Clonal phylogenies inferred from bulk, single cell, and spatial transcriptomic analysis of epithelial cancers.
Epithelial cancers are typically heterogeneous with primary prostate cancer being a typical example of histological and genomic variation. Prior studies of primary prostate cancer tumour genetics revealed extensive inter and intra-patient genomic tumour heterogeneity. Recent advances in machine lear...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2025-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0316475 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841555607959633920 |
|---|---|
| author | Andrew Erickson Sandy Figiel Timothy Rajakumar Srinivasa Rao Wencheng Yin Dimitrios Doultsinos Anette Magnussen Reema Singh Ninu Poulose Richard J Bryant Olivier Cussenot Freddie C Hamdy Dan Woodcock Ian G Mills Alastair D Lamb |
| author_facet | Andrew Erickson Sandy Figiel Timothy Rajakumar Srinivasa Rao Wencheng Yin Dimitrios Doultsinos Anette Magnussen Reema Singh Ninu Poulose Richard J Bryant Olivier Cussenot Freddie C Hamdy Dan Woodcock Ian G Mills Alastair D Lamb |
| author_sort | Andrew Erickson |
| collection | DOAJ |
| description | Epithelial cancers are typically heterogeneous with primary prostate cancer being a typical example of histological and genomic variation. Prior studies of primary prostate cancer tumour genetics revealed extensive inter and intra-patient genomic tumour heterogeneity. Recent advances in machine learning have enabled the inference of ground-truth genomic single-nucleotide and copy number variant status from transcript data. While these inferred SNV and CNV states can be used to resolve clonal phylogenies, however, it is still unknown how faithfully transcript-based tumour phylogenies reconstruct ground truth DNA-based tumour phylogenies. We sought to study the accuracy of inferred-transcript to recapitulate DNA-based tumour phylogenies. We first performed in-silico comparisons of inferred and directly resolved SNV and CNV status, from single cancer cells, from three different cell lines. We found that inferred SNV phylogenies accurately recapitulate DNA phylogenies (entanglement = 0.097). We observed similar results in iCNV and CNV based phylogenies (entanglement = 0.11). Analysis of published prostate cancer DNA phylogenies and inferred CNV, SNV and transcript based phylogenies demonstrated phylogenetic concordance. Finally, a comparison of pseudo-bulked spatial transcriptomic data to adjacent sections with WGS data also demonstrated recapitulation of ground truth (entanglement = 0.35). These results suggest that transcript-based inferred phylogenies recapitulate conventional genomic phylogenies. Further work will need to be done to increase accuracy, genomic, and spatial resolution. |
| format | Article |
| id | doaj-art-78d50f162c4e4d0cb88428fdba7b7089 |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-78d50f162c4e4d0cb88428fdba7b70892025-01-08T05:31:42ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01201e031647510.1371/journal.pone.0316475Clonal phylogenies inferred from bulk, single cell, and spatial transcriptomic analysis of epithelial cancers.Andrew EricksonSandy FigielTimothy RajakumarSrinivasa RaoWencheng YinDimitrios DoultsinosAnette MagnussenReema SinghNinu PouloseRichard J BryantOlivier CussenotFreddie C HamdyDan WoodcockIan G MillsAlastair D LambEpithelial cancers are typically heterogeneous with primary prostate cancer being a typical example of histological and genomic variation. Prior studies of primary prostate cancer tumour genetics revealed extensive inter and intra-patient genomic tumour heterogeneity. Recent advances in machine learning have enabled the inference of ground-truth genomic single-nucleotide and copy number variant status from transcript data. While these inferred SNV and CNV states can be used to resolve clonal phylogenies, however, it is still unknown how faithfully transcript-based tumour phylogenies