Implement a Simplified BLAST-Like Sequence Search Algorithm in Python
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!!