GIMscan: A new statistical method for analyzing whole-genome array CGH data

Genetic instability represents an important type of biological markers for cancer and many other diseases. Array Comparative Genome Hybridization (aCGH) is a high-throughput cytogenetic technique that can efficiently detect genorne-wide genetic instability events such as chromosomal gain, loss, and more complex aneuploidity, collectively known as genome imbalance (GIM). We propose a new statistical method, Genome Imbalance Scanner (GIMscan), for automatically decoding the underlying DNA dosage states from aCCH data. GIMscan captures both the intrinsic (nonrandom) spatial change of genome hybridization intensities, and the prevalent (random) measurement noise during data acquisition; and it simultaneously segments the chromosome and assigns different states to the segmented DNA. We tested the proposed method oil both simulated data and real data measured from a colorectal cancer population, and we report competitive or superior performance of GIMscan in comparison with popular extant methods.