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Predicting dynamic expression patterns in budding yeast with a fungal DNA language model.

Kuan-Hao Chao1,2, Majed Magzoub3, Emily Stoops3

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Summary
This summary is machine-generated.

We developed Shorkie, a novel DNA language model, to predict gene expression from DNA sequences. This model significantly enhances gene expression prediction and regulatory network analysis by leveraging evolutionary pretraining and transfer learning.

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Area of Science:

  • Genomics
  • Computational Biology
  • Molecular Biology

Background:

  • Predicting gene expression from DNA sequence is complex due to intricate regulatory mechanisms.
  • Understanding gene regulation is crucial for deciphering noncoding variants and biological networks.

Purpose of the Study:

  • To develop a model that improves gene expression prediction from DNA sequence.
  • To identify and analyze regulatory grammar and motif usage in gene regulation.
  • To accurately predict the effects of genetic variants on gene expression.

Main Methods:

  • Pretraining a masked DNA language model on 165 fungal genomes.
  • Fine-tuning the language model on yeast RNA-seq data, including time-course induction experiments.
  • Evaluating the model's performance in gene expression prediction, cis-eQTL classification, and reporter assays.

Main Results:

  • Shorkie substantially improved gene expression prediction compared to baseline models.
  • The model identified conserved transcription factor binding motifs and their usage dynamics.
  • Shorkie accurately predicted variant effects, outperforming existing sequence-to-expression models.

Conclusions:

  • Evolutionary-scale pretraining combined with transfer learning enhances the decoding of gene regulation from sequence.
  • Shorkie provides valuable insights into noncoding variants and regulatory network dynamics.
  • The framework offers a powerful approach for understanding promoter dynamics, splicing, and motif usage.