Most biology labs today—particularly smaller or early-career groups and those outside major funding hubs—face a tough reality: shrinking budgets, rising costs, limited access to cutting-edge technologies, and mounting pressures to publish. The challenge isn’t just keeping pace with innovation—it’s staying in the game at all. In this climate, simulation-first approaches are a powerful equalizer. By allowing scientists to test biological hypotheses computationally before committing to costly experiments, these tools enable smart science even on a tight budget.
Constraint often drives creativity. One strategy gaining momentum is AI-guided predictive modeling, which relies on data-driven tools that simulate biological behavior to unlock new insights. Built using advanced techniques like generative modeling (which simulates how a cell might respond to genetic or environmental changes) and probabilistic inference (which estimates the likelihood of different outcomes), these models are reshaping how we interpret complex data.
AI models are already used to forecast weather, simulate disease outbreaks, and model ecosystems. In single-cell biology, using programs such as CellOracle, scGen, and scVI, researchers can model how cells respond to perturbations, reprogramming, or developmental cues. Similarly, tools like DeepCell apply deep learning to image-based single-cell phenotyping, automating what used to require hours of manual microscopy. Meanwhile, AlphaFold has revolutionized structural biology by predicting protein structures in silico—compressing what once took months or years of lab work into minutes.
The trend is clear: AI is becoming a critical partner in formulating and refining biological hypotheses before stepping into the lab. These models often require large, high-quality training datasets to perform well, posing challenges for researchers working in under-sampled systems or with limited starting material. Even so, when good data are available, or we intentionally generate AI-compatible datasets, these tools offer a faster, more cost-effective way to ask complex biological questions, generate hypotheses, prioritize experiments, and deepen our understanding of biology.
Predictive modeling doesn’t replace wet lab experiments; it makes them sharper, faster, and smarter. This approach is already reshaping workflows. For example, Samantha Morris, a biologist at Harvard Medical School, and her team used CellOracle to computationally infer gene regulatory networks from single-cell multi-omics data and simulate transcription factor perturbations in silico, helping identify developmental regulators most worthy of experimental follow-up.1 This allowed them to predict key shifts in cell identity without performing initial perturbation experiments, which they later validated in the lab—demonstrating a powerful strategy for prioritizing follow-up studies while conserving time and resources. Similarly, Fabian Theis, director at HelmholtzAI, and his team created scGen to predict cellular responses to disease and drug treatments, providing a map of likely outcomes before costly screening.2 Like any model, AI tools are only as good as the data and assumptions behind them. Their predictions should guide, not replace, biological reasoning.
Beyond improving efficiency and experimental design, these AI-driven approaches are also compelling because they democratize access to powerful biological insights and to science in general. Once trained, researchers, even those with limited resources, can run these predictive models and generate predictions using public datasets. The Human Cell Atlas, for instance, offers comprehensive single-cell profiles across tissues and conditions, while Gene Expression Omnibus (GEO) hosts thousands of curated transcriptomic datasets. Tabula Sapiens provides a human cell-type atlas across multiple organs, a valuable reference for cross-tissue comparisons. These datasets, combined with pre-trained models, can power meaningful discovery even without needing immediate access to a physical lab or multi-million budgets.
While AI tools are powerful, they do require some tuning, context, and computational literacy, and are not yet entirely plug-and-play for all users. Barriers to widespread adoption remain, including steep learning curves, uncertainty in interpreting model predictions, and the disciplinary divide, marked by communication gaps, between experimental and computational scientists. But the single-cell biology landscape is evolving fast: Documentation is improving, community awareness and support are growing, and most tools include training tutorials.
Adoption of AI in biology also requires a cultural shift. Many biologists still view modeling as speculative or overly abstract. But with the growing integration of AI in biomedical science, learning to collaborate across disciplines—and to trust simulations as a complementary part of the research pipeline—can open new doors. Predictive modeling allows us not just to reduce redundancy or lower costs, but to ask smarter questions, explore rare or difficult systems, and build more reproducible, generalizable models of biology. It’s a way to work more strategically, inclusively, and sustainably.
Increasingly, biologists are recognizing that our ability to ask meaningful questions is no longer constrained by what we can measure—it’s constrained by what we can model. That “simulation-first science” sentiment captures a growing recognition: In the era of abundant data, insight comes from interpretation, not just generation.
Biology’s future is predictive, not just descriptive. AI-driven models connect raw data to meaningful insight, empowering researchers to ask smarter questions and make faster progress. In an era of shrinking budgets and expanding ambition, adopting these tools isn’t a luxury—it’s the new foundation of biological discovery.
- Kamimoto K, et al. Dissecting cell identity via network inference and in silico gene perturbation. Nature. 2023;614(7949):742–751.
- Lotfollahi M, et al. scGen predicts single-cell perturbation responses.Nat Methods. 2019;16(8):715-721.
