proposed candidate genes obtained from the integrated result of phenotypic, biochemical and gene expression analysis are being identified in our QTLs as an approach searching for consistent assistant markers for peach breeding programs.
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Eshed-Williams, Leor, i Daniel Zilberman. Genetic and cellular networks regulating cell fate at the shoot apical meristem. United States Department of Agriculture, styczeń 2014. http://dx.doi.org/10.32747/2014.7699862.bard.
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The shoot apical meristem establishes plant architecture by continuously producing new lateral organs such as leaves, axillary meristems and flowers throughout the plant life cycle. This unique capacity is achieved by a group of self-renewing pluripotent stem cells that give rise to founder cells, which can differentiate into multiple cell and tissue types in response to environmental and developmental cues. Cell fate specification at the shoot apical meristem is programmed primarily by transcription factors acting in a complex gene regulatory network. In this project we proposed to provide significant understanding of meristem maintenance and cell fate specification by studying four transcription factors acting at the meristem. Our original aim was to identify the direct target genes of WUS, STM, KNAT6 and CNA transcription factor in a genome wide scale and the manner by which they regulate their targets. Our goal was to integrate this data into a regulatory model of cell fate specification in the SAM and to identify key genes within the model for further study. We have generated transgenic plants carrying the four TF with two different tags and preformed chromatin Immunoprecipitation (ChIP) assay to identify the TF direct target genes. Due to unforeseen obstacles we have been delayed in achieving this aim but hope to accomplish it soon. Using the GR inducible system, genetic approach and transcriptome analysis [mRNA-seq] we provided a new look at meristem activity and its regulation of morphogenesis and phyllotaxy and propose a coherent framework for the role of many factors acting in meristem development and maintenance. We provided evidence for 3 different mechanisms for the regulation of WUS expression, DNA methylation, a second receptor pathway - the ERECTA receptor and the CNA TF that negatively regulates WUS expression in its own domain, the Organizing Center. We found that once the WUS expression level surpasses a certain threshold it alters cell identity at the periphery of the inflorescence meristem from floral meristem to carpel fate [FM]. When WUS expression highly elevated in the FM, the meristem turn into indeterminate. We showed that WUS activate cytokinine, inhibit auxin response and represses the genes required for root identity fate and that gradual increase in WUCHEL activity leads to gradual meristem enlargement that affect phyllotaxis. We also propose a model in which the direction of WUS domain expansion laterally or upward affects meristem structure differently. We preformed mRNA-seq on meristems with different size and structure followed by k-means clustering and identified groups of genes that are expressed in specific domains at the meristem. We will integrate this data with the ChIP-seq of the 4 TF to add another layer to the genetic network regulating meristem activity.
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Minz, Dror, Stefan J. Green, Noa Sela, Yitzhak Hadar, Janet Jansson i Steven Lindow. Soil and rhizosphere microbiome response to treated waste water irrigation. United States Department of Agriculture, styczeń 2013. http://dx.doi.org/10.32747/2013.7598153.bard.
