Analysis of predictive power of binding affinity of PBM-derived sequences
- Authors: Matereke, Lavious Tapiwa
- Date: 2015
- Subjects: Transcription factors , Protein binding , DNA-binding proteins , Chromatin , Protein microarrays
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4161 , http://hdl.handle.net/10962/d1018666
- Description: A transcription factor (TF) is a protein that binds to specific DNA sequences as part of the initiation stage of transcription. Various methods of finding these transcription factor binding sites (TFBS) have been developed. In vivo technologies analyze DNA binding regions known to have bound to a TF in a living cell. Most widely used in vivo methods at the moment are chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) and DNase I hypersensitive sites sequencing. In vitro methods derive TFBS based on experiments with TFs and DNA usually in artificial settings or computationally. An example is the Protein Binding Microarray which uses artificially constructed DNA sequences to determine the short sequences that are most likely to bind to a TF. The major drawback of this approach is that binding of TFs in vivo is also dependent on other factors such as chromatin accessibility and the presence of cofactors. Therefore TFBS derived from the PBM technique might not resemble the true DNA binding sequences. In this work, we use PBM data from the UniPROBE motif database, ChIP-seq data and DNase I hypersensitive sites data. Using the Spearman’s rank correlation and area under receiver operating characteristic curve, we compare the enrichment scores which the PBM approach assigns to its identified sequences and the frequency of these sequences in likely binding regions and the human genome as a whole. We also use central motif enrichment analysis (CentriMo) to compare the enrichment of UniPROBE motifs with in vivo derived motifs (from the JASPAR CORE database) in their respective TF ChIP-seq peak region. CentriMo is applied to 14 TF ChIP-seq peak regions from different cell lines. We aim to establish if there is a relationship between the occurrences of UniPROBE 8-mer patterns in likely binding regions and their enrichment score and how well the in vitro derived motifs match in vivo binding specificity. We did not come out with a particular trend showing failure of the PBM approach to predict in vivo binding specificity. Our results show Ets1, Hnf4a and Tcf3 show prediction failure by the PBM technique in terms of our Spearman’s rank correlation for ChIP-seq data and central motif enrichment analysis. However, the PBM technique also matched the in vivo binding specificities of FoxA2, Pou2f2 and Mafk. Failure of the PBM approach was found to be a result of variability in the TF’s binding specificity, the presence of cofactors, narrow binding specificity and the presence ubiquitous binding patterns.
- Full Text:
- Date Issued: 2015
- Authors: Matereke, Lavious Tapiwa
- Date: 2015
- Subjects: Transcription factors , Protein binding , DNA-binding proteins , Chromatin , Protein microarrays
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4161 , http://hdl.handle.net/10962/d1018666
- Description: A transcription factor (TF) is a protein that binds to specific DNA sequences as part of the initiation stage of transcription. Various methods of finding these transcription factor binding sites (TFBS) have been developed. In vivo technologies analyze DNA binding regions known to have bound to a TF in a living cell. Most widely used in vivo methods at the moment are chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) and DNase I hypersensitive sites sequencing. In vitro methods derive TFBS based on experiments with TFs and DNA usually in artificial settings or computationally. An example is the Protein Binding Microarray which uses artificially constructed DNA sequences to determine the short sequences that are most likely to bind to a TF. The major drawback of this approach is that binding of TFs in vivo is also dependent on other factors such as chromatin accessibility and the presence of cofactors. Therefore TFBS derived from the PBM technique might not resemble the true DNA binding sequences. In this work, we use PBM data from the UniPROBE motif database, ChIP-seq data and DNase I hypersensitive sites data. Using the Spearman’s rank correlation and area under receiver operating characteristic curve, we compare the enrichment scores which the PBM approach assigns to its identified sequences and the frequency of these sequences in likely binding regions and the human genome as a whole. We also use central motif enrichment analysis (CentriMo) to compare the enrichment of UniPROBE motifs with in vivo derived motifs (from the JASPAR CORE database) in their respective TF ChIP-seq peak region. CentriMo is applied to 14 TF ChIP-seq peak regions from different cell lines. We aim to establish if there is a relationship between the occurrences of UniPROBE 8-mer patterns in likely binding regions and their enrichment score and how well the in vitro derived motifs match in vivo binding specificity. We did not come out with a particular trend showing failure of the PBM approach to predict in vivo binding specificity. Our results show Ets1, Hnf4a and Tcf3 show prediction failure by the PBM technique in terms of our Spearman’s rank correlation for ChIP-seq data and central motif enrichment analysis. However, the PBM technique also matched the in vivo binding specificities of FoxA2, Pou2f2 and Mafk. Failure of the PBM approach was found to be a result of variability in the TF’s binding specificity, the presence of cofactors, narrow binding specificity and the presence ubiquitous binding patterns.
