ITALICS

ITALICS performs iterative normalization and copy-number calling to improve accuracy of DNA copy number measurements from Affymetrix SNP arrays.

Key Features:

• Array compatibility: Operates on Affymetrix SNP arrays containing between 11,000 and 500,000 SNP probes.
• Iterative normalization: Employs an iterative normalization procedure to separate biologically relevant copy-number variation from non-biological variation.
• Joint estimation of effects: Alternates between estimating biological and non-biological effects to remove irrelevant variation and enhance signal for copy number calling.
• Copy-number calling: Calls DNA copy number states from normalized probe intensities.
• Performance validation: Demonstrated improved performance relative to existing normalization methods on several in-house datasets and a public dataset.
• Experimental validation: Quantitative PCR (qPCR) validation confirmed correspondence between ITALICS copy number calls and true genomic alterations.

Scientific Applications:

• Cancer research: Localizes genomic copy number alterations for studies of tumor genomes and oncogenic events.
• Copy number polymorphism studies: Measures DNA copy number variation for analyses of genetic diversity and polymorphisms.

Methodology:

Alternates iterative normalization steps that estimate biological and non-biological effects to refine copy number calls from Affymetrix SNP array probe intensities.