FrenchFISH: Poisson Models for Quantifying DNA Copy Number From Fluorescence In Situ Hybridization of Tissue Sections
| Autor: | Edith M. Ross, Darren Ennis, Florian Markowetz, Teodora Goranova, David B. Morse, Ke Yuan, James D. Brenton, Jeremy A. Pike, Adam G. Berman, Anna M. Piskorz, Iain A. McNeish, Geoff Macintyre |
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| Přispěvatelé: | Imperial College Healthcare NHS Trust- BRC Funding, Cancer Research UK, Ovarian Cancer Action |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
DNA Copy Number Variations Tumor cells Poisson distribution 01 natural sciences 010104 statistics & probability 03 medical and health sciences chemistry.chemical_compound symbols.namesake medicine Humans 1112 Oncology and Carcinogenesis Computer Simulation Oncology & Carcinogenesis 0101 mathematics In Situ Hybridization Fluorescence Chromosome Aberrations medicine.diagnostic_test Cancer 1103 Clinical Sciences General Medicine Gold standard (test) DNA medicine.disease Molecular biology 030104 developmental biology Tissue sections chemistry symbols Fluorescence in situ hybridization |
| Zdroj: | JCO clinical cancer informatics. 5 |
| ISSN: | 2473-4276 |
| Popis: | PURPOSE Chromosomal aberration and DNA copy number change are robust hallmarks of cancer. The gold standard for detecting copy number changes in tumor cells is fluorescence in situ hybridization (FISH) using locus-specific probes that are imaged as fluorescent spots. However, spot counting often does not perform well on solid tumor tissue sections due to partially represented or overlapping nuclei. MATERIALS AND METHODS To overcome these challenges, we have developed a computational approach called FrenchFISH, which comprises a nuclear volume correction method coupled with two types of Poisson models: either a Poisson model for improved manual spot counting without the need for control probes or a homogeneous Poisson point process model for automated spot counting. RESULTS We benchmarked the performance of FrenchFISH against previous approaches using a controlled simulation scenario and tested it experimentally in 12 ovarian carcinoma FFPE-tissue sections for copy number alterations at three loci (c-Myc, hTERC, and SE7). FrenchFISH outperformed standard spot counting with 74% of the automated counts having < 1 copy number difference from the manual counts and 17% having < 2 copy number differences, while taking less than one third of the time of manual counting. CONCLUSION FrenchFISH is a general approach that can be used to enhance clinical diagnosis on sections of any tissue by both speeding up and improving the accuracy of spot count estimates. |
| Databáze: | OpenAIRE |
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