Splicescope: a computational software for determining cellular states using RNA splicing profiles

This technology is a computational method, named Splicescope, for identifying the specific cell type, differentiation, and maturation of a cell using its RNA splicing profile data.

Unmet Need: Method to evaluate in vitro differentiation and maturation of stem cell derived neurons

While methods for differentiation of stem cells into neurons in vitro have been developed, much information about the cell’s current state of development and splicing information is not available. This information is critical to determine the robustness of a differentiation protocol, examine the cell’s development and ability to function as desired, and understand the differential splicing of the induced cells. There are currently no available methods to capture the relevant maturation states of the cells in development without neglecting key data that can be derived from the RNA splicing profiles of the cells.

The Technology: Computational method to determine cell maturation and development using RNA splicing data

This computational method, named Splicescope, uses whole transcriptome data to compute RNA splicing information in order to determine cell types and the stage of differentiation for the cell. Alternative splicing data can be indicative of developmentally regulated changes and contribute to the differentiation of cells into a specific cell type. This information is captured using Splicescope and is integrated into the program to predict the cell’s maturation state. With this software, the challenging differentiation of cells like neurons in vitro can be further evaluated and characterized after long term cultures. Splicescope has also shown the ability to determine potential pathways and specific exons involved in the developmental advancements between stages. As a result, this technology provides an improved method for determining cellular states with a highly flexible framework.

Applications:

• Determine cell maturation states after in vitro culture
• Monitor long-term neuronal culture
• Evaluate the functional relevance of stem cell derived neurons
• Understand the overall mechanism and splicing data for differentiation
• Evaluate deviations in the cell transcriptome in diseased cells

Advantages:

• Uses whole transcriptome data to infer cellular states
• Can identify variation in exon expressions otherwise missed by whole gene expression analysis
• Can be used to validate differentiation protocols
• Determine which cell groups can be used for treatment based on functionality
• Further improved to evaluate specific neuronal subtypes

Lead Inventor:

Chaolin Zhang, Ph.D.

Patent Information:

Patent Pending

Related Publications:

• Jacko M, Weyn-Vanhentenryck SM, Smerdon JW, Yan R, Feng H, Williams DJ, Pai J, Xu K, Wichterle H, Zhang C. “Rbfox splicing factors promote neuronal maturation and axon initial segment assembly” Neuron. 2018 Feb 21;97(4):853-868.

• Weyn-Vanhentenryck, SM, Feng, H, Ustianenko D, Duffié R, Yan Q, Jacko Q, Martinez JC, Goodwin M, Zhang X, Hengst U, Lomvardas S, Swanson MS, Zhang C. “Precise temporal regulation of alternative splicing during neural development” Nat Commun. 2018 Jan; 9: 2189.

Tech Ventures Reference:

• IR CU17194

• Licensing Contact: Ron Katz