reconstruct ground truth DNA-based tumour phylogenies. We sought to study the accuracy of inferred-transcript to recapitulate DNA-based tumour phylogenies. We first performed in-silico comparisons of inferred and directly resolved SNV and CNV status, from single cancer cells, from three different cell lines. We found that inferred SNV phylogenies accurately recapitulate DNA phylogenies (entanglement = 0.097). We observed similar results in iCNV and CNV based phylogenies (entanglement = 0.11). Analysis of published prostate cancer DNA phylogenies and inferred CNV, SNV and transcript based phylogenies demonstrated phylogenetic concordance. Finally, a comparison of pseudo-bulked spatial transcriptomic data to adjacent sections with WGS data also demonstrated recapitulation of ground truth (entanglement = 0.35). These results suggest that transcript-based inferred phylogenies recapitulate conventional genomic phylogenies. Further work will need to be done to increase accuracy, genomic, and spatial resolution.https://doi.org/10.1371/journal.pone.0316475 |
| spellingShingle | Andrew Erickson Sandy Figiel Timothy Rajakumar Srinivasa Rao Wencheng Yin Dimitrios Doultsinos Anette Magnussen Reema Singh Ninu Poulose Richard J Bryant Olivier Cussenot Freddie C Hamdy Dan Woodcock Ian G Mills Alastair D Lamb Clonal phylogenies inferred from bulk, single cell, and spatial transcriptomic analysis of epithelial cancers. PLoS ONE |
| title | Clonal phylogenies inferred from bulk, single cell, and spatial transcriptomic analysis of epithelial cancers. |
| title_full | Clonal phylogenies inferred from bulk, single cell, and spatial transcriptomic analysis of epithelial cancers. |
| title_fullStr | Clonal phylogenies inferred from bulk, single cell, and spatial transcriptomic analysis of epithelial cancers. |
| title_full_unstemmed | Clonal phylogenies inferred from bulk, single cell, and spatial transcriptomic analysis of epithelial cancers. |
| title_short | Clonal phylogenies inferred from bulk, single cell, and spatial transcriptomic analysis of epithelial cancers. |
| title_sort | clonal phylogenies inferred from bulk single cell and spatial transcriptomic analysis of epithelial cancers |
| url | https://doi.org/10.1371/journal.pone.0316475 |
| work_keys_str_mv | AT andrewerickson clonalphylogeniesinferredfrombulksinglecellandspatialtranscriptomicanalysisofepithelialcancers AT sandyfigiel clonalphylogeniesinferredfrombulksinglecellandspatialtranscriptomicanalysisofepithelialcancers AT timothyrajakumar clonalphylogeniesinferredfrombulksinglecellandspatialtranscriptomicanalysisofepithelialcancers AT srinivasarao clonalphylogeniesinferredfrombulksinglecellandspatialtranscriptomicanalysisofepithelialcancers AT wenchengyin clonalphylogeniesinferredfrombulksinglecellandspatialtranscriptomicanalysisofepithelialcancers AT dimitriosdoultsinos clonalphylogeniesinferredfrombulksinglecellandspatialtranscriptomicanalysisofepithelialcancers AT anettemagnussen clonalphylogeniesinferredfrombulksinglecellandspatialtranscriptomicanalysisofepithelialcancers AT reemasingh clonalphylogeniesinferredfrombulksinglecellandspatialtranscriptomicanalysisofepithelialcancers AT ninupoulose clonalphylogeniesinferredfrombulksinglecellandspatialtranscriptomicanalysisofepithelialcancers AT richardjbryant clonalphylogeniesinferredfrombulksinglecellandspatialtranscriptomicanalysisofepithelialcancers AT oliviercussenot clonalphylogeniesinferredfrombulksinglecellandspatialtranscriptomicanalysisofepithelialcancers AT freddiechamdy clonalphylogeniesinferredfrombulksinglecellandspatialtranscriptomicanalysisofepithelialcancers AT danwoodcock clonalphylogeniesinferredfrombulksinglecellandspatialtranscriptomicanalysisofepithelialcancers AT iangmills clonalphylogeniesinferredfrombulksinglecellandspatialtranscriptomicanalysisofepithelialcancers AT alastairdlamb clonalphylogeniesinferredfrombulksinglecellandspatialtranscriptomicanalysisofepithelialcancers |