Overcoming missing data in phylogenetic analysis of shotgun sequencing to detect HIV adaptation to immune response
department or school: Science, Faculty of
data provider: DSpace
degree campus: UBCV
creator: Nguyen, Thuy
issued: 2016-09-08T02:02:33
issued: 2016
related degree: Master of Science - MSc
degree grantor: University of British Columbia
description: DNA sequencing gives us insight into how viruses adapt to their host immune systems. Studies of viral populations typically employ deep amplicon sequencing with next-generation reads to capture a detailed sample of genetic variation in a population. The high amount of overlapping sites in a multiple sequence alignment of reads from amplicon sequencing form ideal input for phylogenetic reconstruction, a necessary step for studying evolutionary relations in a population. However, the typical short read lengths of < 600 bp from next generation sequencing technology with the best sequence error rate impose a severe limit on the width of genomic regions for which evolutionary relationships can be analyzed. Shotgun sequencing, in which DNA is fragmented at random positions, is an efficient alternative to amplicon sequencing for covering wider regions of a genome with sufficient depth. Due to the random staggered positions of shotgun reads in a genome, an extremely high percentage of missing data can result in multiple sequence alignment of shotgun sequencing. The absence of sequence homology across the entire set of short reads makes it impossible to reconstruct a phylogenetic tree, limiting the utility of shotgun data for phylogenetic analysis. We developed the Umberjack software pipeline, which employs a 'sliding window' approach to minimize the effect of missing data during phylogenetic reconstruction and obtain evolutionary statistics to detect sites under selection. Using Umberjack to measure a new metric of directional selection I, significant directional selection was detected in treatment-naive HIV populations at sites with previously documented associations with cytotoxic T-lymphocyte (CTL) response. Further, substitutions towards wild-type amino acids were found to occur early within the population's history, but rarely occurred at a site after the appearance of a CTL escape mutation. Measuring the same metric I in drug treated HIV populations, the directional s…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/59108
note: Overcoming Missing Data in Phylogenetic Analysis ofShotgun Sequencing to Detect HIV Adaptation to ImmuneResponsebyThuy NguyenA THESIS SUBMITTED IN PARTIAL FULFILLMENTOF THE REQUIREMENTS FOR THE DEGREE OFMaster of ScienceinTHE FACULTY OF GRADUATE AND POSTDOCTORALSTUDIES(Bioinformatics)The University of British Columbia(Vancouver)August 2016c© Thuy Nguyen, 2016AbstractDNA sequencing gives us insight into how viruses adapt to their host immune sys-tems. Studies of viral populations typically employ deep amplicon sequencing withnext-generation reads to capture a detailed sample of genetic variation in a popu-lation. The high amount of overlapping sites in a multiple sequence alignment ofreads from amplicon sequencing form ideal input for phylogenetic reconstruction,a necessary step for studying evolutionary relations in a population. However, thetypical short read lengths of <600 bp from next generation sequencing technologywith the best sequence error rate impose a severe limit on the width of genomicregions for which evolutionary relationships can be analyzed.Shotgun sequencing, in which DNA is fragmented at random positions, is anefficient alternative to amplicon sequencing for covering wider regions of a genomewith sufficient depth. Due to the random staggered positions of shotgun reads ina genome, an extremely high percentage of missing data can result in multiplesequence alignment of shotgun sequencing. The absence of sequence homologyacross the entire set of short reads makes it impossible to reconstruct a phylogenetictree, limiting the utility of shotgun data for phylogenetic analysis.We developed the Umberjack software pipeline, which employs the ‘slidingwindow’ approach to minimize the effect of missing data during phylogenetic re-construction and obtain evolutionary statistics to detect sites under selection.Using Umberjack to measure a new metric of directional selection I, signifi-cant directional selection was detected in treatment-naive HIV populations at…
has type: Thesis/Dissertation
date issued: 2016-02
is shown at: 10.14288/1.0314165
language: eng
degree discipline: Bioinformatics
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc/4.0/
scholar level: Graduate
type: Text
identifier URI: http://hdl.handle.net/2429/59108