In this dissertation, we describe a new approach for gene finding that can utilize proteomics information in addition to DNA and RNA to identify new genes in prokaryote genomes. Proteomics processing pipelines require identification of small pieces of proteins called peptides. Peptide identification is a very error-prone process and we have developed a new algorithm for validating peptide identifications using a distance-based outlier detection method. We demonstrate that our method identifies more peptides than other popular methods using standard mixtures of known proteins. In addition, our algorithm provides a much more accurate estimate of the false discovery rate than other methods. Once peptides have been identified and validated, we use a second algorithm, proteogenomic mapping (PGM) to map these peptides to the genome to find the genetic signals that allow us to identify potential novel protein coding genes called expressed Protein Sequence Tags (ePSTs). We then collect and combine evidence for ePSTs we generated, and evaluate the likelihood that each ePST represents a true new protein coding gene using supervised machine learning techniques. We use machine learning approaches to evaluate the likelihood that the ePSTs represent new genes. Finally, we have developed new approaches to Bayesian learning that allow us to model the knowledge domain from sparse biological datasets. We have developed two new bootstrap approaches that utilize resampling to build networks with the most robust features that reoccur in many networks. These bootstrap methods yield improved prediction accuracy. We have also developed an unsupervised Bayesian network structure learning method that can be used when training data is not available or when labels may not be reliable.
| Identifer | oai:union.ndltd.org:MSSTATE/oai:scholarsjunction.msstate.edu:td-3638 |
| Date | 08 August 2009 |
| Creators | Wang, Nan |
| Publisher | Scholars Junction |
| Source Sets | Mississippi State University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Theses and Dissertations |
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