Alternative Splicing Network Identification via Perturbation Analysis
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods lack an effective approach to identify functional associations between regulators of alternative splicing and compounds that can modulate these processes, particularly for disease therapy, due to the complexity of the splicing machinery and the intricate network of interactions involved.
Innovation Solution
A method is developed to generate a network of functional interactions among splicing regulation factors by perturbing alternative splicing conditions, assessing the impact on alternative splicing events, and constructing a network using algorithms like graphical lasso for identifying targets and potential drug candidates that interact with these factors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If current methods are used to identify functional associations between splicing regulators and compounds, then the complexity of the splicing machinery is maintained, but the ability to identify functional associations and drug targets is insufficient
Solution Approach 1:
The patent segments the complex splicing regulatory network into individual perturbation profiles, where each regulator's effect on alternative splicing events is measured separately. This allows the complex system to be analyzed in manageable units, enabling accurate identification of functional associations without being overwhelmed by the overall system complexity.
Solution Approach 2:
The patent introduces computational algorithms as intermediaries that process experimental data from splicing assays. These algorithms analyze perturbation profiles and construct interaction networks, serving as mediators between the complex biological system and the identification of functional associations, thereby improving measurement precision while managing complexity.
2Quantity of substance
If a comprehensive network of splicing interactions is constructed, then more functional associations can be identified, but the complexity of data processing and network construction increases
Solution Approach 1:
The patent performs preliminary perturbation assays for each splicing regulator before constructing the comprehensive network. By pre-measuring the effect of each regulator on alternative splicing events and creating individual perturbation profiles, the system prepares data in advance, enabling efficient network construction that identifies more functional associations without proportionally increasing processing complexity.
Solution Approach 2:
The patent transforms raw splicing data into standardized perturbation profiles using computational algorithms. This parameter transformation converts complex experimental measurements into comparable metrics, allowing the system to process and integrate data from multiple regulators efficiently, thereby identifying more functional associations while managing data processing complexity.
Data Source
Figure 1A~1D
Figure 1E~1I
Figure 2A~2B
AI summary
A method arising from knocking down the components of the splicing machinery on alternative splicing events relevant for cell proliferation and apoptosis and using this information to reconstruct a network of functional interactions. The network accurately captures known physical and functional associations and identifies new ones, revealing remarkable regulatory potential of core spliceosomal components. It can be used to infer targets for alternative splicing regulation and drugs directed to disease assocaited to altered splicing events.