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Data Dictionary

Input Data

All input data is downloaded automatically by the scripts at runtime. Nothing needs to be uploaded manually.

Genome & Annotation Files (cached to data/ at runtime)

File Source Size
data/yeast_genome.fsa Ensembl R64-1-1 (release 110) 12.16 Mb
data/yeast.gff3.gz Ensembl release 110

Genome assembly: S. cerevisiae S288C, R64-1-1, 12,157,105 bp across 17 chromosomes including mitochondria.


Output Data

All output files are written to results/ by running the scripts in order.

Nullomer List

results/nullomers_k11.txt — generated by scripts/01_nullomer_identification.py

  • One 11-mer sequence per line, sorted alphabetically
  • 463,220 sequences (11.04% of the 4,194,304 theoretical 11-mers)
  • Mean GC content: 65.7% (vs 38.3% genome-wide)
  • Both forward and reverse-complement strands are accounted for

NEM Analysis

results/nem_comprehensive_summary.csv — generated by scripts/02_nem_analysis.py

Column Type Description
gene string Gene name (e.g. PDR5)
region string gene, promoter, or downstream
nem_count integer Number of nullomer-emerging mutations
seq_length integer Length of the region in bp
nem_density_per_kb float NEMs per kilobase
type string Functional classification
essential boolean Gene essentiality
stress boolean Stress-responsive classification
subfamily string ABC transporter subfamily

78 rows (26 genes × 3 regions). Total NEMs across all regions: 174,799.

results/nem_enrichment_analysis.csv — generated by scripts/02_nem_analysis.py

Column Type Description
gene string Gene name
region string gene, promoter, or downstream
observed_nems integer Observed NEM count
expected_nems float Expected under Poisson null
enrichment_ratio float Observed / expected
p_value float Poisson p-value
p_adjusted float Bonferroni-corrected p-value
significant boolean p_adjusted < 0.05

results/stress_permutation_test.json — generated by scripts/02_nem_analysis.py

Permutation test results (10,000 iterations) comparing NEM density between stress-responsive and non-stress genes. Fields: stress_mean, stress_std, nonstress_mean, nonstress_std, observed_diff_nems_per_kb, mannwhitney_u, mannwhitney_p, permutation_p, cohens_d, n_stress, n_nonstress.


Stress Element Analysis

results/stress_element_nem_correlation.csv — generated by scripts/03_stress_element_analysis.py

Column Type Description
gene string Gene name
promoter_length integer Promoter length in bp (1000 bp)
promoter_nems integer NEM count in promoter
nem_density_per_kb float Promoter NEM density
total_stress_elements integer Sum of all binding sites
PDRE integer Pleiotropic Drug Response Element count
STRE integer Stress Response Element count
HSE integer Heat Shock Element count
AP1 integer AP-1 element count
type string Functional classification
essential boolean Gene essentiality
stress boolean Stress-responsive classification
is_drug_efflux boolean Drug efflux gene flag

26 rows (one per gene). Key result: PDRE count correlates with NEM density at Spearman ρ=0.685, p=1.1×10⁻⁴.

results/motif_disruption_by_nems.csv — generated by scripts/03_stress_element_analysis.py

Column Type Description
gene string Gene name
nem_position integer Position in promoter sequence
nem_mutation string Mutation notation (e.g. A142G)
element_type string PDRE, STRE, HSE, or AP1
motif_position integer Motif start position
motif_strand string + or -
position_in_motif integer Position of NEM within the motif

Records where a single mutation both creates a nullomer and falls inside a known TF binding site. Total: 16,480 disruptions across all elements.


