TZMD

TZMD computes Manhattan Distance on z-value–normalized tetranucleotide frequencies to quantify genomic composition differences and enable high-resolution discrimination of closely related bacterial genomes, including strains, species, subspecies, and genospecies.

Key Features:

• Tetranucleotide z-value normalization: Uses z-value normalization of tetranucleotide frequency patterns to standardize compositional signals across genomes.
• Z-value Manhattan Distance (TZMD): Calculates Manhattan Distance on z-values to measure genomic composition dissimilarity between genomes.
• Comparison to TETRA: Assessed against the Tetranucleotide-derived Z-value Pearson correlation coefficient (TETRA) and reported to reflect maximal genome differences more accurately.
• High-resolution discrimination: Resolves differences among bacterial species, subspecies, genospecies, and intraspecific strains at finer scale than conventional composition-based approaches.
• Clonal strain criterion (TZMD = 0): Defines clonal or compositionally identical strains by a TZMD value of zero, which corresponds to identical genomic composition, high average nucleotide identity (ANI), and a large percentage of shared genomes.

Scientific Applications:

• Strain typing: Enables composition-based strain-level typing and discrimination of closely related bacterial isolates.
• Clonal strain identification: Identifies clonal or compositionally identical strains using the TZMD = 0 criterion.
• Taxonomic resolution: Distinguishes bacterial species, subspecies, and genospecies that may be indistinguishable by TETRA.
• Genomic composition analysis: Quantifies genome-wide compositional differences for studies of microbial diversity and evolution.

Methodology:

Compute tetranucleotide frequencies, convert frequencies to z-values, calculate Manhattan Distance between genomes (TZMD), compare results to TETRA (tetranucleotide-derived z-value Pearson correlation coefficient), and designate TZMD = 0 as indicative of clonal/compositionally identical genomes.