Structural Variation in the Caenorhabditis elegans Genome: Challenges and Quality Assurance Strategies for Reliable Variant Calling
Date
2023-08
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Abstract
Obtaining an accurate and comprehensive representation of structural variation is crucial for understanding how large alterations in chromosome structure contribute to phenotype diversity and drive genome evolution. Despite continuous efforts into improving methods for identifying structural variation from whole genome sequencing data, accurate variant calling remains challenging. The barriers to progress in this area are complex and multifactorial but the technical limitations of short-read sequencing technologies and limited availability of suitable benchmarking resources for non-human species feature prominently. This thesis includes an in-depth evaluation of several commonly used tools for identifying structural variants from short- and long-read DNA sequencing data from natural Caenorhabditis elegans strains. The results of these comparisons revealed that popular tools yield considerably different results, which are described in detail in Chapter 2. A major aim of this project was to identify sources of error and variability that tool developers could address in the future. Surprisingly, the order of reads in PacBio FASTQ files were revealed to affect the predicted structural variants. Chapter 3 describes these results and demonstrates how alignment sorting algorithms contribute to the problem. In Chapter 4, an analysis of structural variation in 14 natural C. elegans strains is described. Importantly, this work demonstrates how long-read DNA sequencing data can be successfully used to identify structural variants at the population level.
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Keywords
structural variation, Caenorhabditis elegans, genomics, bioinformatics
Citation
Lesack, K. J. (2023). Structural variation in the Caenorhabditis elegans genome: challenges and quality assurance strategies for reliable variant calling (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.