PRODE recovers essential and context-essential genes through neighborhood-informed scores
Abstract Gene context-essentiality assessment supports precision oncology opportunities. The variability of gene effects inference from loss-of-function screenings across models and technologies limits identifying robust hits. We propose a computational framework named PRODE that integrates gene eff...
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| Format: | Article |
| Language: | English |
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BMC
2025-02-01
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| Series: | Genome Biology |
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| Online Access: | https://doi.org/10.1186/s13059-025-03501-0 |
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| author | Thomas Cantore Paola Gasperini Riccardo Bevilacqua Yari Ciani Sanju Sinha Eytan Ruppin Francesca Demichelis |
| author_facet | Thomas Cantore Paola Gasperini Riccardo Bevilacqua Yari Ciani Sanju Sinha Eytan Ruppin Francesca Demichelis |
| author_sort | Thomas Cantore |
| collection | DOAJ |
| description | Abstract Gene context-essentiality assessment supports precision oncology opportunities. The variability of gene effects inference from loss-of-function screenings across models and technologies limits identifying robust hits. We propose a computational framework named PRODE that integrates gene effects with protein–protein interactions to generate neighborhood-informed essential (NIE) and neighborhood-informed context essential (NICE) scores. It outperforms the canonical gene effect approach in recovering missed essential genes in shRNA screens and prioritizing context-essential hits from CRISPR-KO screens, as supported by in vitro validations. Applied to Her2 + breast cancer tumor samples, PRODE identifies oxidative phosphorylation genes as vulnerabilities with prognostic value, highlighting new therapeutic opportunities. |
| format | Article |
| id | doaj-art-da711a5ae0d643f09f471554ed076cec |
| institution | DOAJ |
| issn | 1474-760X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Genome Biology |
| spelling | doaj-art-da711a5ae0d643f09f471554ed076cec2025-08-20T03:04:34ZengBMCGenome Biology1474-760X2025-02-0126112610.1186/s13059-025-03501-0PRODE recovers essential and context-essential genes through neighborhood-informed scoresThomas Cantore0Paola Gasperini1Riccardo Bevilacqua2Yari Ciani3Sanju Sinha4Eytan Ruppin5Francesca Demichelis6Laboratory of Computational and Functional Oncology, Department of Cellular, Computational, and Integrative Biology, University of TrentoLaboratory of Computational and Functional Oncology, Department of Cellular, Computational, and Integrative Biology, University of TrentoLaboratory of Computational and Functional Oncology, Department of Cellular, Computational, and Integrative Biology, University of TrentoLaboratory of Computational and Functional Oncology, Department of Cellular, Computational, and Integrative Biology, University of TrentoCancer Data Science Laboratory (CDSL), Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH)Cancer Data Science Laboratory (CDSL), Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH)Laboratory of Computational and Functional Oncology, Department of Cellular, Computational, and Integrative Biology, University of TrentoAbstract Gene context-essentiality assessment supports precision oncology opportunities. The variability of gene effects inference from loss-of-function screenings across models and technologies limits identifying robust hits. We propose a computational framework named PRODE that integrates gene effects with protein–protein interactions to generate neighborhood-informed essential (NIE) and neighborhood-informed context essential (NICE) scores. It outperforms the canonical gene effect approach in recovering missed essential genes in shRNA screens and prioritizing context-essential hits from CRISPR-KO screens, as supported by in vitro validations. Applied to Her2 + breast cancer tumor samples, PRODE identifies oxidative phosphorylation genes as vulnerabilities with prognostic value, highlighting new therapeutic opportunities.https://doi.org/10.1186/s13059-025-03501-0EssentialityContext-essentialityGene effectPPICancer vulnerabilitiesNeighborhood-informed scores |
| spellingShingle | Thomas Cantore Paola Gasperini Riccardo Bevilacqua Yari Ciani Sanju Sinha Eytan Ruppin Francesca Demichelis PRODE recovers essential and context-essential genes through neighborhood-informed scores Genome Biology Essentiality Context-essentiality Gene effect PPI Cancer vulnerabilities Neighborhood-informed scores |
| title | PRODE recovers essential and context-essential genes through neighborhood-informed scores |
| title_full | PRODE recovers essential and context-essential genes through neighborhood-informed scores |
| title_fullStr | PRODE recovers essential and context-essential genes through neighborhood-informed scores |
| title_full_unstemmed | PRODE recovers essential and context-essential genes through neighborhood-informed scores |
| title_short | PRODE recovers essential and context-essential genes through neighborhood-informed scores |
| title_sort | prode recovers essential and context essential genes through neighborhood informed scores |
| topic | Essentiality Context-essentiality Gene effect PPI Cancer vulnerabilities Neighborhood-informed scores |
| url | https://doi.org/10.1186/s13059-025-03501-0 |
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