A probe-density-based analysis method for array CGH data: simulation, normalization and centralization.
BACKGROUND
Genomic instability is one of the fundamental factors in tumorigenesis and tumor progression. Many studies have shown that copy-number abnormalities at the DNA level are important in the pathogenesis of cancer. Array comparative genomic hybridization (aCGH), developed based on expression microarray technology, can reveal the chromosomal aberrations in segmental copies at a high resolution. However, due to the nature of aCGH, many standard expression data processing tools, such as data normalization, often fail to yield satisfactory results.


RESULTS
We demonstrated a novel aCGH normalization algorithm, which provides an accurate aCGH data normalization by utilizing the dependency of neighboring probe measurements in aCGH experiments. To facilitate the study, we have developed a hidden Markov model (HMM) to simulate a series of aCGH experiments with random DNA copy number alterations that are used to validate the performance of our normalization. In addition, we applied the proposed normalization algorithm to an aCGH study of lung cancer cell lines. By using the proposed algorithm, data quality and the reliability of experimental results are significantly improved, and the distinct patterns of DNA copy number alternations are observed among those lung cancer cell lines.


BACKGROUND
Source codes and.gures may be found at http://ntumaps.cgm.ntu.edu.tw/aCGH_supplementary.
Chen
Hung-I Harry
HI
Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan 106, Republic of China.
Hsu
Fang-Han
FH
Jiang
Yuan
Y
Tsai
Mong-Hsun
MH
Yang
Pan-Chyr
PC
Meltzer
Paul S
PS
Chuang
Eric Y
EY
Chen
Yidong
Y
D001483:Base Sequence; D002874:Chromosome Mapping / Q000379:methods*; D003198:Computer Simulation; D015342:DNA Probes / Q000235:genetics*; D018628:Gene Dosage / Q000235:genetics*; D008957:Models, Genetic; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D016415:Sequence Alignment / Q000379:methods*; D017422:Sequence Analysis, DNA / Q000379:methods*
D015342:DNA Probes