Methods for determining absolute genome-wide copy number variations of complex tumors

Abstract

Methods for interpreting absolute copy number of complex tumors and for determining the copy number of a genomic region at a detection position of a target sequence in a sample are disclosed. In certain aspects, genomic regions of a target sequence in a sample are sequenced and measurement data for sequence coverage is obtained. Sequence coverage bias is corrected and may be normalized against a baseline sample. Hidden Markov Model (HMM) segmentation, scoring, and output are performed, and in some embodiments population-based no-calling and identification of low-confidence regions may also be performed. A total copy number value and region-specific copy number value for a plurality of regions are then estimated.

Description

[0001] related application [0002] This application is a continuation-in-part of and claims priority to U.S. Application Serial No. 13 / 270,989, filed October 11, 2011, which claims U.S. Provisional Patent Application No. 61 / 503,327, filed June 30, 2011, and 2010 Priority to U.S. Provisional Patent Application No. 61 / 392,567, filed October 13, 2009. This application also claims priority to US Provisional Patent Application Serial No. 61 / 643,225, filed May 4, 2012. The entire contents of each of them are incorporated by reference into this application in their entirety as if fully set forth herein. Background of the invention [0003] Genomic abnormalities are often associated with various genetic and degenerative diseases, as well as cancer. For example, loss or gain of gene copies and deletion or amplification of genomic segments or specific regions are not uncommon in cancer. For example, alterations in proto-oncogenes and tumor suppressor genes, respectively, are common ...

AI Technical Summary

Problems solved by technology

In these methods, copy number identification and its confirmation are based on different sample series

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