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Systematic Analysis of Genetic Alterations in Tumors Using Cancer
Genome WorkBench (CGWB)
Jinghui Zhang
National Cancer Institute, NIH
Lecture Hall, New Life Science Building, PKU
1:30-2:30pm, Mon, 26 June
Abstract
Systematic investigations of genetic changes in tumors such as The
Cancer Genome Atlas (TCGA) project are expected to lead to
understanding of cancer etiology. To meet informatics challenges
presented by these studies, we developed the Cancer Genome WorkBench
(http://cgwb.nci.nih.gov ). The CGWB is an integrated computational
platform able to 1) provide comprehensive mutation analysis using
our novel algorithms SNPdetector and IndelDetector; 2) construct
clinical mutation profiles and integrate them with the reference
human genome in our web-based Cancer Genome Browser; 3) permit
visual inspection of results; 4) annotate the effects of genetic
alteration on protein coding and 3D structure. The ability of the
system to facilitate identifying genetic alterations is illustrated
in two studies. Mutagenesis in tumor DNA replication leading to
complex genetic changes in the EGFR kinase domain is suggested by a
somatic deletion-insertion-combination observed in paired
tumor-normal lung cancer resquencing data. Also in lung cancer, loss
of the normal allele and mutational inactivation of the second
allele is suggested by analysis of the tumor suppressor gene
LKB1. Automated analysis of 152 genes resequenced by the SeattleSNPs
group was able to identify 90% of the 1,251 insertion/deletion
polymorphisms manually discovered by SeattleSNPs. In addition, CGWB
discovered 623 novel insertion/deletion polymorphisms with a 90%
validation rate, a 40% increase in insertion/deletion polymorphism
markers in this data set. The CGWB is the first analytical system
that integrates the patient mutation profiles with genomic
information. Our experience demonstrates that using this system not
only greatly improves the productivity and the accuracy of mutation
identification but through its data integration and visualization
capabilities facilities identification of underlying genetic
etiology.
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