Author: Charles W. SugnetPublisher:
ISBN:
Category :
Languages : en
Pages : 288
Book Description
Discovery and Detection of Alternative Splicing
Author: Charles W. SugnetStatistical Methods for Alternative Splicing Using RNA Sequencing
Author: Yu HuPublisher:
ISBN:
Category :
Languages : en
Pages : 0
Book Description
The emergence of RNA-seq technology has made it possible to estimate isoform-specific gene expression and detect differential alternative splicing between conditions, thus providing us an effective way to discover disease susceptibility genes. Analysis of alternative splicing, however, is challenging because various biases present in RNA-seq data complicates the analysis, and if not appropriately corrected, will affect gene expression estimation and downstream modeling. Motivated by these issues, my dissertation focused on statistical problems related to the analysis of alternative splicing in RNA-seq data. In Part I of my dissertation, I developed PennSeq, a method that aims to account for non-uniform read distribution in isoform expression estimation. PennSeq models non-uniformity using the empirical read distribution in RNA-seq data. It is the first time that non-uniformity is modeled at the isoform level. Compared to existing approaches, PennSeq allows bias correction at a much finer scale and achieved higher estimation accuracy. In Part II of my dissertation, I developed PennDiff, a method that aims to detect differential alternative splicing by RNA-seq. This approach avoids multiple testing for exons originated from the same isoform(s) and is able to detect differential alternative splicing at both exon and gene level, with more flexibility and higher sensitivity than existing methods. In Part III of my dissertation, I focused on problems arising from single-cell RNA-seq (scRNA-seq), a newly developed technology that allows the measurement of cellular heterogeneity of gene expression in single cells. Compared to bulk tissue RNA-seq, analysis of scRNA-seq data is more challenging due to high technical variability across cells and extremely low sequencing depth. To overcome these challenges, I developed SCATS, a method that aims to detect differential alternative splicing with scRNA-seq data. SCATS employs an empirical Bayes approach to model technical noise by use of external RNA spike-ins and groups informative reads sharing the same isoform(s) to detect splicing change. SCATS showed superior performance in both simulation and real data analyses. In summary, methods developed in my dissertation provide biomedical researchers a set of powerful tools for transcriptomic data analysis and will aid novel scientific discovery.
RNA Biochemistry and Biotechnology
Author: Jan BarciszewskiPublisher: Springer Science & Business Media
ISBN: 9401144850
Category : Science
Languages : en
Pages : 373
Book Description
RNA Biochemistry and Biotechnology describes various aspects of nucleic acid and protein structure, mainly RNA structure and proteins, interacting with specific RNA species. Papers deal with DNA protein interactions, telomerase, aminoacyl-tRNA synthetases, elongation factor Tu, DNA repair, RNA structure, NMR technology, RNA aptamer interaction of biological macromolecules with metal ions. Two papers deal with theoretical aspects of RNA structure production and computer modelling. Many papers describe the possibility of commercial application of RNA biotechnology. One article discusses the impact of direct democracy on basic science supporting biotechnology. Readership: Advanced graduate students, Ph.D. students and young scientists as well as specialists in the field.
Regulation of Alternative Splicing
Author: Philippe JeanteurPublisher: Springer Science & Business Media
ISBN: 3662097281
Category : Science
Languages : en
Pages : 254
Book Description
The discovery in 1977 that genes are split into exons and introns has done away with the one gene - one protein dogma. Indeed, the removal of introns from the primary RNA transcript is not necessarily straightforward since there may be optional pathways leading to different messenger RNAs and consequently to different proteins. Examples of such an alternative splicing mechanism cover all fields of biology. Moreover, there are plenty of occurrences where deviant splicing can have pathological effects. Despite the high number of specific cases of alternative splicing, it was not until recently that the generality and extent of this phenomenon was fully appreciated. A superficial reading of the preliminary sequence of the human genome published in 2001 led to the surprising, and even deceiving to many scientists, low number of genes (around 32,000) which contrasted with the much higher figure around 150,000 which was previously envisioned. Attempts to make a global assessment of the use of alternative splicing are recent and rely essentially on the comparison of genomic mRNA and EST sequences as reviewed by Thanaraj and Stamm in the first chapter of this volume. Most recent estimates suggest that 40-60% of human genes might be alternatively spliced, as opposed to about 22% for C. elegans.
Proceedings of the Twelfth Annual ACM-SIAM Symposium on Discrete Algorithms
Author: SIAM Activity Group on Discrete MathematicsPublisher: SIAM
ISBN: 9780898714906
Category : Mathematics
Languages : en
Pages : 962
Book Description
Contains 130 papers, which were selected based on originality, technical contribution, and relevance. Although the papers were not formally refereed, every attempt was made to verify the main claims. It is expected that most will appear in more complete form in scientific journals. The proceedings also includes the paper presented by invited plenary speaker Ronald Graham, as well as a portion of the papers presented by invited plenary speakers Udi Manber and Christos Papadimitriou.
Alternative Splicing and Disease
Author: Philippe JeanteurPublisher: Springer Science & Business Media
ISBN: 3540344497
Category : Science
Languages : en
Pages : 265
Book Description
Splicing of primary RNA transcript is a quasi-systematic step of gene expression in higher organisms. This is the first book to highlight the medical implications, i.e. diseases, caused by alternative splicing. Alternative splicing not only vastly increases protein diversity but also offers numerous opportunities for aberrant splicing events with pathological consequences. The book also outlines possible targets for therapy.
