1,926 research outputs found
An overview of the wcd EST clustering tool
No full textHazelhurst S, Hide W, Lipták Z, Nogueira R, Starfield R. An overview of the wcd EST clustering tool. BIOINFORMATICS. 2008;24(13):1542-1546.The wcd system is an open source tool for clustering expressed sequence tags (EST) and other DNA and RNA sequences. wcd allows efficient all-versus-all comparison of ESTs using either the d(2) distance function or edit distance, improving existing implementations of d(2). It supports merging, refinement and reclustering of clusters. It is drop in compatible with the StackPack clustering package. wcd supports parallelization under both shared memory and cluster architectures. It is distributed with an EMBOSS wrapper allowing wcd to be installed as part of an EMBOSS installation (and so provided by a web server)
Muriel Spark as auto-biographer in <i>Curriculum</i> <i>Vitae</i>
No full textExamining Muriel Spark's main aims as an auto-biographer in her work Curriculum Vitae brings important resources in the exploration of the genre of autobiographical writing. This with the theoretical engagement, allows consideration of the critical issues surrounding the roles of author and reader in the construction of the literary self. Spark demands the reader participate in the constructon of textual meaning; overturning the conventions of autobiography, satirising its claims to omniscience and highlighting the impossibility of an authentic voice with regard to the self
Low detection of exon skipping in mouse genes orthologous to human genes on chromosome 22
No full textMagister Scientiae - MSc (Biochemistry)Alternative RNA splicing is one of the leading mechanisms contributing towards transcript and protein diversity. Several alternative splicing surveys have confirmed the frequent occurrence of exon skipping in human genes. However, the occurrence of exon skipping in mouse genes has not yet been extensively examined. Recent improvements in mouse genome sequencing have permitted the current study to explore the occurrence of exon skipping in mouse genes orthologous to human genes on chromosome 22. A low number (5/72 multi-exon genes) of mouse exon-skipped genes were captured through alignments of mouse ESTs to mouse genomic contigs. Exon-skipping events in two mouse exon-skipped genes (GNB1L, SMARCB1) appear to affect biological processes such as electron and protein transport. All mouse, skipped exons were observed to have ubiquitous tissue expression. Comparison of our mouse exon-skipping events to previously detected human exon-skipping events on chromosome 22 by Hide et al.2001, has revealed that mouse and human exon-skipping events were never observed together within an orthologous gene-pair. Although the transcript identity between mouse and human orthologous transcripts were high (greater than 80% sequence identity), the exon order in these gene-pairs may be different between mouse and human orthologous genes. Main factors contributing towards the low detection of mouse exon-skipping events include the lack of mouse transcripts matching to mouse genomic sequences and the under-prediction of mouse exons. These factors resulted in a large number (112/269) of mouse transcripts lacking matches to mouse genomic contigs and nearly half (12/25) of the mouse multi-exon genes, which have matching Ensembl transcript identifiers, have under-predicted exons. The low frequency of mouse exon skipping on chromosome 22 cannot be extrapolated to represent a genome-wide estimate due to the small number of observed mouse exon-skipping events. However, when compared to a higher estimate (52/347) of exon skipping in human genes for chromosome 22 produced under similar conditions by Hide et al.2001, it is possible that our mouse exon-skipping frequency may be lower than the human frequency. Our hypothesis contradicts with a previous study by Brett et al.2002, in which the authors claim that mouse and human alternative splicing is comparable. Our conclusion that the mouse exon-skipping frequency may be lower than the human estimate remains to be tested with a larger mouse multi-exon gene set. However, the mouse exon-skipping frequency may represent the highest estimate that can be obtained given that the current number (87) of mouse genes orthologous to chromosome 22 in Ensembl (v1 30th Jan. 2002) does not deviate significantly from our total number (72) of mouse multi-exon genes. The quality of the current mouse genomic data is higher than the one utilized in this study. The capture of mouse exon-skipping events may increase as the quality and quantity of mouse genomic and transcript sequences improves.South Afric
Low detection of exon skipping in mouse genes orthologous to human genes on chromosome 22
No full textMagister Scientiae - MSc (Biochemistry)Alternative RNA splicing is one of the leading mechanisms contributing towards transcript and protein diversity. Several alternative splicing surveys have confirmed the frequent occurrence of exon skipping in human genes. However, the occurrence of exon skipping in mouse genes has not yet been extensively examined. Recent improvements in mouse genome sequencing have permitted the current study to explore the occurrence of exon skipping in mouse genes orthologous to human genes on chromosome 22. A low number (5/72 multi-exon genes) of mouse exon-skipped genes were captured through alignments of mouse ESTs to mouse genomic contigs. Exon-skipping events in two mouse exon-skipped genes (GNB1L, SMARCB1) appear to affect biological processes such as electron and protein transport. All mouse, skipped exons were observed to have ubiquitous tissue expression. Comparison of our mouse exon-skipping events to previously detected human exon-skipping events on chromosome 22 by Hide et al.2001, has revealed that mouse and human exon-skipping events were never observed together within an orthologous gene-pair. Although the transcript identity between mouse