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Introduction to Sequence Alignment

Jun 6, 2025

Overview

This lecture focuses on the major sequence alignment algorithms in bioinformaticsтАФFAST and BLASTтАФand their applications.

Pairwise and Multiple Sequence Alignment

  • Pairwise alignment compares two sequences to align them based on matches, mismatches, and gaps.
  • Multiple sequence alignment involves several sequences, aligning them sequentially by adding one sequence at a time.
  • Alignments can be of two types: global (full sequence alignment) and local (partial sequence alignment).

Global and Local Alignment

  • Global alignment: The best alignment between two entire sequences is done using the Needleman-Wunsch algorithm.
  • Local alignment: Alignment of parts of sequences, comparing smaller sequences with larger ones or databases, using the Smith-Waterman algorithm.
  • Local alignment is used in tools like BLAST.

History of Sequence Alignment Algorithms

  • 1970: Needleman-Wunsch (global alignment)
  • 1981: Smith-Waterman (local alignment)
  • 1988: FASTA algorithm (by Pearson and Lipman)
  • 1990: BLAST algorithm (improvement on FASTA)
  • 1995 and beyond: Various versions of BLAST (such as Megablast) were developed

FASTA and BLAST Algorithms

  • FASTA was the first fast sequence search algorithm that allowed quick comparison of query sequences in a database.
  • BLAST is a modified and faster version of FASTAтАФsimpler, more user-friendly, and statistically more robust.
  • Both algorithms focus on finding small, exact matching segments.
  • Three stages of the algorithm: identifying small exact matches, extending them, and then optimizing the best hits.

Key Terms & Definitions

  • Alignment тАФ Matching of two or more sequences (similarity/difference).
  • Global Alignment тАФ Alignment of entire sequences.
  • Local Alignment тАФ Alignment of parts of sequences.
  • FASTA тАФ The first fast sequence search algorithm.
  • BLAST тАФ Basic Local Alignment Search Tool; a faster and more effective search tool.
  • Algorithm тАФ A step-by-step method for solving problems.

Action Items / Next Steps

  • In the next class, engage in practical study of FASTA and BLAST algorithms.
  • Practice with tools related to sequence alignment.