ffsshhttiikk Bioinformatics
What I Do
Bioinformatics applies computational methods to analyze biological data. I cover sequence alignment, genome assembly, variant calling, phylogenetics, transcriptomics, proteomics, and systems biology. I help process NGS data, analyze biological networks, and extract insights from large-scale biological datasets.
When to Use Me
- Analyzing DNA, RNA, and protein sequences
- Processing next-generation sequencing data
- Performing genome assembly and annotation
- Identifying genetic variants and mutations
- Building and analyzing phylogenetic trees
- Studying gene expression and pathways
- Developing machine learning models for biological data
Core Concepts
- Sequence Alignment: BLAST, pairwise, multiple sequence alignment
- Sequence Analysis: ORFs, motifs, domains, functional annotation
- Genome Assembly: De Bruijn graphs, overlap-layout-consensus
- Variant Calling: SNPs, indels, structural variants, annotation
- Transcriptomics: RNA-seq, differential expression, pathway analysis
- Phylogenetics: Tree building, substitution models, bootstrap
- Proteomics: Protein identification, PTM analysis, structure prediction
- Machine Learning: Classification, clustering, regression models
- Biological Networks: PPI networks, gene regulation, metabolic pathways
- Data Visualization: Heatmaps, volcano plots, genome browsers
Code Examples
import numpy as np
from typing import List, Dict, Tuple
from collections import Counter
class SequenceAlignment:
def __init__(self, seq1: str, seq2: str):
self.seq1 = seq1.upper()
self.seq2 = seq2.upper()
def needleman_wunsch(self, match: int = 2,
mismatch: int = -1,
gap: int = -2) -> Tuple[np.ndarray, np.ndarray, str]:
m, n = len(self.seq1), len(self.seq2)
score = np.zeros((m + 1, n + 1))
for i in range(m + 1):
score[i, 0] = i * gap
for j in range(n + 1):
score[0, j] = j * gap
for i in range(1, m + 1):
for j in range(1, n + 1):
match_score = match if self.seq1[i-1] == self.seq2[j-1] else mismatch
score[i, j] = max(
score[i-1, j-1] + match_score,
score[i-1, j] + gap,
score[i, j-1] + gap
)
align1, align2 = "", ""
i, j = m, n
while i > 0 and j > 0:
if self.seq1[i-1] == self.seq2[j-1]:
match = match
else:
match = mismatch
if score[i, j] == score[i-1, j-1] + match:
align1 = self.seq1[i-1] + align1
align2 = self.seq2[j-1] + align2
i -= 1
j -= 1
elif score[i, j] == score[i-1, j] + gap:
align1 = self.seq1[i-1] + align1
align2 = "-" + align2
i -= 1
else:
align1 = "-" + align1
align2 = self.seq2[j-1] + align2
j -= 1
return score, score[m, n], (align1, align2)
def smith_waterman(self, match: int = 2,
mismatch: int = -1,
gap: int = -2) -> Tuple[np.ndarray, Dict]:
m, n = len(self.seq1), len(self.seq2)
H = np.zeros((m + 1, n + 1))
for i in range(1, m + 1):
for j in range(1, n + 1):
match_score = match if self.seq1[i-1] == self.seq2[j-1] else mismatch
H[i, j] = max(0, H[i-1, j-1] + match_score,
H[i-1, j] + gap, H[i, j-1] + gap)
max_score = H.max()
return H, {'max_score': max_score}
def calculate_identity(self) -> float:
matches = sum(1 for a, b in zip(self.seq1, self.seq2) if a == b)
return matches / min(len(self.seq1), len(self.seq2)) * 100
class VariantAnalysis:
def __init__(self, vcf_file: str):
self.vcf_file = vcf_file
def annotate_variant(self, chromosome: str, position: int,
reference: str, alternate: str) -> Dict:
impact = "MODERATE"
consequence = "missense_variant"
if len(reference) == 1 and len(alternate) == 1:
consequence = "SNP"
elif len(reference) > len(alternate):
consequence = "deletion"
elif len(alternate) > len(reference):
consequence = "insertion"
if reference == "ATG" and alternate == "GTG":
consequence = "start_lost"
return {
'chromosome': chromosome,
'position': position,
'reference': reference,
'alternate': alternate,
'consequence': consequence,
'impact': impact
}
def calculate_zygosity(self, read_depth: int,
alt_reads: int) -> str:
alt_fraction = alt_reads / read_depth
if alt_fraction > 0.75:
return "homozygous_alt"
elif alt_fraction > 0.25:
return "heterozygous"
return "homozygous_ref"
def pathogenicity_prediction(self, variant: Dict) -> Dict:
score = 0
if variant['consequence'] == "stop_gained":
score += 0.8
elif variant['consequence'] == "missense_variant":
score += 0.3
return {
'pathogenicity_score': score,
'prediction': 'pathogenic' if score > 0.5 else 'benign'
}
class NGSAnalysis:
def __init__(self, sample: str):
self.sample = sample
def calculate_coverage(self, aligned_reads: int,
genome_size: float) -> float:
return aligned_reads * 150 / (genome_size * 1e6)
def expression_analysis(self, counts: Dict[str, float],
library_size: float) -> Dict:
tpm = {}
for gene, count in counts.items():
length = 1000 # Average gene length
tpm[gene] = (count / length) / (sum(c/l for c,l in [(c,1000) for c in counts.values()])) * 1e6
return tpm
def differential_expression(self, control_tpm: Dict,
treated_tpm: Dict,
threshold: float = 2) -> List[Dict]:
de_genes = []
for gene in control_tpm:
if gene in treated_tpm:
fc = treated_tpm[gene] / (control_tpm[gene] + 0.1)
if abs(np.log2(fc)) > np.log2(threshold):
de_genes.append({
'gene': gene,
'fold_change': fc,
'log2_fc': np.log2(fc)
})
return de_genes
class SequenceAnalysis:
def __init__(self, sequence: str):
self.sequence = sequence.upper()
def calculate_gc_content(self) -> float:
gc = sum(1 for base in self.sequence if base in 'GC')
return gc / len(self.sequence) * 100
def find_orfs(self, min_length: int = 100) -> List[Dict]:
codons = []
for frame in range(3):
for i in range(frame, len(self.sequence) - 2, 3):
codon = self.sequence[i:i+3]
if codon == 'ATG':
for j in range(i, len(self.sequence) - 2, 3):
if self.sequence[j:j+3] in ['TAA', 'TAG', 'TGA']:
orf_len = j + 3 - i
if orf_len >= min_length:
codons.append({
'start': i,
'end': j + 3,
'length': orf_len,
'frame': frame
})
break
return codons
seq1 = "ATCGATCGATCG"
seq2 = "ATCGTTCGATCG"
aligner = SequenceAlignment(seq1, seq2)
score, max_score, alignment = aligner.needleman_wunsch()
print(f"Alignment score: {max_score}")
print(f"Alignment: {alignment[0]}\n {alignment[1]}")
print(f"Identity: {aligner.calculate_identity():.1f}%")
gc = aligner.calculate_gc_content()
print(f"GC Content: {gc:.1f}%")
Best Practices
- Use appropriate reference genomes and annotations
- Apply proper quality control to sequencing data
- Use appropriate statistical methods for differential analysis
- Validate computational predictions experimentally
- Document pipeline parameters for reproducibility
- Use appropriate multiple testing corrections
- Consider batch effects in large datasets
- Use standardized data formats (FASTA, FASTQ, BAM, VCF)
- Report confidence intervals for estimates
- Share code and data when possible for reproducibility