NUQA

NUQA performs alignment-free comparison of raw fastq sequencing data to quantify spatial and temporal heterogeneity in cancer samples and infer evolutionary relationships.

Key Features:

• Alignment-Free Sequence Comparison: Compares sequencing data without alignment to avoid information loss from complex tumor mutational landscapes.
• K-mer Counting: Utilizes k-mer counting methods to represent raw fastq sequencing content for sample comparison.
• Distance Metrics: Computes Jensen-Shannon divergence and Hellinger Distance to quantify differences between k-mer profiles.
• Distance Matrix and Phylogenetic Tree Generation: Produces a distance matrix and outputs a Newick tree file to represent evolutionary relationships among samples.
• Application to Next-Generation Sequencing Data: Processes raw DNA sequencing fastq files from multiple samples or time points for comparative analysis.

Scientific Applications:

• Estimating Tumor Heterogeneity: Quantifies spatial and temporal heterogeneity within patient cancer samples.
• Reconstructing Evolutionary Trajectories: Infers evolutionary relationships and trajectories among multiple tumor samples from the same patient.
• Longitudinal Cancer Studies: Applied to longitudinal next-generation sequencing cohorts, including glioma and clear cell renal cell carcinoma, to track progression over time.
• Origins of Metastasis and Recurrence: Supports identification of early events and potential origins of metastases and recurrences through comparative analysis.
• Unsupervised Genomic Profiling: Provides unsupervised assessment of patient genomic profiles using alignment-free metrics.

Methodology:

Reads raw fastq files, performs k-mer counting, computes Jensen-Shannon divergence and Hellinger Distance between k-mer profiles, generates a distance matrix and a Newick tree, and applies alignment-free phylogenetic classification approaches.