Pairwise sequence alignment in bioinformatics

Pairwise Sequence Alignment in Bioinformatics

Pairwise sequence alignment is a fundamental technique in bioinformatics that involves comparing two biological sequences (DNA, RNA, or protein) to identify regions of similarity. These similarities can provide insights into evolutionary relationships, functional similarities, and structural predictions.

Key Concepts

 * Similarity: The degree to which two sequences are alike.

 * Identity: The percentage of identical characters (nucleotides or amino acids) at corresponding positions.

 * Similarity: The percentage of characters that are either identical or have similar biochemical properties.

 * Homology: The evolutionary relationship between two sequences, suggesting a common ancestor.

Types of Alignment

 * Global Alignment: Aligns the entire length of two sequences, often used for sequences of similar length and expected to be similar throughout.

   * Needleman-Wunsch Algorithm: A dynamic programming algorithm for optimal global alignment.

 * Local Alignment: Identifies regions of similarity within longer sequences, useful for finding conserved domains or motifs.

   * Smith-Waterman Algorithm: A dynamic programming algorithm for optimal local alignment.

Scoring Matrices

 * Substitution Matrices: Assign scores to matches, mismatches, and gaps based on the likelihood of certain substitutions occurring during evolution.

   * PAM (Point Accepted Mutation) matrices: Based on observed amino acid changes in closely related proteins.

   * BLOSUM (Blocks Substitution Matrix) matrices: Derived from multiple alignments of protein families, often considered more accurate than PAM matrices.

Gap Penalties

 * Gap Opening Penalty: A penalty for introducing a gap in a sequence.

 * Gap Extension Penalty: A penalty for extending an existing gap.

Applications

 * Identifying Homologous Sequences: Determining evolutionary relationships and inferring protein function.

 * Protein Structure Prediction: Predicting the three-dimensional structure of a protein based on its sequence similarity to proteins with known structures.

 * Primer Design: Designing primers for PCR (Polymerase Chain Reaction) experiments.

 * Genome Annotation: Identifying genes and other functional elements within a genome.

Tools

 * BLAST (Basic Local Alignment Search Tool): A widely used tool for performing local alignments against large databases.

 * ClustalW: A popular tool for multiple sequence alignment, which can also be used for pairwise alignment.

 * Needle: A tool for performing global alignments using the Needleman-Wunsch algorithm.

Visualizing Alignments

 * Dot Plots: Graphical representations of sequence similarity, showing diagonal lines for regions of similarity.

 * Sequence Alignment Viewers: Specialized software for visualizing alignments, often with color-coding to highlight conserved regions.

By understanding the principles of pairwise sequence alignment, researchers can gain valuable insights into the relationships between biological sequences and their functional and evolutionary implications.