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Multimodal Modeling of CRISPR-Cas12 Activity Using Foundation Models and Chromatin Accessibility Data

Published: June 12, 2025 | arXiv ID: 2506.11182v1

By: Azim Dehghani Amirabad , Yanfei Zhang , Artem Moskalev and more

Potential Business Impact:

Helps gene editing tools work better and faster.

Business Areas:
Bioinformatics Biotechnology, Data and Analytics, Science and Engineering

Predicting guide RNA (gRNA) activity is critical for effective CRISPR-Cas12 genome editing but remains challenging due to limited data, variation across protospacer adjacent motifs (PAMs-short sequence requirements for Cas binding), and reliance on large-scale training. We investigate whether pre-trained biological foundation model originally trained on transcriptomic data can improve gRNA activity estimation even without domain-specific pre-training. Using embeddings from existing RNA foundation model as input to lightweight regressor, we show substantial gains over traditional baselines. We also integrate chromatin accessibility data to capture regulatory context, improving performance further. Our results highlight the effectiveness of pre-trained foundation models and chromatin accessibility data for gRNA activity prediction.

Page Count
8 pages

Category
Quantitative Biology:
Genomics