Loading icon

Implement a Simplified BLAST-Like Sequence Search Algorithm in Python

Post banner image
Share:

Creating a BLAST-like algorithm from scratch is a complex task, and typically requires a good understanding of bioinformatics, algorithm design, and programming. However, I'll provide an outline of how you might approach this task using built-in Python functions and numpy for the matrix manipulations necessary in the alignment processes. Below is a simplified example of how you might implement a local sequence alignment algorithm (similar to BLAST) to perform sequence searches.

Applications:


1. Sequence Alignment and Identification: Identify and align sequences to study similarities and differences, crucial for comparative genomics and evolutionary studies.

2. Primer Design: Search for specific sequences to design primers for PCR (Polymerase Chain Reaction).

3. Functional Annotation: Annotate unknown sequences based on similarity to known sequences.

Algorithm Outline:

1. Database Indexing: Index the database sequences to enable fast searching.

2. Seed Identification: Identify exact or near-exact matches (seeds) between the query sequence and database sequences.

3. Extension: Extend the seeds to high-scoring pairs (HSPs) by aligning the sequences using dynamic programming.

4. Scoring and Reporting: Score the alignments and report the results.

Example:



    import numpy as np

    def create_index(database):
        # Simple indexing based on k-mers
        index = {}
        k = 3  # length of k-mers
        for i, sequence in enumerate(database):
            for j in range(len(sequence) - k + 1):
                kmer = sequence[j:j+k]
                if kmer not in index:
                    index[kmer] = []
                index[kmer].append((i, j))
        return index
    
    def local_alignment(seq1, seq2):
        # Smith-Waterman algorithm for local alignment
        m, n = len(seq1), len(seq2)
        score_matrix = np.zeros((m+1, n+1))
        for i in range(1, m+1):
            for j in range(1, n+1):
                match = score_matrix[i-1, j-1] + (1 if seq1[i-1] == seq2[j-1] else -1)
                delete = score_matrix[i-1, j] - 1
                insert = score_matrix[i, j-1] - 1
                score_matrix[i, j] = max(0, match, delete, insert)
        return score_matrix

This example demonstrates a simplified approach to sequence searching. The create_index function builds a simple index based on k-mers from the database sequences. The local_alignment function performs local sequence alignment using a simplified Smith-Waterman algorithm.

    
    def traceback(score_matrix, seq1, seq2, i, j):
        # Function to perform traceback and extract alignment
        alignment1, alignment2 = '', ''
        while i > 0 and j > 0:
            score_current = score_matrix[i, j]
            score_diagonal = score_matrix[i-1, j-1]
            score_up = score_matrix[i, j-1]
            score_left = score_matrix[i-1, j]
            if score_current == 0:
                break
            elif score_current == score_diagonal + (1 if seq1[i-1] == seq2[j-1] else -1):
                alignment1 += seq1[i-1]
                alignment2 += seq2[j-1]
                i -= 1
                j -= 1
            elif score_current == score_up - 1:
                alignment1 += '-'
                alignment2 += seq2[j-1]
                j -= 1
            else:  # score_current == score_left - 1
                alignment1 += seq1[i-1]
                alignment2 += '-'
                i -= 1
        return alignment1[::-1], alignment2[::-1]
    
    def search(query, database):
        index = create_index(database)
        k = 3  # length of k-mers
        results = []  # List to store the results
        for i in range(len(query) - k + 1):
            kmer = query[i:i+k]
            if kmer in index:
                for seq_id, position in index[kmer]:
                    db_seq = database[seq_id]
                    # Perform local alignment around the seed match
                    start = max(0, position - 10)
                    end = min(len(db_seq), position + k + 10)
                    score_matrix = local_alignment(query, db_seq[start:end])
                    # Extract and report high-scoring pairs (HSPs) from the score matrix
                    max_score = np.max(score_matrix)
                    if max_score > 0:
                        max_position = np.unravel_index(np.argmax(score_matrix), score_matrix.shape)
                        alignment1, alignment2 = traceback(score_matrix, query, db_seq[start:end], *max_position)
                        results.append({
                            'score': max_score,
                            'query_alignment': alignment1,
                            'db_alignment': alignment2,
                            'db_sequence_id': seq_id,
                            'position': (start + max_position[1] - len(alignment2), start + max_position[1])
                        })
        return results  # Return the results
    
    # Example usage:
    database = ["ATGCGCATCGA", "GCTAGCTAGCTA", "CGTAGCTAGCTAG"]
    query = "GCGCAT"
    results = search(query, database)
    for result in results:
        print(f"Score: {result['score']}\nQuery Alignment: {result['query_alignment']}\nDatabase Alignment: {result['db_alignment']}\nDatabase Sequence ID: {result['db_sequence_id']}\nPosition: {result['position']}\n")
    
    
    

Traceback function is defined to extract the alignments from the score matrix, starting from the position of the highest score and working backwards to the origin (or until a score of 0 is encountered). The search function is updated to call this traceback function to obtain the alignments for each high-scoring pair (HSP), and these are stored in a results list which is returned at the end. Each result is a dictionary containing the score, alignments, database sequence ID, and positions of the alignment in the database sequence.

Happy Coding!!