Other

Cytognomix Inc.

Peter Keith Rogan

Yanxin Li

Joan Helen Knoll

Jin Liu

Jagath Samarabandu

Akila Subasinghe

Automation of microscopic pathological diagnosis relies on digital image quality, which, in turn, affects the rates of false positive and negative cellular objects designated as abnormalities. Cytogenetic biodosimetry is a genotoxic assay that detects dicentric chromosomes (DCs) arising from exposure to ionizing radiation. The frequency of DCs is related to radiation dose received, so the inferred radiation dose depends on the accuracy of DC detection. To improve this accuracy, image segmentation methods are used to rank high quality cytogenetic images and eliminate suboptimal metaphase cell data in a sample based on novel quality measures. When sufficient numbers of high quality images are found, the microscope system is directed to terminate metaphase image collection for a sample. The International Atomic Energy Agency recommends at least 500 images be used to estimate radiation dose, however often many more images are collected in order to select the metaphase cells with good morphology for analysis. Improvements in DC recognition increase the accuracy of dose estimates, by reducing false positive (FP) DC detection. A set of chromosome morphology segmentation methods selectively filtered out false DCs, arising primarily from extended prometaphase chromosomes, sister chromatid separation and chromosome fragmentation. This reduced FPs by 55% and was highly specific to the abnormal structures (&#x2265;97.7%). Additional procedures were then developed to fully automate image review, resulting in 6 image-level filters that, when combined, selectively remove images with consistently unparsable or incorrectly segmented chromosome morphologies. Overall, these filters can eliminate half of the FPs detected by manual image review. Optimal image selection and FP DCs are minimized by combining multiple feature based segmentation filters and a novel image sorting procedure based on the known distribution of chromosome lengths. Consequently, the average dose estimation error was reduced from 0.4 Gy to &#x3c;0.2 Gy with minimal manual review required. Automated image selection with these filters reduces the number of images that are required to capture metaphase cells, thus decreasing the number of images and time required for each sample. A microscope system integrates image selection procedures controls with an automated digitally controlled microscope then determines at what point a sufficient number of metaphase cell images have been acquired to accurately determine radiation dose, which then terminates data collection by the microscope. These image filtering approaches constitute a reliable and scalable solution that results in more accurate and rapid radiation dose estimates.

Smart microscope system for radiation biodosimetry

An automated microscope system is described that detects dicentric chromosomes (DCs) in metaphase cells arising from exposure to ionizing radiation. The radiation dose depends on the accuracy of DC detection. Accuracy is increased using image segmentation methods are used to rank high quality cytogenetic images and eliminate suboptimal metaphase cell data in a sample based on novel quality measures. When a sufficient number of high quality images are detected, the microscope system is directed to terminate metaphase image collection for a sample. The microscope system integrates image selection procedures that control an automated digitally controlled microscope with the analysis of acquired metaphase cell images to accurately determine radiation dose. Early termination of image acquisition reduces sample processing time without compromising accuracy. This approach constitutes a reliable and scalable solution that will be essential for analysis of large numbers of potentially exposed individuals.

A method for determining genes in breast cancer that are stable in copy number, expression and sequence in tumors from nearly all patients. Certain stable genes are targets of standard chemotherapy. The effectiveness of therapies that act upon these targets depends on maintaining the stability and integrity of these genes in tumors. Mutations in these targets result in poor response to therapies that target these gene products. In the instant invention, ordinarily stable gene targets are characterized as either normal or mutant for the purpose of determining whether to include or exclude particular drugs as potential treatments.

Stable gene targets in breast cancer and use thereof for optimizing therapy

A method for determining radiation exposure from chromosome abnormalities present in a specimen by determining the location or locations of the centromere of each chromosome in a cell in an image of a metaphase cell by segmentation of an accurately drawn chromosome centerline followed by selection of a longitudinal cross-section with the minimum width or intensity or width and intensity; counting the number of centromeres in each chromosome in each cell; computing the frequency of dicentric chromosomes in a population of cells; and determining the radiation dose by comparing the computed frequency of dicentric chromosomes with a previously determined dose-response curve from a calibrated source.

Centromere detector and method for determining radiation exposure from chromosome abnormalities

An improved method for rapid identification of microorganisms is disclosed, along with sequences of PCR primers optimized for this purpose. The primers are designed based on information analysis of sequences from a large number of organism to amplify certain segments of genomic DNA whose sequences are unique among different organisms. The PCR products are compared with a DNA sequence database to obtain the identity of the microorganisms. This approach provides an accurate and fast identification and taxonomic assignment of microbial species.

Rapid and comprehensive identification of prokaryotic organisms by metagenomic analysis

Single copy sequences suitable for use as DNA probes can be defined by computational analysis of genomic sequences. The present invention provides an ab initio method for identification of single copy sequences for use as probes which obviates the need to compare genomic sequences with existing catalogs of repetitive sequences. By dividing a target reference sequence into a series of shorter contiguous sequence windows and comparing these sequences with the reference genome sequence, one can identify single copy sequences in a genome. Probes can then be designed and produced from these single copy intervals.

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London, Canada

Peter Keith Rogan