and human orthologous transcripts were high (greater than 80% sequence identity), the exon order in these gene-pairs may be different between mouse and human orthologous genes. Main factors contributing towards the low detection of mouse exon-skipping events include the lack of mouse transcripts matching to mouse genomic sequences and the under-prediction of mouse exons. These factors resulted in a large number (112/269) of mouse transcripts lacking matches to mouse genomic contigs and nearly half (12/25) of the mouse multi-exon genes, which have matching Ensembl transcript identifiers, have under-predicted exons. The low frequency of mouse exon skipping on chromosome 22 cannot be extrapolated to represent a genome-wide estimate due to the small number of observed mouse exon-skipping events. However, when compared to a higher estimate (52/347) of exon skipping in human genes for chromosome 22 produced under similar conditions by Hide et al.2001, it is possible that our mouse exon-skipping frequency may be lower than the human frequency. Our hypothesis contradicts with a previous study by Brett et al.2002, in which the authors claim that mouse and human alternative splicing is comparable. Our conclusion that the mouse exon-skipping frequency may be lower than the human estimate remains to be tested with a larger mouse multi-exon gene set. However, the mouse exon-skipping frequency may represent the highest estimate that can be obtained given that the current number (87) of mouse genes orthologous to chromosome 22 in Ensembl (v1 30th Jan. 2002) does not deviate significantly from our total number (72) of mouse multi-exon genes. The quality of the current mouse genomic data is higher than the one utilized in this study. The capture of mouse exon-skipping events may increase as the quality and quantity of mouse genomic and transcript sequences improves.South Afric
New Algorithms for EST clustering
No full textPhilosophiae Doctor - PhDExpressed sequence tag database is a rich and fast growing source of data for gene expression analysis and drug discovery. Clustering of raw EST data is a necessary step for further analysis and one of the most challenging problems of modem computational biology. There are a few systems, designed for this purpose and a few more are currently under development. These systems are reviewed in the "Literature
and software review". Different strategies of supervised and unsupervised clustering are discussed, as well as sequence comparison techniques, such as based on alignment or oligonucleotide compositions. Analysis of potential bottlenecks and estimation of computation complexity of EST clustering is done in Chapter 2. This chapter also states the goals for the research and justifies the need for new algorithm that has to be fast, but still sensitive to relatively short (40 bp) regions of local similarity. A new sequence comparison algorithm is developed and described in Chapter 3. This algorithm has a linear computation complexity and sufficient sensitivity to detect short regions of local similarity between nucleotide sequences. The algorithm utilizes an asymmetric approach, when one of the compared sequences is presented in a form of oligonucleotide table, while the second sequence is in standard, linear form. A short window is moved along the linear sequence and all overlapping oligonucleotides of a constant length in the frame are compared for the oligonucleotide table. The result of comparison of two sequences is a single figure, which can be compared to a threshold. For each measure of sequence similarity a probability of false positive and false negative can be estimated. The algorithm was set up and implemented to recognize matching ESTs with overlapping regions of 40bp with 95% identity, which is better than resolution ability of contemporary EST clustering tools This algorithm was used as a sequence comparison engine for two EST clustering programs, described in Chapter 4. These programs implement two different strategies:
stringent and loose clustering. Both are tested on small, but realistic benchmark data sets and show the results, similar to one of the best existing clustering programs, 02_cluster, but with a significant advantage in speed and sensitivity to small overlapping regions of ESTs. On three different CPUs the new algorithm run at least two times faster, leaving less singletons and producing bigger clusters. With parallel
optimization this algorithm is capable of clustering millions of ESTs on relatively inexpensive computers. The loose clustering variant is a highly portable application, relying on third-party software for cluster assembly. It was built to the same specifications as 02_ cluster and can be immediately included into the STACKPack package for EST clustering. The stringent clustering program produces already
assembled clusters and can apprehend alternatively processed variants during the clustering process
Ancient Genes in Cancer Gene Expression?
No full text>Magister Scientiae - MScBacksround: The Cancer/testis (CT) antigens are a division of germ cell specific genes not expressed in somatic cells, exceptions being placental cells and 20Vo - 4OVo of cancer types. The aptitude of CT antigens to elicit humoral immune responses, their restricted expression profile, absence of major histocompatability complex expression in male germline cells have contributed to the emergent attraction of CT antigens as ideal, prospective cancer vaccination candidates. Motivation: Presently there are M CT gene families containing a total of 97 gene products and isoforms. Due to the promulgation in sensitivity and specificity of rapid serological immunodetection assays e.g. serial analysis of recombinant cDNA expression libraries (SEREX), the magnitude of novel CT genes and gene families will increase. Hence, characteization of this unique subset of CT genes is fundamental to our erudition of this rapidly emerging novel subset of genes.