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Research objectives : Identify genetic potential and community structure of soil and rhizosphere microbial community structure as affected by treated wastewater (TWW) irrigation. This objective was achieved through the examination soil and rhizosphere microbial communities of plants irrigated with fresh water (FW) and TWW. Genomic DNA extracted from soil and rhizosphere samples (Minz laboratory) was processed for DNA-based shotgun metagenome sequencing (Green laboratory). High-throughput bioinformatics was performed to compare both taxonomic and functional gene (and pathway) differences between sample types (treatment and location). Identify metabolic pathways induced or repressed by TWW irrigation. To accomplish this objective, shotgun metatranscriptome (RNA-based) sequencing was performed. Expressed genes and pathways were compared to identify significantly differentially expressed features between rhizosphere communities of plants irrigated with FW and TWW. Identify microbial gene functions and pathways affected by TWW irrigation*. To accomplish this objective, we will perform a metaproteome comparison between rhizosphere communities of plants irrigated with FW and TWW and selected soil microbial activities. Integration and evaluation of microbial community function in relation to its structure and genetic potential, and to infer the in situ physiology and function of microbial communities in soil and rhizospere under FW and TWW irrigation regimes. This objective is ongoing due to the need for extensive bioinformatics analysis. As a result of the capabilities of the new PI, we have also been characterizing the transcriptome of the plant roots as affected by the TWW irrigation and comparing the function of the plants to that of the microbiome. *This original objective was not achieved in the course of this study due to technical issues, especially the need to replace the American PIs during the project. However, the fact we were able to analyze more than one plant system as a result of the abilities of the new American PI strengthened the power of the conclusions derived from studies for the 1ˢᵗ and 2ⁿᵈ objectives. Background: As the world population grows, more urban waste is discharged to the environment, and fresh water sources are being polluted. Developing and industrial countries are increasing the use of wastewater and treated wastewater (TWW) for agriculture practice, thus turning the waste product into a valuable resource. Wastewater supplies a year- round reliable source of nutrient-rich water. Despite continuing enhancements in TWW quality, TWW irrigation can still result in unexplained and undesirable effects on crops. In part, these undesirable effects may be attributed to, among other factors, to the effects of TWW on the plant microbiome. Previous studies, including our own, have presented the TWW effect on soil microbial activity and community composition. To the best of our knowledge, however, no comprehensive study yet has been conducted on the microbial population associated BARD Report - Project 4662 Page 2 of 16 BARD Report - Project 4662 Page 3 of 16 with plant roots irrigated with TWW – a critical information gap. In this work, we characterize the effect of TWW irrigation on root-associated microbial community structure and function by using the most innovative tools available in analyzing bacterial community- a combination of microbial marker gene amplicon sequencing, microbial shotunmetagenomics (DNA-based total community and gene content characterization), microbial metatranscriptomics (RNA-based total community and gene content characterization), and plant host transcriptome response. At the core of this research, a mesocosm experiment was conducted to study and characterize the effect of TWW irrigation on tomato and lettuce plants. A focus of this study was on the plant roots, their associated microbial communities, and on the functional activities of plant root-associated microbial communities. We have found that TWW irrigation changes both the soil and root microbial community composition, and that the shift in the plant root microbiome associated with different irrigation was as significant as the changes caused by the plant host or soil type. The change in microbial community structure was accompanied by changes in the microbial community-wide functional potential (i.e., gene content of the entire microbial community, as determined through shotgun metagenome sequencing). The relative abundance of many genes was significantly different in TWW irrigated root microbiome relative to FW-irrigated root microbial communities. For example, the relative abundance of genes encoding for transporters increased in TWW-irrigated roots increased relative to FW-irrigated roots. Similarly, the relative abundance of genes linked to potassium efflux, respiratory systems and nitrogen metabolism were elevated in TWW irrigated roots when compared to FW-irrigated roots. The increased relative abundance of denitrifying genes in TWW systems relative FW systems, suggests that TWW-irrigated roots are more anaerobic compare to FW irrigated root. These gene functional data are consistent with geochemical measurements made from these systems. Specifically, the TWW irrigated soils had higher pH, total organic compound (TOC), sodium, potassium and electric conductivity values in comparison to FW soils. Thus, the root microbiome genetic functional potential can be correlated with pH, TOC and EC values and these factors must take part in the shaping the root microbiome. The expressed functions, as found by the metatranscriptome analysis, revealed many genes that increase in TWW-irrigated plant root microbial population relative to those in the FW-irrigated plants. The most substantial (and significant) were sodium-proton antiporters and Na(+)-translocatingNADH-quinoneoxidoreductase (NQR). The latter protein uses the cell respiratory machinery to harness redox force and convert the energy for efflux of sodium. As the roots and their microbiomes are exposed to the same environmental conditions, it was previously hypothesized that understanding the soil and rhizospheremicrobiome response will shed light on natural processes in these niches. This study demonstrate how newly available tools can better define complex processes and their downstream consequences, such as irrigation with water from different qualities, and to identify primary cues sensed by the plant host irrigated with TWW. From an agricultural perspective, many common practices are complicated processes with many ‘moving parts’, and are hard to characterize and predict. Multiple edaphic and microbial factors are involved, and these can react to many environmental cues. These complex systems are in turn affected by plant growth and exudation, and associated features such as irrigation, fertilization and use of pesticides. However, the combination of shotgun metagenomics, microbial shotgun metatranscriptomics, plant transcriptomics, and physical measurement of soil characteristics provides a mechanism for integrating data from highly complex agricultural systems to eventually provide for plant physiological response prediction and monitoring. BARD Report
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Gur, Amit, Edward Buckler, Joseph Burger, Yaakov Tadmor i Iftach Klapp. Characterization of genetic variation and yield heterosis in Cucumis melo. United States Department of Agriculture, styczeń 2016. http://dx.doi.org/10.32747/2016.7600047.bard.
