PMID- 33570999 OWN - NLM STAT- MEDLINE DCOM- 20210831 LR - 20240210 IS - 2473-4276 (Electronic) IS - 2473-4276 (Linking) VI - 5 DP - 2021 Feb TI - FrenchFISH: Poisson Models for Quantifying DNA Copy Number From Fluorescence In Situ Hybridization of Tissue Sections. PG - 176-186 LID - 10.1200/CCI.20.00075 [doi] LID - CCI.20.00075 AB - 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. FAU - Macintyre, Geoff AU - Macintyre G AD - Cancer Research UK, Cambridge Institute, University of Cambridge, Cambridge, UK. FAU - Piskorz, Anna M AU - Piskorz AM AD - Cancer Research UK, Cambridge Institute, University of Cambridge, Cambridge, UK. FAU - Berman, Adam AU - Berman A AD - Cancer Research UK, Cambridge Institute, University of Cambridge, Cambridge, UK. FAU - Ross, Edith AU - Ross E AD - Cancer Research UK, Cambridge Institute, University of Cambridge, Cambridge, UK. FAU - Morse, David B AU - Morse DB AD - Cancer Research UK, Cambridge Institute, University of Cambridge, Cambridge, UK. AD - Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge, UK. FAU - Yuan, Ke AU - Yuan K AD - University of Glasgow, Glasgow, UK. FAU - Ennis, Darren AU - Ennis D AD - Institute of Cancer Sciences, University of Glasgow, Glasgow, UK. AD - Department of Surgery and Cancer, Imperial College London, UK. FAU - Pike, Jeremy A AU - Pike JA AD - Cancer Research UK, Cambridge Institute, University of Cambridge, Cambridge, UK. AD - Centre of Membrane Proteins and Receptors (COMPARE), Universities of Birmingham and Nottingham, UK. FAU - Goranova, Teodora AU - Goranova T AD - Cancer Research UK, Cambridge Institute, University of Cambridge, Cambridge, UK. FAU - McNeish, Iain A AU - McNeish IA AD - Institute of Cancer Sciences, University of Glasgow, Glasgow, UK. AD - Department of Surgery and Cancer, Imperial College London, UK. FAU - Brenton, James D AU - Brenton JD AD - Cancer Research UK, Cambridge Institute, University of Cambridge, Cambridge, UK. FAU - Markowetz, Florian AU - Markowetz F AD - Cancer Research UK, Cambridge Institute, University of Cambridge, Cambridge, UK. LA - eng GR - C14303/A17197/CRUK_/Cancer Research UK/United Kingdom GR - A18072/CRUK_/Cancer Research UK/United Kingdom GR - 28290/CRUK_/Cancer Research UK/United Kingdom GR - A19274/CRUK_/Cancer Research UK/United Kingdom GR - 19274/CRUK_/Cancer Research UK/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - JCO Clin Cancer Inform JT - JCO clinical cancer informatics JID - 101708809 RN - 9007-49-2 (DNA) SB - IM MH - *Chromosome Aberrations MH - Computer Simulation MH - DNA MH - *DNA Copy Number Variations/genetics MH - Humans MH - In Situ Hybridization, Fluorescence PMC - PMC8140799 EDAT- 2021/02/12 06:00 MHDA- 2021/09/01 06:00 PMCR- 2022/02/11 CRDT- 2021/02/11 17:12 PHST- 2021/02/11 17:12 [entrez] PHST- 2021/02/12 06:00 [pubmed] PHST- 2021/09/01 06:00 [medline] PHST- 2022/02/11 00:00 [pmc-release] AID - CCI.20.00075 [pii] AID - 10.1200/CCI.20.00075 [doi] PST - ppublish SO - JCO Clin Cancer Inform. 2021 Feb;5:176-186. doi: 10.1200/CCI.20.00075.