TOP 100 BIOINFORMATICS PROBLEMS (PYTHON)
SECTION 1: DNA / RNA / PROTEIN BASICS (1–20)
(Foundation – MUST know)
1. Count A, T, G, C in a DNA sequence
2. Calculate GC content
3. Reverse a DNA sequence
4. Find reverse complement
5. Validate a DNA sequence (invalid characters)
6. Transcribe DNA → RNA
7. Translate RNA → protein
8. Find start (ATG) and stop codons
9. Split DNA into codons
10. Find all open reading frames (ORFs)
11. Find longest ORF
12. Calculate molecular weight of protein
13. Count amino acid frequency
14. Detect palindromic sequences
15. Find motif occurrences in DNA
16. Find overlapping motifs
17. Compare two sequences and count mismatches
18. Calculate % identity between sequences
19. Detect low-complexity regions
20. Randomly generate DNA sequences
SECTION 2: SEQUENCE ALIGNMENT & COMPARISON (21–35)
21. Hamming distance between sequences
22. Edit distance (Levenshtein)
23. Global alignment (Needleman–Wunsch – logic level)
24. Local alignment (Smith–Waterman – logic level)
25. Score alignment using substitution matrix
26. Detect insertions and deletions
27. Align multiple sequences (concept + code logic)
28. Find conserved regions
29. Identify gaps and gap lengths
30. Compare protein sequences
31. Translate alignment positions to genome positions
32. Calculate alignment coverage
33. Extract mismatched bases
34. Compare reference vs sample sequence
35. Detect frameshift mutations
SECTION 3: MUTATIONS & VARIANTS (36–55)
(VERY IMPORTANT for interviews)
36. Detect SNPs between sequences
37. Detect InDels
38. Classify mutation (silent / missense / nonsense)
39. Count mutations per gene
40. Filter variants by quality score
41. Filter variants by allele frequency
42. Parse VCF file
43. Extract INFO field from VCF
44. Count variants per chromosome
45. Identify heterozygous vs homozygous variants
46. Annotate variant position with gene
47. Compare variants between two samples
48. Find common vs unique variants
49. Prioritize rare variants
50. Detect transition vs transversion
51. Calculate mutation rate
52. Detect hotspot mutations
53. Remove low-confidence variants
54. Convert VCF to table
55. Summarize variant statistics
SECTION 4: FILE HANDLING (FASTA / FASTQ / GFF / BAM) (56–70)
56. Read FASTA file
57. Write FASTA file
58. Read FASTQ file
59. Calculate average quality score
60. Filter low-quality reads
61. Count reads in FASTQ
62. Parse GFF/GTF file
63. Extract gene coordinates
64. Map variants to genes
65. Handle large files efficiently
66. Read compressed files (.gz)
67. Merge multiple FASTA files
68. Extract subsequence by coordinates
69. Validate file formats
70. Convert between formats
SECTION 5: GENE EXPRESSION & RNA-SEQ (71–85)
71. Read expression matrix (CSV/TSV)
72. Normalize gene expression
73. Remove low-expressed genes
74. Calculate fold change
75. Identify differentially expressed genes
76. Compare tumor vs normal samples
77. Find top N expressed genes
78. Cluster samples (logic + implementation)
79. Compute correlation between samples
80. Handle missing expression values
81. Summarize expression per condition
82. Filter genes by threshold
83. Merge metadata with expression data
84. Plot expression trends (basic)
85. Prepare data for downstream analysis
SECTION 6: DATA STRUCTURES & ALGORITHMIC THINKING (86–95)
86. Use dictionary for fast lookup
87. Index genome using hash map
88. Sliding window on sequences
89. Frequency counting optimization
90. Handle large datasets efficiently
91. Remove duplicates from biological data
92. Sort genes by score
93. Group data by gene/sample
94. Memory-efficient file reading
95. Parallel thinking (conceptual)
SECTION 7: REAL-WORLD / INTERVIEW-LEVEL PROBLEMS (96–100)
96. Build a mini variant analysis pipeline
97. Process 1 million DNA sequences efficiently
98. End-to-end FASTQ → variants → summary
99. Debug incorrect biological results
100. Explain Python solution to a biologist/non-coder
101. ADDITIONAL 20 MUST-LEARN BIOINFORMATICS PROBLEMS (Python)
102. Advanced Sequence Analysis
103. Identify CpG islands in a DNA sequence using sliding window
104. Calculate k-mer frequency for given k (k=3,4,6)
105. Find longest repeated substring in a genome
106. Detect tandem repeats in DNA
107. Identify restriction enzyme cut sites
108. Find GC skew across a genome
109. Predict simple promoters using consensus motifs
110. Detect poly-A tail in RNA sequences
111.
112. Variant & Genomics Logic
113. Annotate variants with exon / intron / UTR region
114. Determine whether a variant causes frameshift or in-frame change
115. Identify compound heterozygous variants in a gene
116. Compare trio data (child–mother–father) to detect de novo mutations
117. Prioritize variants using multiple filters (AF, impact, quality)
118. Merge VCF files from multiple samples
119. Detect structural variant breakpoints (logic level)
120.
121. RNA-seq / Expression & Data Science
122. Perform TPM normalization from raw read counts
123. Detect batch effects in expression data
124. Identify housekeeping genes across samples
125. Compare expression across multiple conditions/time points
126. Build a mini RNA-seq analysis pipeline (logic + code)
127.