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- PostA Pipeline for Comparison of Clustering Methods in Flow Cytometry Analysis(2013) Farahbod, Marjan; Chalmers tekniska högskola / Institutionen för matematiska vetenskaper; Chalmers University of Technology / Department of Mathematical Sciences
- PostBenchmarking of read mapping bias in allele specific expression analysis(2013) James, Alva Rani; Chalmers tekniska högskola / Institutionen för matematiska vetenskaper; Chalmers University of Technology / Department of Mathematical SciencesMost genes in diploid organisms have two “copies”; one copy inherited from each parent. If an individual has two different alleles (code variants) at a specific gene locus, then the individual is heterozygous at that locus. Allele specific expression (ASE) can be explained as the differential expression between the two different alleles of a gene in a single individual. There are several mechanisms that can cause ASE, e. g, it can be caused by a heterozygous variant in the promoter region, causing a difference in transcription factor binding affinity between the maternal and paternal allele. Accurate measurement and identification of ASE can be obtained by precise mapping of reads, generated from RNA next generation sequencing (RNA-seq), towards the reference genome of the organism. Mapping bias is a major technical hurdle in ASE studies which arises when we map short RNA-seq reads towards a reference genome. This arises mainly when the reads which carries non-reference alleles is not matching towards the reference genome gives out a lower mapping quality. In this thesis we investigated two proposed methods to reduce mapping bias: a read mapping program called GSNAP, and masking the reference genome with respect to single nucleotide variants. Masking the reference genome removed the mapping bias to a greater degree than GSNAP; however, the masking caused a considerable drop in read coverage. In conclusion, none of the two methods reduced the mapping bias satisfactorily, highlighting the importance to develop new or modified methods for mapping bias reduction.
- PostBioinformatics and Statistical Methods for Identifying Enrichment of Functional Gene Classes in Telomeric Regions of Chromosomes(2013) Ahamed, Tanvir Mohammad; Chalmers tekniska högskola / Institutionen för matematiska vetenskaper; Chalmers University of Technology / Department of Mathematical SciencesIt has been noted that the telomeric regions of Saccharomyces cerevisiae has fewer essential genes than expected from random shuffling. Further the general effect of single gene silencing of non-essential genes in the telomeric regions with an average has less effect on viability than for non-essential genes in other chromosomal regions. It has also been suggested that the genes in the telomeric regions are less stable with higher mutation and recombination rates. And this could be an evolutionary positive property for adaption of genes with changing environment, provided that there are back up systems for the genes. In this work, we took a look at some different statistical properties of the telomeres and the genes in the telomeric regions. Some of the studied properties are: How dense the code is in the telomeric region compared to the rest of the genome? What length distribution do the genes have in the telomeric region in comparison to the general length distribution? What GO-annotated classes are over-represented in telomeres? Can we find protein sequence clusters that are over-represented in the telomeres? We have found fairly a lot of interesting properties and at least partly our results also support the earlier suggestions. Finally, for the future, we suggest that comparison of our different finding corresponding telomeric statistical properties in Saccharomyces cerevisiae should be performed with other yeast species, like Schizosaccharomyces pombe, which is evolutionary distant enough to be genomically fairly reshuffled. As usual, in multivariate statistics, the statistical properties are correlated (Length correlates to viability, function, etc.) and causality is hard to deduce, but may be easier to understand using more organisms. The main findings of the thesis were that, there is less code in the extreme telomeric region. In percentage, long essential genes in the telomeric region are very few. The numbers of genes in the long non-essential gene category are larger but also quite few compared to elsewhere. And of those that reside in the telomeric region, there are many genes related to metal ion transport, disaccharide and oligosaccharide metabolic and catabolic process. The pipeline of methods used in the present research also identifies some gene function related to helicase activity that has been pointed out in earlier research.
- PostHomology Modelling of Norovirus GII.3 Surface Domains A comparative analysis with focus on the evolving norovirus sequence in a chronic infection(2012) Nordgren, Niklas; Chalmers tekniska högskola / Institutionen för data- och informationsteknik (Chalmers); Chalmers University of Technology / Department of Computer Science and Engineering (Chalmers)
- PostP27 deficiency accelerates the development of PTEN-deficiency-induced myeloproliferative disease(2015) Shao, Jingchen; Chalmers tekniska högskola / Institutionen för biologi och bioteknik; Chalmers University of Technology / Department of Biology and Biological EngineeringPTEN acts as a phosphatase for PIP3 and negatively regulates the PI3K/AKT pathway, and CDKN1B (P27KIP1) is a cyclin-dependent kinase inhibitor that regulates G0 to S phase transitions by binding to and regulating the activity of cyclin-dependent kinases. Genetic alternations of Pten or Cdkn1b are common in hematological malignancies. Combined loss of PTEN and P27KIP1 expression is associated with tumor cell proliferation and poor prognosis in prostate cancer. However, it is not so clear how two mutations would cooperate in leukemogenesis. Here, we show that combined inactivation of PTEN or P27KIP1 in the hematopoietic compartment in mice results in a more severe myeloproliferative disease phenotype with shorter lifespan, lower hemoglobin and more enlarged spleen, lever comparted inaction of Pten or p27KIP1 alone.
- PostStudy of the evolution of repeat domains in autotransporter proteins(2013) Panneerseljam, Senthil Kumar; Chalmers tekniska högskola / Institutionen för kemi- och bioteknik; Chalmers University of Technology / Department of Chemical and Biological Engineering