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During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
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Initiating translation is complex because it involves multiple molecules. Initiator tRNA, ribosomal subunits, and eukaryotic initiation factors (eIFs) are all required to assemble on the initiation codon of mRNA. This process consists of several steps that are mediated by different eIFs.
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Extending Protein Language Models to a Viral Genomic Scale Using Biologically Induced Sparse Attention.

Thibaut Dejean1, Barbra D Ferrell2, William Harrigan3

  • 1Department of Information and Computer Sciences, University of Hawaii, Honolulu, HI.

Biorxiv : the Preprint Server for Biology
|June 12, 2025
PubMed
Summary
This summary is machine-generated.

We developed a novel protein language model that analyzes entire viral genomes, capturing long-range interactions. This genome-wide approach significantly improves protein sequence analysis compared to single-protein models.

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Area of Science:

  • Genomics
  • Deep Learning
  • Bioinformatics

Background:

  • Transformer models have advanced protein sequence analysis.
  • Current protein language models typically analyze individual proteins, neglecting genomic context.
  • Protein-protein interactions are crucial and span genomic regions.

Purpose of the Study:

  • To develop a novel protein language model with extended context size across entire viral genomes.
  • To capture long-range interprotein interactions and integrate information from distant proteins within a genome.
  • To improve protein sequence analysis by considering genomic context.

Main Methods:

  • Proposed a novel approach extending transformer models' context size to entire viral genomes.
  • Employed a sparse attention mechanism based on protein-protein interactions.
  • Utilized a semi-supervised approach for training on sequences up to 61,000 amino acids.

Main Results:

  • The genome-wide protein language model captures long-range interprotein interactions.
  • Generated embeddings significantly surpass those from single-protein models.
  • Outperformed alternative large-context architectures and non-transformer frameworks.

Conclusions:

  • Training protein language models on entire viral genomes is effective for capturing interprotein dependencies.
  • The proposed long-context model offers substantial benefits for various protein analysis tasks.
  • This genome-wide learning approach addresses limitations of single-protein analysis.