Thermodynamic Analysis

results/nullomer_thermodynamics.csv — generated by scripts/04_thermodynamic_analysis.py

Column Type Description
sequence string 11-mer sequence
group string nullomer or random
Tm float Melting temperature (°C)
dG float Gibbs free energy at 37°C (kcal/mol)
GC float GC fraction (0–1)
hairpin boolean Palindromic hairpin potential
g4 boolean G-quadruplex motif (GGGG) present
imotif boolean i-motif motif (CCCC) present

20,000 rows (10,000 nullomers + 10,000 random controls). Parameters: SantaLucia (1998) nearest-neighbour, 37°C, 1 M NaCl.

results/thermodynamic_summary.json — generated by scripts/04_thermodynamic_analysis.py

Key values confirmed against the manuscript:

Metric Nullomers Random
Mean Tm 41.73 ± 5.70 °C 35.56 ± 6.63 °C
Mean ΔG −13.96 ± 1.52 kcal/mol −12.13 ± 1.80 kcal/mol
ΔΔG 1.83 kcal/mol
Boltzmann fold disadvantage 19.4×
GC–Tm Pearson r 0.803
Very stable (ΔG < −10) 99.7%
Hairpin potential 22.4%
G-quadruplex 1.0%
i-motif 1.2%

ML and Network Analysis

results/ml_feature_importance.csv — generated by scripts/05_ml_and_network_analysis.py

Column Type Description
feature string Feature name
importance float Random Forest mean decrease in impurity

Top features: at_content (0.359), gc_content (0.356), cg_dinuc (0.153).

results/ml_model_performance.json — generated by scripts/05_ml_and_network_analysis.py

Random Forest performance (100 bp windows, 50 bp step, 26 genes):

Metric Value
Test R² 0.760
Test RMSE 41.46 NEMs
CV R² (5-fold) 0.717 ± 0.045

Also contains Gaussian Process fitness landscape results: R²=0.896, RMSE=93.8 NEMs/kb.

results/network_topology.csv — generated by scripts/05_ml_and_network_analysis.py

Column Type Description
gene string Gene name
nem_density float NEM density (NEMs/kb)
degree integer Number of STRING interaction partners
betweenness float Betweenness centrality
closeness float Closeness centrality
eigenvector float Eigenvector centrality
is_drug_efflux boolean Drug efflux gene flag

Network: 26 nodes, 13 edges (STRING v11.5, score ≥ 400, physical interactions only).

results/fragility_scores.csv — generated by scripts/05_ml_and_network_analysis.py

Column Type Description
gene string Gene name
fragility_score float F = 0.4×(NEM/5000) + 0.3×(degree/n) + 0.3×(neighbor_NEM/5000)

Top 5: PDR15 (1.402), PDR10 (1.330), PDR5 (1.238), SNQ2 (1.161), PDR12 (1.076).


Statistical Synthesis

results/statistical_synthesis.json — generated by scripts/06_statistical_synthesis.py

Contains all four hypothesis tests and Fisher's combined p-value:

Test Result
H1: Stress vs non-stress NEM density Mann-Whitney p=0.019, permutation p=0.006, d=1.36
H2: PDRE–NEM correlation Spearman ρ=0.685, p=1.1×10⁻⁴, slope=85.5 NEMs/kb per PDRE
H3: Drug efflux vs other Mann-Whitney p=0.018, Cohen's d=1.08
H4: Promoter vs gene body density Wilcoxon p=0.003, enrichment=22.6%
Meta-analysis (Fisher) χ²=51.32, df=8, combined p=2.28×10⁻⁸

ABC Transporters Analyzed

26 genes spanning: drug efflux pumps (PDR5, SNQ2, YOR1, PDR10, PDR11, PDR12, PDR15, PDR18, YCF1), transcriptional regulators of drug resistance (PDR1, PDR3, PDR16, PDR17), mitochondrial transporters (ATM1, MDL1, MDL2), translation-related (YEF3, GCN20, ARB1, RLI1), and others (VMR1, YBT1, BPT1, HMT1, NMD5, STE6).

Promoter length used throughout: 1000 bp upstream of each start codon.


File Formats

All CSV files use comma separation, UTF-8 encoding, and a header row. JSON files use UTF-8 with two-space indentation. The nullomer list (nullomers_k11.txt) has one 11-mer per line, sorted lexicographically.