Tumor ploidy determination in low-pass whole genome sequencing and allelic copy number visualization using the Constellation Plot
Abstract Ploidy determination across the genome has been challenging for low-pass-WGS tumor-only samples. We present BACDAC, a method that calculates tumor ploidy down to 1.2X effective tumor coverage. Allele fraction patterns displayed in the Constellation Plot verify tumor ploidy and reveal subclo...
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| Format: | Article |
| Language: | English |
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BMC
2025-05-01
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| Series: | Genome Biology |
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| Online Access: | https://doi.org/10.1186/s13059-025-03599-2 |
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| author | Sarah H. Johnson James B. Smadbeck Roman M. Zenka Michael T. Barrett Athanasios Gaitatzes Arnav Solanki Angela B. Florio Mitesh J. Borad John C. Cheville George Vasmatzis |
| author_facet | Sarah H. Johnson James B. Smadbeck Roman M. Zenka Michael T. Barrett Athanasios Gaitatzes Arnav Solanki Angela B. Florio Mitesh J. Borad John C. Cheville George Vasmatzis |
| author_sort | Sarah H. Johnson |
| collection | DOAJ |
| description | Abstract Ploidy determination across the genome has been challenging for low-pass-WGS tumor-only samples. We present BACDAC, a method that calculates tumor ploidy down to 1.2X effective tumor coverage. Allele fraction patterns displayed in the Constellation Plot verify tumor ploidy and reveal subclonal populations. BACDAC outputs a metric, 2N+LOH, that when combined with ploidy better distinguishes near-diploid from high-ploidy tumors. Validated using TCGA, BACDAC had good agreement with other methods and 88% agreement with experimental methods. Discrepancies occur mainly when BACDAC predicts diploidy with subclones rather than high-ploidy. Applied to 653 low-pass-WGS samples spanning 12 cancer subtypes, BACDAC calls 40% as high-ploidy. |
| format | Article |
| id | doaj-art-c0753cd3aa0c4c15ae60e85cc6007a66 |
| institution | OA Journals |
| issn | 1474-760X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Genome Biology |
| spelling | doaj-art-c0753cd3aa0c4c15ae60e85cc6007a662025-08-20T02:29:51ZengBMCGenome Biology1474-760X2025-05-0126112210.1186/s13059-025-03599-2Tumor ploidy determination in low-pass whole genome sequencing and allelic copy number visualization using the Constellation PlotSarah H. Johnson0James B. Smadbeck1Roman M. Zenka2Michael T. Barrett3Athanasios Gaitatzes4Arnav Solanki5Angela B. Florio6Mitesh J. Borad7John C. Cheville8George Vasmatzis9Biomarker Discovery Program, Mayo ClinicBiomarker Discovery Program, Mayo ClinicQuantitative Health Sciences, Mayo ClinicHematology/Oncology, Mayo ClinicBiomarker Discovery Program, Mayo ClinicDepartment of Electrical and Computer Engineering, University of MinnesotaBiomarker Discovery Program, Mayo ClinicHematology/Oncology, Mayo ClinicBiomarker Discovery Program, Mayo ClinicBiomarker Discovery Program, Mayo ClinicAbstract Ploidy determination across the genome has been challenging for low-pass-WGS tumor-only samples. We present BACDAC, a method that calculates tumor ploidy down to 1.2X effective tumor coverage. Allele fraction patterns displayed in the Constellation Plot verify tumor ploidy and reveal subclonal populations. BACDAC outputs a metric, 2N+LOH, that when combined with ploidy better distinguishes near-diploid from high-ploidy tumors. Validated using TCGA, BACDAC had good agreement with other methods and 88% agreement with experimental methods. Discrepancies occur mainly when BACDAC predicts diploidy with subclones rather than high-ploidy. Applied to 653 low-pass-WGS samples spanning 12 cancer subtypes, BACDAC calls 40% as high-ploidy.https://doi.org/10.1186/s13059-025-03599-2Next generation sequencingPloidyWhole genome doublingLoss of heterozygosity |
| spellingShingle | Sarah H. Johnson James B. Smadbeck Roman M. Zenka Michael T. Barrett Athanasios Gaitatzes Arnav Solanki Angela B. Florio Mitesh J. Borad John C. Cheville George Vasmatzis Tumor ploidy determination in low-pass whole genome sequencing and allelic copy number visualization using the Constellation Plot Genome Biology Next generation sequencing Ploidy Whole genome doubling Loss of heterozygosity |
| title | Tumor ploidy determination in low-pass whole genome sequencing and allelic copy number visualization using the Constellation Plot |
| title_full | Tumor ploidy determination in low-pass whole genome sequencing and allelic copy number visualization using the Constellation Plot |
| title_fullStr | Tumor ploidy determination in low-pass whole genome sequencing and allelic copy number visualization using the Constellation Plot |
| title_full_unstemmed | Tumor ploidy determination in low-pass whole genome sequencing and allelic copy number visualization using the Constellation Plot |
| title_short | Tumor ploidy determination in low-pass whole genome sequencing and allelic copy number visualization using the Constellation Plot |
| title_sort | tumor ploidy determination in low pass whole genome sequencing and allelic copy number visualization using the constellation plot |
| topic | Next generation sequencing Ploidy Whole genome doubling Loss of heterozygosity |
| url | https://doi.org/10.1186/s13059-025-03599-2 |
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