INCISOR: An Algorithm to Identify Synthetic Rescue Mediators of Resistance to Targeted and Immunotherapy

Vizeacoumar, Frederick S.; Sahu, Avinash

doi:10.1007/978-1-0716-1740-3_11

Cited by 2 publications

(1 citation statement)

References 27 publications

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“…2B ). We previously published and validated a computational pipeline called ‘IdeNtification of ClinIcal Synthetic Rescues in cancer’ (INCISOR), which mines genomic, transcriptomic, and phenotypic data (such as patient survival) from hundreds of cancer patients and cell lines to identify DU-SR interactions that may be clinically relevant in patients 79,80 ( Methods ). INCISOR first identifies DU-SR interactions by mining hundreds of in vitro essentiality screens from cancer cell lines, and then filters those interactions by looking for positive selection and worsening survival association in patients’ tumors, and for interactions between gene pairs with high phylogenetic similarity across many divergent eukaryotic species 79 .…”

Section: Resultsmentioning

confidence: 99%

Chromosome 7 to the rescue: overcoming chromosome 10 loss in gliomas

Nair,

Schäffer,

Gertz

et al. 2024

Preprint

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The co-occurrence of chromosome 10 loss and chromosome 7 gain in gliomas is the most frequent loss-gain co-aneuploidy pair in human cancers, a phenomenon that has been investigated without resolution since the late 1980s. Expanding beyond previous gene-centric studies, we investigate the co-occurrence in a genome-wide manner taking an evolutionary perspective. First, by mining large tumor aneuploidy data, we predict that the more likely order is 10 loss followed by 7 gain. Second, by analyzing extensive genomic and transcriptomic data from both patients and cell lines, we find that this co-occurrence can be explained by functional rescue interactions that are highly enriched on 7, which can possibly compensate for any detrimental consequences arising from the loss of 10. Finally, by analyzing transcriptomic data from normal, non-cancerous, human brain tissues, we provide a plausible reason why this co-occurrence happens preferentially in cancers originating in certain regions of the brain.

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Section: Resultsmentioning

confidence: 99%

Chromosome 7 to the rescue: overcoming chromosome 10 loss in gliomas

Nair,

Schäffer,

Gertz

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

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Chromosome 7 Gain Compensates for Chromosome 10 Loss in Glioma

Nair,

Schäffer,

Gertz

et al. 2024

Cancer Research

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The co-occurrence of chromosome 10 loss and chromosome 7 gain in gliomas is the most frequent loss-gain co-aneuploidy pair in human cancers. This phenomenon has been investigated since the late 1980s without resolution. Expanding beyond previous gene-centric studies, we investigated the co-occurrence in a genome-wide manner taking an evolutionary perspective. Mining of large-scale tumor aneuploidy data confirmed the previous finding of a small-scale longitudinal study that the most likely order is chromosome 10 loss followed by chromosome 7 gain. Extensive analysis of genomic and transcriptomic data from both patients and cell lines revealed that this co-occurrence can be explained by functional rescue interactions that are highly enriched on chromosome 7, which could potentially compensate for any detrimental consequences arising from the loss of chromosome 10. Transcriptomic data from various normal, non-cancerous human brain tissues were analyzed to assess which tissues may be most predisposed to tolerate compensation of chromosome 10 loss by chromosome 7 gain. The analysis indicated that the pre-existing transcriptomic states in the cortex and frontal cortex, where gliomas arise, are more favorable than other brain regions for compensation by rescuer genes that are active on chromosome 7. Collectively, these findings suggest that the phenomenon of chromosome 10 loss and chromosome 7 gain in gliomas is orchestrated by a complex interaction of many genes residing within these two chromosomes and provide a plausible reason why this co-occurrence happens preferentially in cancers originating in certain regions of the brain.

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INCISOR: An Algorithm to Identify Synthetic Rescue Mediators of Resistance to Targeted and Immunotherapy

Cited by 2 publications

References 27 publications

Chromosome 7 to the rescue: overcoming chromosome 10 loss in gliomas

Chromosome 7 to the rescue: overcoming chromosome 10 loss in gliomas

Chromosome 7 Gain Compensates for Chromosome 10 Loss in Glioma

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