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Project objectives: 1) Characterization of variation for yield heterosis in melon using Half-Diallele (HDA) design. 2) Development and implementation of image-based yield phenotyping in melon. 3) Characterization of genetic, epigenetic and transcriptional variation across 25 founder lines and selected hybrids. The epigentic part of this objective was modified during the course of the project: instead of characterization of chromatin structure in a single melon line through genome-wide mapping of nucleosomes using MNase-seq approach, we took advantage of rapid advancements in single-molecule sequencing and shifted the focus to Nanoporelong-read sequencing of all 25 founder lines. This analysis provides invaluable information on genome-wide structural variation across our diversity 4) Integrated analyses and development of prediction models Agricultural heterosis relates to hybrids that outperform their inbred parents for yield. First generation (F1) hybrids are produced in many crop species and it is estimated that heterosis increases yield by 15-30% globally. Melon (Cucumismelo) is an economically important species of The Cucurbitaceae family and is among the most important fleshy fruits for fresh consumption Worldwide. The major goal of this project was to explore the patterns and magnitude of yield heterosis in melon and link it to whole genome sequence variation. A core subset of 25 diverse lines was selected from the Newe-Yaar melon diversity panel for whole-genome re-sequencing (WGS) and test-crosses, to produce structured half-diallele design of 300 F1 hybrids (MelHDA25). Yield variation was measured in replicated yield trials at the whole-plant and at the rootstock levels (through a common-scion grafted experiments), across the F1s and parental lines. As part of this project we also developed an algorithmic pipeline for detection and yield estimation of melons from aerial-images, towards future implementation of such high throughput, cost-effective method for remote yield evaluation in open-field melons. We found extensive, highly heritable root-derived yield variation across the diallele population that was characterized by prominent best-parent heterosis (BPH), where hybrids rootstocks outperformed their parents by 38% and 56 % under optimal irrigation and drought- stress, respectively. Through integration of the genotypic data (~4,000,000 SNPs) and yield analyses we show that root-derived hybrids yield is independent of parental genetic distance. However, we mapped novel root-derived yield QTLs through genome-wide association (GWA) analysis and a multi-QTLs model explained more than 45% of the hybrids yield variation, providing a potential route for marker-assisted hybrid rootstock breeding. Four selected hybrid rootstocks are further studied under multiple scion varieties and their validated positive effect on yield performance is now leading to ongoing evaluation of their commercial potential. On the genomic level, this project resulted in 3 layers of data: 1) whole-genome short-read Illumina sequencing (30X) of the 25 founder lines provided us with 25 genome alignments and high-density melon HapMap that is already shown to be an effective resource for QTL annotation and candidate gene analysis in melon. 2) fast advancements in long-read single-molecule sequencing allowed us to shift focus towards this technology and generate ~50X Nanoporesequencing of the 25 founders which in combination with the short-read data now enable de novo assembly of the 25 genomes that will soon lead to construction of the first melon pan-genome. 3) Transcriptomic (3' RNA-Seq) analysis of several selected hybrids and their parents provide preliminary information on differentially expressed genes that can be further used to explain the root-derived yield variation. Taken together, this project expanded our view on yield heterosis in melon with novel specific insights on root-derived yield heterosis. To our knowledge, thus far this is the largest systematic genetic analysis of rootstock effects on yield heterosis in cucurbits or any other crop plant, and our results are now translated into potential breeding applications. The genomic resources that were developed as part of this project are putting melon in the forefront of genomic research and will continue to be useful tool for the cucurbits community in years to come.