Obiectives: The sequencing of the human genome provides a useful biological framework for the categoization and systematization of rapidly accumulating biological information. A genomic approach was used to ascertain the locations of the CT genes in the human genome and determine if the genomic locations of the CT genes is nonrandom. An in-silico expression study was conducted for the CT genes with the aim of establishing if CT gene expression is restricted to the testis. A portion of the human genome housing the largest proportion of the CT genes was selected for analysis in order to determine if the surrounding genomic architecture influences CT gene expression. A comparative genomics approach was used in determining if the CT genes are "ancient genes
Fiander, Winston. Interview about Play and Games during his childhood in Coomb's Cove, Fortune Bay
No full textRounders; Location of Coomb's Cove; Sliding; Hide and seek; Model sailboat racing; Rowing and sailing his punt; Rescue of a fisherman; Dories; Bicycles; Swimming; Playing outdoors; Snow houses; Pedlar Joe (piddly); Slingshots; Breaking the neighbour's window; Tokens; Ice hockey; Making hockey sticks. Phone interview
"Development and implementation of ontology-based systems for mammalian gene expression profiling"
No full textPhilosophiae Doctor - PhDThe use of ontologies in the mapping of gene expression events provides an effective and comparable method to determine the expression profile of an entire genome across a large collection of experiments derived from different expression sources. In this dissertation I describe the development of the developmental human and mouse e VOC ontologies and demonstrate the ontologies by identifying genes showing a bias for developmental brain expression in human and mouse, identifying transcription factor complexes, and exploring the mouse orthologs of human cancer/testis genes. Model organisms represents fundamental aspects of mammal biology phenomena between model organism
is complex and it is to be the meaningful, a simplified representation can be a powerful means for comparison illustrated here in two ways.
Firstly, the ontologies have been used to illustrate methods to determine clusters of genes showing tissue-restricted expression in humans. The identification of tissue-restricted genes within an organism serves as an indication of the finetuning in the regulation of gene expression in a given tissue. Secondly, due to the differences in human and mouse gene expression on a temporal and spatial level, the ontologies were used to identify mouse orthologs of human cancer/testis genes showing cancer/testis characteristics. With the use of model systems such as
mouse in the development of gene-targeted drugs in the treatment of disease, it is important to establish that the expression characteristics and profiles of a drug target in the model system is representative of the characteristics of the target in the system for which it is intended
Development and implementation of ontology-based systems for mammalian gene expression profiling
No full textPhilosophiae Doctor - PhDThe use of ontologies in the mapping of gene expression events provides an
effective and comparable method to determine the expression profile of an entire
genome across a large collection of experiments derived from different expression
sources. In this dissertation I describe the development of the developmental
human and mouse eVOC ontologies and demonstrate the ontologies by identifying genes showing a bias for developmental brain expression in human and mouse, identifying transcription factor complexes, and exploring the mouse orthologs of human cancer/testis genes.Model organisms represent an important resource for understanding the fundamental aspects of mammalian biology. Mapping of biological phenomena between model organisms is complex and if it is to be meaningful, a simplified representation can be a powerful means for comparison.
The implementation of the ontologies has been illustrated here in two ways.Firstly, the ontologies have been used to illustrate methods to determine clusters of genes showing tissue-restricted expression in humans. The identification of tissue restricted genes within an organism serves as an indication of the finetuning in the regulation of gene expression in a given tissue. Secondly, due to the differences in human and mouse gene expression on a temporal and spatial level, the ontologies were used to identify mouse orthologs of human cancer/testis genes showing cancer/testis characteristics. With the use of model systems such as mouse in the development of gene-targeted drugs in the treatment of disease, it is important to establish that the expression characteristics and profiles of a drug target in the model system is representative of the characteristics of the target in the system for which it is intended
Development and implementation of ontology-based systems for mammalian gene expression profiling
No full textPhilosophiae Doctor - PhDThe use of ontologies in the mapping of gene expression events provides an
effective and comparable method to determine the expression profile of an entire
genome across a large collection of experiments derived from different expression
sources. In this dissertation I describe the development of the developmental
human and mouse eVOC ontologies and demonstrate the ontologies by identifying genes showing a bias for developmental brain expression in human and mouse, identifying transcription factor complexes, and exploring the mouse orthologs of human cancer/testis genes.Model organisms represent an important resource for understanding the fundamental aspects of mammalian biology. Mapping of biological phenomena between model organisms is complex and if it is to be meaningful, a simplified representation can be a powerful means for comparison.
The implementation of the ontologies has been illustrated here in two ways.Firstly, the ontologies have been used to illustrate methods to determine clusters of genes showing tissue-restricted expression in humans. The identification of tissue restricted genes within an organism serves as an indication of the finetuning in the regulation of gene expression in a given tissue. Secondly, due to the differences in human and mouse gene expression on a temporal and spatial level, the ontologies were used to identify mouse orthologs of human cancer/testis genes showing cancer/testis characteristics. With the use of model systems such as mouse in the development of gene-targeted drugs in the treatment of disease, it is important to establish that the expression characteristics and profiles of a drug target in the model system is representative of the characteristics of the target in the system for which it is intended
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