Detection of low level genomic alterations by comparative genomic hybridization based on cDNA micro-arrays.
BACKGROUND
The accumulation of genomic alterations is an important process in tumor formation and progression. Comparative genomic hybridization performed on cDNA arrays (cDNA aCGH) is a common method to investigate the genomic alterations on a genome-wide scale. However, when detecting low-level DNA copy number changes this technology requires the use of noise reduction strategies due to a low signal to noise ratio.


RESULTS
Currently a running average smoothing filter is the most frequently used noise reduction strategy. We analyzed this strategy theoretically and experimentally and found that it is not sensitive to very low level genomic alterations. The presence of systematic errors in the data is one of the main reasons for this failure. We developed a novel algorithm which efficiently reduces systematic noise and allows for the detection of low-level genomic alterations. The algorithm is based on comparison of the biological relevant data to data from so-called self-self hybridizations, additional experiments which contain no biological information but contain systematic errors. We find that with our algorithm the effective resolution for +/-1 DNA copy number changes is about 2 Mb. For copy number changes larger than three the effective resolution is on the level of single genes.
Bilke
Sven
S
Oncogenomics Section, Pediatric Oncology Branch, Advanced Technology Center, National Cancer Institute 8717 Grovemont Circle, Gaithersburg, MD 20877, USA. bilkes@mail.nih.gov
Chen
Qing-Rong
QR
Whiteford
Craig C
CC
Khan
Javed
J
D000465:Algorithms; D002874:Chromosome Mapping / Q000379:methods*; D004252:DNA Mutational Analysis / Q000379:methods*; D018628:Gene Dosage; D020869:Gene Expression Profiling / Q000379:methods*; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods*; D008957:Models, Genetic; D015233:Models, Statistical; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009447:Neuroblastoma / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D009363:Neoplasm Proteins