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Abstract

Grant Number:	5R44HD038150-03
PI Name:	MERCHANT, FATIMA
PI Email:	merchant@persci.com
PI Title:	LEAD RESEARCH ENGINEER
Project Title:	Improved Imaging for Precise Crytpic Anomaly Detection

Abstract: DESCRIPTION (provided by applicant): This project will further develop automated instrumentation and image analysis techniques to detect cryptic chromosomal rearrangements, which are difficult to detect by conventional cytogenetics. It combines two innovative FISH probes: "SubTelomeric" (STFISH) and "Multiplex" (MFISH), with sophisticated image analysis, for screening patients developmental disabilities. During the Phase I project, we evaluated the feasibility of (1) performing automated identification of chromosome metaphases, and (2) using sophisticated image analysis for accurate detection of submicroscopic rearrangements. We also compared the efficiency and precision of the two FISH techniques for cryptic rearrangement detection. We analyzed 8 samples using STFISH, and 6 samples using MFISH. Our experimental results show that, the use of STFISH probes ranging in size from 300Kbp to 30Mbp, permitted the delineation of chromosomal rearrangements in 8/10 samples. The remaining 2 samples were considered half-cryptic, since the Subtelomeric probe set does not contain a chromosome specific probe for the p-arm of chromosome 22. Therefore, the satellites from 22p could not be identified with the telomere probe set. The MFISH assay was effective in detecting chromosomal rearrangements in 3/6 cases of which 2 were half-cryptic, and one had a 3-way rearrangement, including a 5Mbp insertion. We developed software components for an automated system, including auto focusing, slide scanning for 24 well slides (CytocellTM), and metaphase finding. Finally, we estimated the cost and time savings achievable, by the addition of improved imaging methods to both the FISH techniques. In Phase II, we will further develop the technology and test it in a clinical environment. Specifically, for MFISH we will optimize the software for enhanced performance in detecting rearrangements. For STFISH, we will (1) determine the scanning and metaphase finding rates of the automated system, (2) test the prototype in a clinical environment; and (3) evaluate the commercial feasibility of the instrument. Phase 3 will then make this new technology available for commercialization.

Thesaurus Terms:
biomedical automation, biomedical equipment development, chromosome translocation, digital imaging, gene rearrangement, genetic disorder diagnosis, genetic screening, microscopy
computer data analysis, computer program /software, computer system design /evaluation, developmental disease /disorder, mental retardation, nucleic acid probe, telomere
bioimaging /biomedical imaging, clinical research, fluorescent in situ hybridization, human genetic material tag, human tissue

Institution:	ADVANCED DIGITAL IMAGING RESEARCH, LLC
	2450 S SHORE BLVD, STE 305
	LEAGUE CITY, TX 775732997
Fiscal Year:	2003
Department:
Project Start:	27-SEP-1999
Project End:	30-APR-2004
ICD:	NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
IRG:	ZRG1

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