Search arXiv⌕ Search

arXiv · 0708.2038

Genome landscapes and bacteriophage codon usage

Abstract

Across all kingdoms of biological life, protein-coding genes exhibit unequal usage of synonmous codons. Although alternative theories abound, translational selection has been accepted as an important mechanism that shapes the patterns of codon usage in prokaryotes and simple eukaryotes. Here we analyze patterns of codon usage across 74 diverse bacteriophages that infect E. coli, P. aeruginosa and L. lactis as their primary host. We introduce the concept of a `genome landscape,' which helps reveal non-trivial, long-range patterns in codon usage across a genome. We develop a series of randomization tests that allow us to interrogate the significance of one aspect of codon usage, such a GC content, while controlling for another aspect, such as adaptation to host-preferred codons. We find that 33 phage genomes exhibit highly non-random patterns in their GC3-content, use of host-preferred codons, or both. We show that the head and tail proteins of these phages exhibit significant bias towards host-preferred codons, relative to the non-structural phage proteins. Our results support the hypothesis of translational selection on viral genes for host-preferred codons, over a broad range of bacteriophages.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Julius B. Lucks, David R. Nelson, Grzegorz Kudla, Joshua B. Plotkin. 2007-08-14. Genome landscapes and bacteriophage codon usage. https://doi.org/10.1371/journal.pcbi.1000001

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related papers

Motif-Vocab: StatisticallyCalibrated Transcription-Factor-Identity Tokenization forGenomic Language Models

Tokenization is a central design choice in genomic language models, yet most deoxyribonucleic acid (DNA) tokenizers use characters, fixed-length k-mers, or frequency-derived subwords without explicitly using prior information about the specificity of DNA-binding regulatory factors. We introduce Motif-Vocab, a biologically informed tokenizer that scans both DNA strands for statistically calibrated motif matches, emits transcription-factor (TF) identity tokens, and applies nucleotide, $k$-mer, or byte-pair encoding (BPE) to unmatched sequence. Motif-specific null distributions put position-weight matrices (PWMs) of different lengths and degeneracy on a common significance scale; deterministic overlap rules make the representation reproducible. In controlled Bidirectional Encoder Representations from Transformers (BERT) pretraining on two billion base pairs, real motif libraries outperform randomized-motif controls on 54 of 55 in-scope downstream tasks. On a motif-disjoint recognition task derived from DART-Eval Task 2, TF-specific tokens improve macro-F1 by 0.040 over a position-matched generic motif token and by 0.033 over a matched no-motif tokenizer (95\% bootstrap confidence interval: 0.027--0.038). Motif tokens also receive stronger attribution and produce larger occlusion effects than shuffled controls. Dense no-motif tokenizers remain strong general-purpose baselines, including a near-tie on the five-task BERT-base panel. Thus, Motif-Vocab is not a universal accuracy replacement; it is a targeted, interpretable inductive bias for motif-sensitive genomic modeling.

q-bio.GN↗

Revolutionizing Genomics with Reinforcement Learning Techniques

In recent years, Reinforcement Learning (RL) has emerged as a powerful tool for solving a wide range of problems, including decision-making and genomics. The exponential growth of raw genomic data over the past two decades has exceeded the capacity of manual analysis, leading to a growing interest in automatic data analysis and processing. RL algorithms are capable of learning from experience with minimal human supervision, making them well-suited for genomic data analysis and interpretation. One of the key benefits of using RL is the reduced cost associated with collecting labeled training data, which is required for supervised learning. While there have been numerous studies examining the applications of Machine Learning (ML) in genomics, this survey focuses exclusively on the use of RL in various genomics research fields, including gene regulatory networks (GRNs), genome assembly, and sequence alignment. We present a comprehensive technical overview of existing studies on the application of RL in genomics, highlighting the strengths and limitations of these approaches. We then discuss potential research directions that are worthy of future exploration, including the development of more sophisticated reward functions as RL heavily depends on the accuracy of the reward function, the integration of RL with other machine learning techniques, and the application of RL to new and emerging areas in genomics research. Finally, we present our findings and conclude by summarizing the current state of the field and the future outlook for RL in genomics.

q-bio.GN↗

Transcriptomic Models for Immunotherapy Response Prediction Show Limited Cross-cohort Generalisability

Immune checkpoint inhibitors (ICIs) have transformed cancer therapy; yet substantial proportion of patients exhibit intrinsic or acquired resistance, making accurate pre-treatment response prediction a critical unmet need. Transcriptomics-based biomarkers derived from bulk and single-cell RNA sequencing (scRNA-seq) offer a promising avenue for capturing tumour-immune interactions, yet the cross-cohort generalisability of existing prediction models remains unclear.We systematically benchmark nine state-of-the-art transcriptomic ICI response predictors, five bulk RNA-seq-based models (COMPASS, IRNet, NetBio, IKCScore, and TNBC-ICI) and four scRNA-seq-based models (PRECISE, DeepGeneX, Tres and scCURE), using publicly available independent datasets unseen during model development. Overall, predictive performance was modest: bulk RNA-seq models performed at or near chance level across most cohorts, while scRNA-seq models showed only marginal improvements. Pathway-level analyses revealed sparse and inconsistent biomarker signals across models. Although scRNA-seq-based predictors converged on immune-related programs such as allograft rejection, bulk RNA-seq-based models exhibited little reproducible overlap. PRECISE and NetBio identified the most coherent immune-related themes, whereas IRNet predominantly captured metabolic pathways weakly aligned with ICI biology. Together, these findings demonstrate the limited cross-cohort robustness and biological consistency of current transcriptomic ICI prediction models, underscoring the need for improved domain adaptation, standardised preprocessing, and biologically grounded model design.

q-bio.GN↗