Promoter Calculator cuts design from hours to minutes without DNALMs, sparking EVO2 debate
anshulkundaje · x · 2026-10-31
- Hsalis team's latest Promoter Calculator designs sequences with target transcription rates for 6 sigma factors and 10+ design rules, shrinking hours of classic optimization to minutes—no DNALM involved.
- Anshul Kundaje doubts purely self-supervised DNALMs (like EVO2) will be the best samplers for regulatory DNA and proposes a head-to-head benchmark against simpler methods with Brian Hie's team.
- Hsalis argues the real test is multi-objective optimization: efficient generators must satisfy motif rules without iterating, bias toward objective functions, and use model predictions to find minimal edits.
- A notable AI-for-Science debate: big generative models vs classical optimization.
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