OPTIMAL SEQUENCE ALIGNMENTS Given any two sequences, there are an enormous number of ways they can be aligned if one allows for insertions and deletions (collectively referred to as indels or gaps) in the alignment. This chapter introduction provides a primer on five fundamental issues related to similarity searches: (1) how to find the best alignment between two sequences (2) methods for scoring an alignment (3) speeding up database searches (4) determining statistical significance and (5) using information in multiple alignments to improve sensitivity. The units in this Chapter all address aspects of this problem, finding significant similarity between new sequences and those that are currently in the databases of known sequences. The methods for identifying homologous sequences rely on finding similarities between sequences that are unlikely to happen by chance, thereby allowing the inference that the sequences have evolved from a common ancestor. Because homologous sequences, those related by common ancestry, generally have the same or very similar functions, their identification can be used to infer the function of the new sequence. Keywords: sequence similarity r homology r dynamic programming r similarity-scoring matrices r sequence alignment r multiple alignment r sequence evolutionĪN INTRODUCTION TO IDENTIFYING HOMOLOGOUS SEQUENCES Upon determining a new sequence, one common objective is to assign a function to that sequence, or perhaps multiple functions to various subsequences. This unit provides an overview of some of the basic issues in identifying similarity among sequences and points out other units in this chapter that describe specific C 2009 programs that are useful for this task. Homology is inferred based on sequence similarity, and many methods have been developed to identify sequences that have statistically significant similarity. Louis, MissouriĪBSTRACT Homologous sequences usually have the same, or very similar, functions, so new sequences can be reliably assigned functions if homologous sequences with known functions can be identified. Washington University, School of Medicine, St. An Introduction to Sequence Similarity (“Homology”) Searching
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