- Full Text:
- Date Issued: 2015
Spatial and temporal occurrence of forensically important South African blowflies (Diptera: Calliphorida)
- Authors: Williams, Kirstin Alexa
- Date: 2003
- Subjects: Blowflies -- South Africa , Forensic entomology
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:5617 , http://hdl.handle.net/10962/d1003217 , Blowflies -- South Africa , Forensic entomology
- Description: Forensic entomology is an emergjng field in South Africa. Little is known about South African blowflies and factors that affect their use in a forensic context. This work provides a review and synthesis of previous work in South Africa and supplements some of the background and basic knowledge required for forensic entomology in South Africa. The seasonal occurrence of eight forensicaIIy important blowfly species was quantified by fortnightly trapping in Grahamstown, South Africa. The spatial distribution of each species was related to seasonal occurrence and habitat preference. Seasonal distributions of blowflies in carcasses in South Africa were obtained from the literature and compared to the seasonal trapping. By mapping South African locality records of forensicaIIy important blowflies and analyzing these records in a modified Principal Components Analysis of climatic data, the potential geographic distributions of each fly species was modeIIed. Most species were widespread, but Calliphora croceipalpis, Jaennicke, 1867, was found in cold places. This information is important for determining where certain species are likely to occur in forensic investigations. Nocturnal oviposition was examined in both field and laboratory experiments. Lucilia species could oviposit nocturnaIIy in the field, while Lucilia species, Chrysomya chloropyga, (Weidemann, 1818) and C. putoria (Weidemann, 1830) could oviposit nocturnaIIy in the laboratory. These findings are important factors in affecting the precision of estimates of a post mortem interval (PM!) by up to 12 hours. The thermophysiological ranges of four species of adult blowflies were determined by measuring onset temperatures of four significant behaviours: onset of neural activity; onset of coordinated movement; shade-seeking and death. There was a sexual size dimorphism in Lucilia species, Chrysomya chloropyga and Calliphora croceipalpis with females being larger than males. Chrysomya megacephala (Fabricius, 1794) had an unexpectedly high death threshold, while Calliphora croceipalpis had the lowest death threshold of the flies tested. These points were related to the seasonal and geographic occurrence of each species, to nocturnal activity and placed in a forensic context.
