Graph transformer guided synthetic lethality prediction
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1094989 | ENA |
REPOSITORIES: ENA
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Project description:Synthetic lethality (SL) has shown great promise for the discovery of novel targets in cancer. CRISPR double-knockout (CDKO) technologies can only screen several hundred genes and their combinations, but not genome-wide. Therefore, good SL prediction models are highly needed for genes and gene pairs selection in CDKO experiments. In this paper, we develop a novel multi-layer encoder for individual sample-specific SL prediction (MLEC-iSL). Unlike existing SL prediction models, MLEC-iSL is built to predict SL connectivity first. Because SL connectivity is scalable from existing genes in the training data to new genes in validation data, we hypothesize MLEC-iSL has better SL prediction performance. MLEC-iSL has three encoders, namely gene encoder, graph encoder, and transformer encoder. MLEC-iSL has high performance in K562 (AUPR, 0.73; AUC, 0.72) and Jurkat (AUPR, 0.73; AUC, 0.71) cells while no existing methods exceed 0.62 AUPR and AUC in either cell. MLEC-iSL guided CDKO experiment in 22Rv1 cells yielded a 46.8% SL ratio amongst its selected gene pairs. Six of top ten SL connectivity hub genes are validated in 22Rv1 cells. It reveals SL gene pairs and dependency between apoptosis and mitosis cell death pathways.
2024-09-13 | GSE262953 | GEO
Project description:Assessment of synthetic lethality between an sml1 null mutation and Yeast Deletion mutations Keywords = SML1 Keywords = yeast Keywords = deletion Keywords = synthetic lethality Keywords = tag Keywords = barcode Keywords: repeat sample
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Project description:Assessment of synthetic lethality between an sgs1 null mutation and Yeast Deletion mutations Keywords = SGS1 Keywords = yeast Keywords = deletion Keywords = synthetic lethality Keywords = tag Keywords = barcode Keywords: repeat sample
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Project description:Assessment of synthetic lethality between a bim1 null mutation and Yeast Deletion mutations Keywords = BIM1 Keywords = yeast Keywords = deletion Keywords = synthetic lethality Keywords = tag Keywords = barcode Keywords: repeat sample
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Project description:Assessment of synthetic lethality between a cin8 deletion mutation and Yeast Deletion mutations. Keywords = CIN8 Keywords = yeast Keywords = deletion Keywords = synthetic lethality Keywords = tag Keywords = barcode Keywords: repeat sample
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Project description:Synthetic lethality is a type of genetic interaction in which two non-lethal mutations acting together result in a loss of viability. Such interactions are important for the insights they may offer into how gene functions are organized into distinct cellular processes. The datasets in this Series represent an effort to identify synthetic lethal genetic interactions in the yeast Saccharomyces cerevisiae on a genome-wide scale. Please see the Pubmed IDs in the individual Sample annotations.
2013-02-28 | E-GEOD-14217 | biostudies-arrayexpress
Project description:Obtain synthetic lethality/slow growth gene interactors of acs2-Ts8 Keywords: gene mutation
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Project description:Synthetic lethality by TET-dioxygenase inhibition
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