Year of Award

2017

Document Type

Thesis

Degree Type

Master of Science (MS)

Degree Name

Computer Science

Department or School/College

Computer Science

Committee Chair

Travis Wheeler

Commitee Members

Travis Wheeler, Oliver Serang, Steve Lodmell

Keywords

multiple sequence alignment, computational biology, transitive sequence alignment, protein isoforms, alternative reading frames

Subject Categories

Computer Sciences | Other Computer Sciences

Abstract

A fundamental problem in computational biology is the organization of many related sequences into a multiple sequence alignment (MSA) [2]. MSAs have a range of research applications, such as inferring phylogeny [22] and identifying regions of conserved sequence that indicate functional similarity [18]. In the case of protein isoforms, MSAs are valuable tools for transitively annotating post-translational modifications (PTMs) by enabling information transfer between known PTM sites and the sites that they align to [11].

For protein MSA tools, one challenging biological phenomenon is alternative splicing, wherein identical genomic sequence will differentially select from a subset of available coding regions (exons), depending on the biochemical environment [21]. Traditional methods struggle to align the islands of non-homologous sequence produced by alternative splicing, and frequently compensate for the penalties incurred from aligning non-identical characters by aligning small pieces of relatively similar sequence from alternative exons in a way that avoids extreme gap penalties but falsely indicates sequence homology.

Presented here is Mirage, a novel protein MSA tool capable of accurately aligning alternatively spliced proteins by first mapping proteins to the genomic sequence that encoded them and then aligning proteins to one another based on the relative positions of their coding DNA. This method of transitive alignment demonstrates an awareness of intron splice site locations and resolves the problems associated with alternative splicing in traditional MSA tools.

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© Copyright 2017 Alex Nord