PubMed · 4481569
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L S Khutorova. 1972. [Riboflavin mononucleotide].. https://pubmed.ncbi.nlm.nih.gov/4481569/
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Recent advances in large language models have extended to genomic applications, yet model robustness relative to context is unclear. Here, we demonstrate two intrinsic biases (input sequence length and nucleotide position) affecting SegmentNT results, a model included with the Nucleotide Transformer that provides nucleotide-level predictions of biological features. We demonstrate that nucleotide position within the input sequence (beginning, middle, or end) alters the nature of SegmentNT's raw prediction probabilities, which can be standardized to improve prediction consistency. While longer input sequence length improves model performance, diminishing returns suggest a surprisingly small input length of ∼3072 nucleotides might be sufficient for many applications. We further identify a 24-nucleotide periodic oscillation in SegmentNT's prediction probabilities, revealing an intrinsic bias potentially linked to the model's training tokenization (6-mers) and architecture. We identify potential approaches to account for these biases and provide generalizable insights for utilizing nucleotide-resolution functional prediction models.
The nucleoside triphosphates 1, containing a photochemically cleavable group, and 2, having one that may be cleaved via palladium catalysis, were prepared as a prelude to investigating sequencing of DNA via sequencing by synthesis.
The anticodon domain of lysine transfer ribonucleic acid (tRNA) is a model system for investigation of the structural and biochemical effects of nucleoside posttranscriptional modification. To enable detailed study of the biophysical and structural effects of hypermodified nucleosides, methods have been developed to synthesize RNA oligonucleotides containing the modified nucleosides found in lysine tRNA. We describe in detail the synthesis of protected phosphoramidites of the nucleosides methylaminomethyl-2-thiouridine (mnm5s2U), methylcarboxymethyl-2-thiouridine (mcm5s2U), and 2-thiomethyl-N-6-carbamoylthreonyl-adenosine (ms2t6A). We also describe methods for using these nucleoside phosphoramidite reagents to synthesize RNA oligonucleotides with modified nucleosides incorporated at the specific sequence locations corresponding to their positions in the native lysine tRNAs.