Long, QuanMak, Lauren2019-07-152019-07-152019-07-10Mak, L. (2019). Resolving Complex Microbial Populations and Transmission Networks Through Haplotype Reconstruction (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.http://hdl.handle.net/1880/110639Next-generation sequencing (NGS) is frequently applied to a mixture of genomes from a complex population that has to be bulk-sequenced. For instance, in virology, the outcome of viral sequencing is generally a mixture of different viruses called ‘quasispecies’. For downstream analyses such as within-host evolution, the quasispecies need to be reconstructed by de-convoluting the aggregated variation data in silico. In this project, I have contributed to the fields of within- and between-host evolutionary analysis by 1) designing and implementing a state-of-the-art haplotype reconstruction program, PoolHapX and 2) quantifying the accuracy of transmission relationship inference from patient pathogen consensus sequences. Existing haplotype reconstruction tools usually use either read-based genomics information or statistics-based linkage sharing across population(s). PoolHapX is the first haplotype reconstruction tool to integrate read-based genomics information and statistics-based linkage-sharing across the population to handle very long sequences, opening new avenues for study into complex within-host populations. I have additionally demonstrated that with consensus sequences alone, a maximum of 67% of person-to-person transmission relationships can be accurately recovered. In the future, within-host haplotypes will be integrated into transmission inference methods to improve inference accuracy. Improvements in the resolution of within- and between-host linkage patterns will empower local epidemiological control; for example, by identifying the genetic properties of high-risk transmission groups to target for clinical support.engUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.HaplotypeHIVTransmissionAlgorithmMicrobialReconstructionBiologyBioinformaticsBiostatisticsVirologyBiophysics--MedicalEpidemiologyMathematicsStatisticsComputer Sciencemaster thesis10.11575/PRISM/36746