- Full Text:
- Date Issued: 2003
- Authors: Williams, Kirstin Alexa
- Date: 2003
- Subjects: Blowflies -- South Africa , Forensic entomology
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:5617 , http://hdl.handle.net/10962/d1003217 , Blowflies -- South Africa , Forensic entomology
- Description: Forensic entomology is an emergjng field in South Africa. Little is known about South African blowflies and factors that affect their use in a forensic context. This work provides a review and synthesis of previous work in South Africa and supplements some of the background and basic knowledge required for forensic entomology in South Africa. The seasonal occurrence of eight forensicaIIy important blowfly species was quantified by fortnightly trapping in Grahamstown, South Africa. The spatial distribution of each species was related to seasonal occurrence and habitat preference. Seasonal distributions of blowflies in carcasses in South Africa were obtained from the literature and compared to the seasonal trapping. By mapping South African locality records of forensicaIIy important blowflies and analyzing these records in a modified Principal Components Analysis of climatic data, the potential geographic distributions of each fly species was modeIIed. Most species were widespread, but Calliphora croceipalpis, Jaennicke, 1867, was found in cold places. This information is important for determining where certain species are likely to occur in forensic investigations. Nocturnal oviposition was examined in both field and laboratory experiments. Lucilia species could oviposit nocturnaIIy in the field, while Lucilia species, Chrysomya chloropyga, (Weidemann, 1818) and C. putoria (Weidemann, 1830) could oviposit nocturnaIIy in the laboratory. These findings are important factors in affecting the precision of estimates of a post mortem interval (PM!) by up to 12 hours. The thermophysiological ranges of four species of adult blowflies were determined by measuring onset temperatures of four significant behaviours: onset of neural activity; onset of coordinated movement; shade-seeking and death. There was a sexual size dimorphism in Lucilia species, Chrysomya chloropyga and Calliphora croceipalpis with females being larger than males. Chrysomya megacephala (Fabricius, 1794) had an unexpectedly high death threshold, while Calliphora croceipalpis had the lowest death threshold of the flies tested. These points were related to the seasonal and geographic occurrence of each species, to nocturnal activity and placed in a forensic context.
- Full Text:
- Date Issued: 2003
The effect of energy and protein nutritional levels on production of breeding ostriches
- Authors: Brand, Zanell
- Date: 2002
- Subjects: Ostriches -- Nutrition , Ostriches -- Breeding--South Africa
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:5805 , http://hdl.handle.net/10962/d1006312 , Ostriches -- Nutrition , Ostriches -- Breeding--South Africa
- Description: Adequate and appropriate nutrition is essential for the production of high quality commercially farmed animal species. Although South Africa has had a well-established ostrich industry for over a century, little information on ostrich nutrition, in particular the specific nutritional requirements at different stages of production, is available. The industry has consequently relied heavily on data derived from poultry and pigs, but this has often proved to be unsatisfactory for ostriches and has resulted in serious nutritional-related problems. Recent studies on the metabolisable energy of specific components of diet formulations and balanced diets have indicated that ostriches have enhanced digestibility compared with poultry and pigs. At the same time, in the present economic climate, it is necessary to find cost-effective diets for breeding birds without compromising egg and chick production. This study primarily assessed the effect of different dietary protein and energy levels on production parameters and body condition of breeding female and male ostriches. The energy content of the diet appears to be the main constraint to egg production and breeders on low energy diets laid fewer eggs and lost more body condition compared with breeders fed higher energy diets. A diet with 8.5 MJ/kg DM and 10% protein with well balanced amino acids appears to be sufficient for female breeders without compromising production and a diet with 7.5 MJ/kg DM and 10% protein appears suitable for breeding male ostriches. Different dietary energy and protein levels similarly had little or no effect on egg quality and composition. This study also assessed the carry-over effect of the nutritional regime in one year on the production in the following breeding season. Females fed diets as low as 7.5 MJ/kg ME in the previous breeding season produced significantly fewer eggs in the next breeding season, which resulted in lower chick production. Energy had no effect on the percentage infertile eggs or on the initial egg weight. Different levels of dietary protein had no effect on egg production, egg weight, fertility, hatchability and initial chick weight.
