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The flow of genetic information in cells from DNA to mRNA to protein is described by the central dogma, which states that genes specify the sequence of mRNAs, which in turn specify the sequence of amino acids making up all proteins. The decoding of one molecule to another is performed by specific proteins and RNAs. Because the information stored in DNA is so central to cellular function, it makes intuitive sense that the cell would make mRNA copies of this information for protein synthesis...
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cdsBERT - Extending Protein Language Models with Codon Awareness.

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Summary
This summary is machine-generated.

Protein language models (pLMs) now incorporate codon information, enhancing protein analysis. This codon-based approach, cdsBERT, improves predictions by capturing subtle sequence variations.

Keywords:
Artificial intelligenceBERTCodon usage biasMELDMachine learningProtein language model

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Area of Science:

  • Bioinformatics
  • Computational Biology
  • Genomics

Background:

  • Protein language models (pLMs) analyze protein sequences for high-throughput studies.
  • Codon usage bias is increasingly recognized for its predictive power in protein structure and function.

Approach:

  • Extended pLM vocabulary from amino acids to codons within CoDing Sequences (CDS).
  • Developed a novel pipeline (MELD) using token embedding seeding, masked language modeling, and knowledge distillation.
  • Transformed ProtBERT into cdsBERT, a codon-based pLM trained on a large CDS corpus.

Key Points:

  • cdsBERT variants generated a biochemically relevant latent space, outperforming amino acid-based models in enzyme commission number prediction.
  • Synonymous codon embeddings showed distinct movements, indicating information in "silent" mutations across phylogeny.
  • Embedding movement correlated with average usage bias, highlighting the significance of codon choice.

Conclusions:

  • Codon-based pLMs offer a novel way to improve protein structure and function prediction.
  • Future organism-specific codon pLMs could enhance codon usage fidelity.
  • Creating a codon pLM foundation model and enriching protein databases with CDS is crucial for advancing the field.