ArticleBriefings in bioinformatics2024
Synthetic lethal connectivity and graph transformer improve synthetic lethality prediction.
Article in Briefings in bioinformatics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Explainable/interpretable artificial intelligence and knowledge graph neural network for synthetic lethality prediction: overview, challenges, and future directions.Briefings in bioinformatics · 2026Review
- Context-dependent synthetic lethality - an emerging precision therapeutic approach.Nature reviews. Cancer · 2026Review
- A Synthetic Lethality-Informed Multi-Omic Framework for Identifying a Five-Gene Diagnostic Signature in Chronic Obstructive Pulmonary Disease.Current issues in molecular biology · 2026Article
- Deep Learning-Enabled Multi-Omics Integration: A New Frontier in Precise Drug Target Discovery.Biology · 2026Review
- Synthetic lethality in cancer therapy: Mechanisms, models and clinical translation for overcoming therapeutic resistance.Clinical and translational medicine · 2026Review
- Integrating artificial intelligence across the cancer drug discovery pipeline using a design-test-refine workflow.Frontiers in oncology · 2026Review
- MGANSL: multi-network representation generating with generative adversarial network for synthetic lethality prediction.BMC bioinformatics · 2025Article
- A multi-layer encoder prediction model for individual sample specific gene combination effect (MLEC-iGeneCombo).PLoS computational biology · 2025Article
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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. However, lack of scalable SL properties prevents generalizability of SL interactions to out-of-sample data, thereby hindering modeling efforts. In this paper, we recognize that SL connectivity is a scalable and generalizable SL property. We develop a novel two-step multilayer encoder for individual sample-specific SL prediction model (MLEC-iSL), which predicts SL connectivity first and SL interactions subsequently. MLEC-iSL has three encoders, namely, gene, graph, and transformer encoders. MLEC-iSL achieves high SL prediction 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. The prediction performance of MLEC-iSL is validated in a CDKO experiment in 22Rv1 cells, yielding a 46.8% SL rate among 987 selected gene pairs. The screen also reveals SL dependency between apoptosis and mitosis cell death pathways.
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