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Published on: August 25, 2023
Multi-omics approach to identifying isoform variants as therapeutic targets in cancer patients
Timothy I Shaw1, Bi Zhao2, Yuxin Li3
1Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, United States.
Abstract:
Cancer-specific alternatively spliced events (ASE) play a role in cancer pathogenesis and can be targeted by immunotherapy, oligonucleotide therapy, and small molecule inhibition. However, identifying actionable ASE targets remains challenging due to the uncertainty of its protein product, structure impact, and proteoform (protein isoform) function. Here we argue that an integrated multi-omics profiling strategy can overcome these challenges, allowing us to mine this untapped source of targets for therapeutic development. In this review, we will provide an overview of current multi-omics strategies in characterizing ASEs by utilizing the transcriptome, proteome, and state-of-art algorithms for protein structure prediction. We will discuss limitations and knowledge gaps associated with each technology and informatics analytics. Finally, we will discuss future directions that will enable the full integration of multi-omics data for ASE target discovery.
Insights
Identifying cancer-specific alternatively spliced events (ASEs) is challenging but crucial for developing new therapies. An integrated multi-omics approach can unlock these targets for drug development.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Cancer-specific alternatively spliced events (ASEs) are implicated in cancer development.
- Targeting ASEs offers potential for novel cancer therapies, including immunotherapy and small molecule inhibition.
- Identifying actionable ASE targets is hindered by challenges in predicting protein products, structural impacts, and proteoform functions.
Purpose of the Study:
- To review current multi-omics strategies for characterizing ASEs.
- To highlight limitations and knowledge gaps in existing technologies and analytical methods.
- To discuss future directions for integrating multi-omics data in ASE target discovery.
Main Methods:
- Utilizing transcriptome and proteome data for ASE characterization.
- Employing state-of-the-art algorithms for protein structure prediction.
- Integrating multi-omics data through advanced informatics analytics.
Main Results:
- Multi-omics profiling provides a comprehensive strategy to overcome challenges in identifying actionable ASE targets.
- Current technologies and algorithms offer insights into ASEs but have associated limitations.
- Further integration of multi-omics data is needed for robust ASE target discovery.
Conclusions:
- An integrated multi-omics approach is essential for unlocking the therapeutic potential of cancer-specific ASEs.
- Addressing current technological and analytical gaps will facilitate the discovery of novel ASE-based cancer treatments.
- Future research should focus on synergistic integration of multi-omics data for comprehensive ASE target identification.
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