TITAN (CNA/LOH clonal inference)

Overview

TITAN is a probabilistic model for inferring subclonal copy number alterations (CNAs) and loss of heterozygosity (LOH) from tumour whole-genome sequencing data. It jointly models allele-specific copy number and cellular prevalence, producing clonal CNA profiles that can be compared with SNV-based clonal assignments (e.g., from PyClone) to confirm or refute clonal architecture inferences.

Used by

• Used for CNA/LOH clonal inference in breast cancer PDX clonal-dynamics study; TITAN-based CNA clonal dynamics recapitulated SNV-based PyClone dynamics in minor-subclone expansion (SA494, SA495, SA532, SA533) and polyclonal engraftment (SA493, SA501), providing orthogonal validation of clonal selection at engraftment PMID:25470049
• Used for allele-specific copy-number analysis in whole-genome sequencing of matched primary/recurrent medulloblastoma samples; revealed increased structural-variant burden at recurrence and enabled detection of focal events like MYC-locus chromothripsis acquired only at recurrence PMID:26760213.

Notes

• Requires whole-genome sequencing input (allele count data and read depth).
• Outputs clonal and subclonal CNA segments with associated cellular prevalence estimates.
• Frequently used alongside PyClone (SNV clustering) for multi-modal clonal analysis.

Sources

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