Computer-aided imaging systems are now widely used in cytogenetic laboratories to reduce the tedium and labour-intensiveness of traditional methods of chromosome analysis. Automatic chromosome classification is an essential component of such systems, and we review here the statistical techniques that have contributed towards it. Although completely error-free classification has not been, nor is ever likely to be, achieved, error rates have been reduced to levels that are acceptable for many routine purposes. Further reductions are likely to be achieved through advances in basic biology rather than in statistical methodology. Nevertheless, the subject remains of interest to those involved in statistical classification, because of its intrinsic challenges and because of the large body of existing results with which to compare new approaches. Also, the existence of very large databases of correctly-classified chromosomes provides a valuable resource for empirical investigations of the statistical properties of classifiers.

Computer-aided classification of human chromosomes: a review

Mass casualty scenarios of radiation exposure require high throughput biological dosimetry techniques for population triage in order to rapidly identify individuals who require clinical treatment. The manual dicentric assay is a highly suitable technique, but it is also very time consuming and requires well trained scorers. In the framework of the MULTIBIODOSE EU FP7 project, semi-automated dicentric scoring has been established in six European biodosimetry laboratories. Whole blood was irradiated with a Co-60 gamma source resulting in 8 different doses between 0 and 4.5Gy and then shipped to the six participating laboratories. To investigate two different scoring strategies, cell cultures were set up with short term (2-3h) or long term (24h) colcemid treatment. Three classifiers for automatic dicentric detection were applied, two of which were developed specifically for these two different culture techniques. The automation procedure included metaphase finding, capture of cells at high resolution and detection of dicentric candidates. The automatically detected dicentric candidates were then evaluated by a trained human scorer, which led to the term 'semi-automated' being applied to the analysis. The six participating laboratories established at least one semi-automated calibration curve each, using the appropriate classifier for their colcemid treatment time. There was no significant difference between the calibration curves established, regardless of the classifier used. The ratio of false positive to true positive dicentric candidates was dose dependent. The total staff effort required for analysing 150 metaphases using the semi-automated approach was 2 min as opposed to 60 min for manual scoring of 50 metaphases. Semi-automated dicentric scoring is a useful tool in a large scale radiation accident as it enables high throughput screening of samples for fast triage of potentially exposed individuals. Furthermore, the results from the participating laboratories were comparable which supports networking between laboratories for this assay.

Automatic scoring of dicentric chromosomes as a tool in large scale radiation accidents

Motivations are presented for exploring formal statistical methods for use in medical diagnosis and the advantages and disadvantages are discussed. A brief review is presented of classical linear discriminant analysis, quadratic discriminant analysis, logistic regression, nearest neighbour and kernel methods, recursive partitioning methods, the independence model, regularized discriminant analysis, structured conditional probability distributions, methods for categorical data, and other methods. Criteria on which a choice might be made are presented and methods for assessing diagnostic performance are outlined. Particular applications of screening and chromosome analysis are used as illustrations and available software is described.

Statistical methods in diagnosis

Purpose: Automated detection of dicentric chromosomes from a large number of cells was applied to study age-dependent radiosensitivity after in vitro CT exposure of blood from healthy donorsMateri

/pdf/automated-scoring-of-dicentric-chromosomes-differentiates-4b34w869li.pdf

Automated scoring of dicentric chromosomes differentiates increased radiation sensitivity of young children after low dose CT exposure in vitro.

Full automation on the scoring of radiation-induced chromosomal aberrations in conventionally stained metaphase spreads cannot be achieved reliably due to the complex image analysis problems involved. More success may be obtained by using in situ hybridization staining of the chromosomes. We describe the development of a system to detect metaphases on the basis of a fluorescent counterstain and subsequently analyze the number of translocations with the aid of whole chromosome paints fluorescing in a different colour. The system consists of a Macintosh IIfx computer, an automated Ergolux microscope equipped for fluorescence, and a Sony CCD camera. The performance of the metaphase finder was measured on a small set of slides counterstained with DAPI, whereas the suitability of the system for scoring aberrations was tested in a small feasibility study for the detection or radiation-induced translocations involving chromosome 4. The potentialities of the system for the use of multiple colours are discussed.

A system for fluorescence metaphase finding and scoring of chromosomal translocations visualized by in situ hybridization.

http://link.springer.com/content/pdf/10.1007/978-3-642-74738-0_3.pdf

An Automated Chromosome Aberration Scoring System

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An Automated Chromosome Aberration Scoring System