Predicting transcriptional outcomes of novel multigene perturbations with GEARS
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Abstract
Understanding cellular responses to genetic perturbation is central to numerous biomedical applications, from identifying genetic interactions involved in cancer to developing methods for regenerative medicine. However, the combinatorial explosion in the number of possible multigene perturbations severely limits experimental interrogation. Here, we present graph-enhanced gene activation and repression simulator (GEARS), a method that integrates deep learning with a knowledge graph of gene-gene relationships to predict transcriptional responses to both single and multigene perturbations using single-cell RNA-sequencing data from perturbational screens. GEARS is able to predict outcomes of perturbing…
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Authors
3Topics & keywords
Topics
Keywords
- Gene
- Computational biology
- Graph
- Perturbation (astronomy)
- Psychological repression
- Biology
- Computer science
- Gene expression
UN Sustainable Development Goals
- Good health and well-being
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Funding
- NSNational Science FoundationAwards: 1934578, 1835598, 1918940
- GGlaxoSmithKline
- NINational Institutes of Health
- DADefense Advanced Research Projects AgencyAwards: HR00112190039, N660011924033
- MUMultidisciplinary University Research Initiative
- WTWu Tsai Neurosciences Institute, Stanford University
- CFCenter for Information TechnologyAward: 3U54HG010426-04S1
- ARArmy Research OfficeAwards: W911NF-16-1, W911NF-16-1-0342, W911NF-16-1-, W911NF