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A mini-review on perturbation modelling across single-cell omic modalities
George I Gavriilidis1, Vasileios Vasileiou1,2, Aspasia Orfanou1
1Institute of Applied Biosciences, Centre for Research and Technology Hellas, Thessaloniki, Greece.
Summary
Single-cell perturbation modeling uses machine learning to understand how external factors affect cells. This review covers new technologies, computational methods, and future directions for this rapidly advancing field.
Area of Science:
- Cellular and Molecular Biology
- Computational Biology
- Genomics
Background:
- Single-cell omics technologies have advanced cellular characterization.
- Perturbation modeling aims to understand external influences on cellular physiology.
- Machine and deep learning are crucial for analyzing complex perturbational data.
Purpose of the Study:
- To review single-cell perturbation technologies and computational methods.
- To highlight challenges and future perspectives in the field.
- To provide a guide for researchers navigating this expanding area.
Main Methods:
- Review of genetic manipulation techniques (e.g., CRISPR) and compound-based perturbations.
- Survey of computational approaches including statistical inference, machine learning (shallow models, autoencoders), and gene regulatory networks.
- Discussion of foundational models and ensemble learning strategies.
Main Results:
- Summary of diverse single-cell perturbation technologies across omic modalities.
- Overview of a wide range of computational methods, from classical to deep learning and biologically informed approaches.
- Identification of emerging trends like large foundational models.
Conclusions:
- Single-cell perturbation modeling is a rapidly evolving field with significant potential.
- Future directions include perturbation atlases, multi-omics, spatial data, and causal machine learning.
- Addressing challenges in interpretability, interoperability, and benchmarking is crucial for future progress.

