Accurate Identification of Significant Aberrations in Cancer Genome: Implementation and Applications

Somatic Copy Number Alterations (CNAs) are common events in human cancers. Identifying CNAs and Significant Copy number Aberrations (SCAs) in cancer genomes is a critical task in searching for cancer-associated genes. Advanced genome profiling technologies, such as SNP array technology, facilitate copy number study at a genome-wide scale with high resolution. However, due to normal tissue contamination, the observed intensity signals are actually the mixture of copy number signals contributed from both tumor and normal cells. This genetic confounding factor would significantly affect the subsequent copy number analyses. In order to accurately identify significant aberrations in contaminated cancer genome, we develop a Java AISAIC package (Accurate Identification of Significant Aberrations in Cancer) that incorporates recent novel algorithms in the literature, BACOM (Bayesian Analysis of Copy number Mixtures) and SAIC (Significant Aberrations in Cancer). Specifically, BACOM is used to estimate the normal tissue contamination fraction and recover the "true" copy number profiles. And SAIC is used to detect SCAs using large recovered tumor samples. Considering the popularity of modern multi-core computers and clusters, we adopt concurrent computing using Java Fork/Join API to speed up the analysis. We evaluate the performance of the AISAIC package in both empirical family-wise type I error rate and detection power on a large number of simulation data, and get promising results. Finally, we use AISAIC to analyze real cancer data from TCGA portal and detect many SCAs that not only cover majority of reported cancer-associated genes, but also some novel genome regions that may worth further study.

Name thesis:degree_name

Master of Science

Level thesis:degree_level

masters

Discipline thesis:degree_discipline

Computer Engineering

Department dc:contributor.department

Electrical and Computer Engineering

Grantor dc:publisher

Virginia Tech

Year dc:date.issued

2013

Author dc:creator

• Hou, Xuchu

Chair dc:contributor.committeechair

• Wang, Yue J.

Committee members dc:contributor.committeemember

• Ozcan, Ibrahim Alpay
• Yu, Guoqiang

• Copy Number Alterations
• Normal Tissue Contamination
• Significant Copy number Aberrations
• Concurrent Computing

Statement dc:rights

• In Copyright

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Dc Identifier Other

vt_gsexam:207

OAI identifier oai:identifier

oai:vtechworks.lib.vt.edu:10919/19235