- Full Text:
- Date Issued: 2002
- Authors: Brand, Zanell
- Date: 2002
- Subjects: Ostriches -- Nutrition , Ostriches -- Breeding--South Africa
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:5805 , http://hdl.handle.net/10962/d1006312 , Ostriches -- Nutrition , Ostriches -- Breeding--South Africa
- Description: Adequate and appropriate nutrition is essential for the production of high quality commercially farmed animal species. Although South Africa has had a well-established ostrich industry for over a century, little information on ostrich nutrition, in particular the specific nutritional requirements at different stages of production, is available. The industry has consequently relied heavily on data derived from poultry and pigs, but this has often proved to be unsatisfactory for ostriches and has resulted in serious nutritional-related problems. Recent studies on the metabolisable energy of specific components of diet formulations and balanced diets have indicated that ostriches have enhanced digestibility compared with poultry and pigs. At the same time, in the present economic climate, it is necessary to find cost-effective diets for breeding birds without compromising egg and chick production. This study primarily assessed the effect of different dietary protein and energy levels on production parameters and body condition of breeding female and male ostriches. The energy content of the diet appears to be the main constraint to egg production and breeders on low energy diets laid fewer eggs and lost more body condition compared with breeders fed higher energy diets. A diet with 8.5 MJ/kg DM and 10% protein with well balanced amino acids appears to be sufficient for female breeders without compromising production and a diet with 7.5 MJ/kg DM and 10% protein appears suitable for breeding male ostriches. Different dietary energy and protein levels similarly had little or no effect on egg quality and composition. This study also assessed the carry-over effect of the nutritional regime in one year on the production in the following breeding season. Females fed diets as low as 7.5 MJ/kg ME in the previous breeding season produced significantly fewer eggs in the next breeding season, which resulted in lower chick production. Energy had no effect on the percentage infertile eggs or on the initial egg weight. Different levels of dietary protein had no effect on egg production, egg weight, fertility, hatchability and initial chick weight.
- Full Text:
- Date Issued: 2002
Analyzing communication flow and process placement in Linda programs on transputers
- De-Heer-Menlah, Frederick Kofi
- Authors: De-Heer-Menlah, Frederick Kofi
- Date: 1992 , 2012-11-28
- Subjects: LINDA (Computer system) , Transputers , Parallel programming (Computer science)
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4675 , http://hdl.handle.net/10962/d1006698 , LINDA (Computer system) , Transputers , Parallel programming (Computer science)
- Description: With the evolution of parallel and distributed systems, users from diverse disciplines have looked to these systems as a solution to their ever increasing needs for computer processing resources. Because parallel processing systems currently require a high level of expertise to program, many researchers are investing effort into developing programming approaches which hide some of the difficulties of parallel programming from users. Linda, is one such parallel paradigm, which is intuitive to use, and which provides a high level decoupling between distributable components of parallel programs. In Linda, efficiency becomes a concern of the implementation rather than of the programmer. There is a substantial overhead in implementing Linda, an inherently shared memory model on a distributed system. This thesis describes the compile-time analysis of tuple space interactions which reduce the run-time matching costs, and permits the distributon of the tuple space data. A language independent module which partitions the tuple space data and suggests appropriate storage schemes for the partitions so as to optimise Linda operations is presented. The thesis also discusses hiding the network topology from the user by automatically allocating Linda processes and tuple space partitons to nodes in the network of transputers. This is done by introducing a fast placement algorithm developed for Linda. , KMBT_223
- Full Text:
- Date Issued: 1992
- Authors: De-Heer-Menlah, Frederick Kofi
- Date: 1992 , 2012-11-28
- Subjects: LINDA (Computer system) , Transputers , Parallel programming (Computer science)
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4675 , http://hdl.handle.net/10962/d1006698 , LINDA (Computer system) , Transputers , Parallel programming (Computer science)
- Description: With the evolution of parallel and distributed systems, users from diverse disciplines have looked to these systems as a solution to their ever increasing needs for computer processing resources. Because parallel processing systems currently require a high level of expertise to program, many researchers are investing effort into developing programming approaches which hide some of the difficulties of parallel programming from users. Linda, is one such parallel paradigm, which is intuitive to use, and which provides a high level decoupling between distributable components of parallel programs. In Linda, efficiency becomes a concern of the implementation rather than of the programmer. There is a substantial overhead in implementing Linda, an inherently shared memory model on a distributed system. This thesis describes the compile-time analysis of tuple space interactions which reduce the run-time matching costs, and permits the distributon of the tuple space data. A language independent module which partitions the tuple space data and suggests appropriate storage schemes for the partitions so as to optimise Linda operations is presented. The thesis also discusses hiding the network topology from the user by automatically allocating Linda processes and tuple space partitons to nodes in the network of transputers. This is done by introducing a fast placement algorithm developed for Linda. , KMBT_223
- Full Text:
- Date Issued: 1992
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