Automatic detection of fragile X chromosomes using an X centromere probe

Abstract

In order to score for the fragile X syndrome, blood samples are prepared with absorption stain labeling by in situ hybridisation of the X chromosome centromeres. Metaphases are located, digitised at high resolution, and segmented fully automatically. A three stage adaptive classification scheme for labeled X chromosomes is then applied. This consists of a simple box classifier to identify plausible X and false positive X chromosomes, followed by a quadratic discriminant classifier that is re-trained for each sample. The modal number of X chromosomes is then determined for each sample and used to refine the classification. A simple fragile site detector is applied to the distal portion of the detected X chromosome long arms. From the results we estimate computer and operator time requirements for a screening system in which the operator reviews only the apparently fragile X chromosomes detected by the computer.

Gene Technology: Applications and Techniques

“…Initially, RNA assays could reliably detect only rather abundant messages, using clone-derived probes (Lawrence and Singer, 1986). Enhancements in detection and computer processing algorithms have subsequently allowed detection of rare targets (Tanke et al, 1995;Piper et al, 1990Piper et al, , 1994. Advances in microscope and detector hardware have allowed the low light level produced by FISH to be recorded and analyzed with increasing sensitivity (Tanke et al, 1999).…”

Fluorescence in situ hybridization: past, present and future

“…Detection of DNA targets with large probes and the use of multi-color fluorescent cytometry algorithms (Galbraith et al, 1991) have allowed the production of automated mechanisms for assisting pathologists (Piper et al, 1994). In addition, the use of diagnostic probe sets and dotcounting approaches have yielded independent platforms capable of making simple diagnostic conclusions (Piper et al, 1990). Although methods have been introduced to analyze and optimize these cell classifiers (Castleman, 1985;Castleman and White, 1980;Castleman and White, 1981), manual cytopathology remains the gold standard for reliable tissue analysis, and automated mechanisms that can yield comparable data are still in development.…”