SCONE

SCONE assesses evolutionary conservation at nucleotide (base-pair) resolution to quantify selective pressures acting on individual bases in the human genome.

Key Features:

• Base-Pair Resolution Conservation Scoring: Scores conservation at individual base-pair resolution to enable granular assessment of evolutionary dynamics.
• Rate Estimation and Neutrality Probability: Estimates the evolutionary rate for each nucleotide and computes the probability of neutrality, combining these into a SCONE score that quantifies conservation per base.
• Correlation with Human Polymorphisms: SCONE scores correlate with allele frequencies of human polymorphisms across both coding and noncoding regions.
• Analysis Beyond Canonical Conserved Regions: Identifies conserved nucleotides that lie outside longer, traditionally identified conserved elements and that show signatures of ongoing selection in allele frequency spectra.
• Functional Region Enrichment: Reveals enrichment of individually conserved positions and short (<15 bp) conserved sequences ("chunks") within functional genomic regions.

Scientific Applications:

• Predicting Functional Significance: Identifies nucleotides under selective pressure to aid prediction of the functional impact of genetic variation.
• Cis-Regulatory Sequence Analysis: Analyzes sequence substructure of cis-regulatory elements and other functional genomic regions.
• Understanding Evolutionary Dynamics: Provides insights into the evolutionary history and ongoing selection pressures acting on the human genome.

Methodology:

Integrates high-quality sequence data from up to 23 genomes to compute per-nucleotide conservation scores across approximately 1% of the human genome, reflecting historical and contemporary evolutionary pressures.