Global Analyses of Alternative Splicing in Evolution and Nervous System Development
Author: John Anthony CalarcoPublisher:
ISBN: 9780494781418
Category :
Languages : en
Pages : 460
Book Description
Technological advancements have sparked discovery in biology, enabling important questions to be addressed experimentally at unprecedented depth and scale. One such advance, the development of large-scale approaches to study gene expression, has transformed the way we view the transcriptome. In recent years, these approaches have been applied to studies of alternative RNA splicing, a process where multiple distinct messenger RNAs can be generated from precursor transcripts to produce extensive transcriptomic diversity from a limited repertoire of genes. Global analyses have not only reinforced models initially based on single gene studies, they have also led to numerous insights into general principles governing the regulation and evolution of alternative splicing. In this thesis, I describe how I have combined both large-scale and focused approaches to study alternative splicing regulation during development and in an evolutionary context. Using microarray profiling and comparative genomics approaches, I describe the first large-scale comparative analysis of alternative splicing patterns between humans and chimpanzees. Next, I describe the discovery of a novel neural-specific RS domain splicing factor and the network of alternative exons it regulates to promote nervous system development in vertebrates. Finally, I describe the profiling of alternative splicing patterns during C. elegans development using splicing microarrays and high-throughput sequencing. In this latter study, I also describe two resources that facilitate the analysis of tissue- or cell type-specific splicing events, and enable the function of isoforms to be assessed in vivo . Collectively, these studies have shed light on how differential regulation of alternative splicing has contributed to the evolution of complexity and diversity in biological systems.
Bioinformatics in Rice Research
Author: Manoj Kumar GuptaPublisher: Springer Nature
ISBN: 9811639930
Category : Science
Languages : en
Pages : 609
Book Description
This book provides an up-to-date review of classic and advanced bioinformatics approaches and their utility in rice research. It summarizes databases and tools for analyzing DNA, proteins and gene expression profiles, mapping genetic variations, annotation of protein and RNA molecules, phylogenetic analysis, and pathway enrichment. In addition, it presents high-throughput technologies that are widely used to provide deep insights into the genetic architecture of important traits in the rice genome. The book subsequently discusses techniques for identifying RNA-protein, DNA-protein interactions, and molecular markers, including SNP and microsatellites, in the contexts of rice breeding and genetics. Lastly, it explores various tools that are used to identify and characterize non-coding RNA in rice and their potential role in rice research.
Evolution of Translational Omics
Author: Institute of MedicinePublisher: National Academies Press
ISBN: 0309224187
Category : Science
Languages : en
Pages : 354
Book Description
Technologies collectively called omics enable simultaneous measurement of an enormous number of biomolecules; for example, genomics investigates thousands of DNA sequences, and proteomics examines large numbers of proteins. Scientists are using these technologies to develop innovative tests to detect disease and to predict a patient's likelihood of responding to specific drugs. Following a recent case involving premature use of omics-based tests in cancer clinical trials at Duke University, the NCI requested that the IOM establish a committee to recommend ways to strengthen omics-based test development and evaluation. This report identifies best practices to enhance development, evaluation, and translation of omics-based tests while simultaneously reinforcing steps to ensure that these tests are appropriately assessed for scientific validity before they are used to guide patient treatment in clinical trials.
Technology and Method Developments for High-throughput Translational Medicine
Author: Junhee SeokPublisher: Stanford University
ISBN:
Category :
Languages : en
Pages : 122
Book Description
Translation of knowledge from basic science to medicine is essential to improving both clinical research and practice. In this translation, high-throughput genomic approaches can greatly accelerate our understanding of molecular mechanisms of diseases. A successful high-throughput genomic study of disease requires, first, comprehensive and efficient platforms to collect genomic data from clinical samples, and second, computational analysis methods that utilize databases of prior biological knowledge together with experimental data to derive clinically meaningful results. In this thesis, we discuss the development of a new microarray platform as well as computational methods for knowledge-based analysis along with their applications in clinical research. First, we and other colleagues have developed a new high-density oligonucleo-tide array of the human transcriptome for high-throughput and cost-efficient analysis of patient samples in clinical studies. This array allows comprehensive examination of gene expression and genome-wide identification of alternative splicing, and also pro-vides assays for coding SNP detection and non-coding transcripts. Compared with high-throughput mRNA sequencing technology, we show that this array is highly re-producible in estimating gene and exon expression, and sensitive in detecting expres-sion changes. In addition, the exon-exon junction feature of this array is shown to im-prove detection efficiency for mRNA alternative splicing when combined with an ap-propriate computational method. We implemented the use of this array in a multi-center clinical program and have obtained comparable levels of high quality and re-producible data. With low costs and high throughputs for sample processing, we antic-ipate that this array platform will have a wide range of applications in high-throughput clinical studies. Second, we investigated knowledge-based methods that utilize prior know-ledge from biology and medicine to improve analysis and interpretation of high-throughput genomic data. We have developed knowledge-based methods to enrich our prior knowledge, illustrate dynamic response to external stimulus, and identify distur-bances in cellular pathways by chemical exposure, as well as discover hidden biological signatures for the prediction of patient outcomes. Finally, we applied a knowledge-based approach in a large scale genomic study of trauma patients. Cooperating with clinical information, prior knowledge improved the interpretation of common and dif-ferential genomic response to injury, and provided efficient risk assessment for patient outcomes. The clinical and genomic data as well as analysis results in this trauma study were systematically organized and provided to research communities as new knowledge of traumatic injury. The microarray platform and knowledge-based methods presented in this thesis provide appropriate research tools for high-throughput translational medicine in a large clinical setting. This thesis is expected to advance understanding and treatment for dis-eases, and finally, improve public health.