RNA viruses amino acid substitutions analysis

Environment

Create conda environment:

mamba env create -f environment.yml
mamba activate amino-acid-shift
pip install ete3 pytest PyYAML click legacy-cgi
pip install --no-deps pymutspec  # temporary solution until pymutspec is on conda-forge

Structure

1. SARS-CoV-2 amino acid substitutions ananlysis
2. RNA viruses mutational spectra derivation and analysis

Notebook	Short description	Outline
1sars-cov-2/1Neutral_scenario.ipynb	Neutral-model analyses: compute equilibrium freqs and compare models.
1sars-cov-2/2.1observed_sbs_fit.ipynb	Fit observed substitution patterns, compute fit metrics and plots.
1sars-cov-2/2.2fitness_analysis.ipynb	Analyze Δfitness of substitutions across clades using Bloom et al. data.
1sars-cov-2/2.3changes_during_COVID-19.ipynb	Analyze genotype data and changes during COVID-19 (genotypes2025).
1sars-cov-2/absorb_r2.ipynb	Analyze absorption metrics and R² relationships for model fits.
1sars-cov-2/model.ipynb	Model linking nucleotide mutation rates to expected AA substitutions.
1sars-cov-2/verify_model.ipynb	Verify equilibrium calculations (codon/AA level) and test stop-codon handling.
2other_viruses/1.1get_viruses_linages.ipynb	Extract viral taxonomy/lineages and select species for analyses.
2other_viruses/1get_viral_spectra_dataset.ipynb	Assemble viral spectra dataset (NEMU + Bloom) and tidy data.
2other_viruses/2spectra_eda_plus_eq_freq_be.ipynb	EDA of mutation spectra and equilibrium-frequency computations.
2other_viruses/2get_plot_ms12grouped_all_viruses.ipynb	Plot ms12 mutational spectra grouped by virus type/family.
2other_viruses/2get_cossim_between_nemu_Bloom.ipynb	Compute cosine similarity between NEMU dataset and Bloom et al. spectra.
2other_viruses/3pca.ipynb	PCA and classification of viral spectra; feature importance and clustering.
2other_viruses/3.2model_fit_quality.ipynb	Assess neutral-model fit quality and mutation summaries across viruses.
2other_viruses/4compare_aa_freqs_diff.ipynb	Compare AA frequency differences between viral groups and plot results.
2other_viruses/prepare_table_of_vir_info.ipynb	Build table of virus metadata and compute summary statistics for spectra.
2other_viruses/get_viruses_nucl_freq_aa_freq.ipynb	Compute amino-acid and nucleotide frequencies from viral reference sequences.
2other_viruses/get_viruses_nuc_and_aa_equilibrium_freq.ipynb	Compute nucleotide and AA equilibrium frequencies across viruses.
2other_viruses/get_plot_aa_observed_freq_vs_eq_freq.ipynb	Plot observed vs equilibrium amino-acid frequencies (per virus/group).
extra/human_germline.ipynb	Analyze human germline mutation spectra and per-gene AA equilibrium.
extra/nuc_eq_example.ipynb	Examples and calculations of nucleotide-equilibrium probabilities.
extra/random_spectra_thrend.ipynb	Random-spectrum simulations and their effect on equilibrium AA frequencies.
extra/rate_vs_freq.ipynb	Investigate relationships between mutation rates and observed frequencies.

6 --> 12 on aymmetric spectrum"

extra/nuc_eq_example.ipynb: "#### Cov20A (highly asymmetric)" extra/nuc_eq_example.ipynb: "#### aka spectrum (more symmetric)" extra/random_spectra_thrend.ipynb: "## Load rdrp freqs" extra/random_spectra_thrend.ipynb: "## Random spectra consequenses" extra/random_spectra_thrend.ipynb: "### Tests" extra/random_spectra_thrend.ipynb: "### Precalculated" extra/random_spectra_thrend.ipynb: "### CCA" extra/random_spectra_thrend.ipynb: "### PCA of amino acid freqs" extra/random_spectra_thrend.ipynb: "## Load RdRp amino acid freqs" -->

Data

data of Jesse D Bloom, Annabel C Beichman, Richard A Neher, Kelley Harris, Evolution of the SARS-CoV-2 Mutational Spectrum, Molecular Biology and Evolution, Volume 40, Issue 4, April 2023, msad085, https://doi.org/10.1093/molbev/msad085

• image of spectra https://jbloomlab.github.io/SARS2-mut-spectrum/rates-by-clade.html

• spectra table https://github.com/jbloomlab/SARS2-mut-spectrum/blob/main/results/synonymous_mut_rates/rates_by_clade.csv

• other viruses spectra https://github.com/jbloomlab/SARS2-mut-spectrum/blob/main/results/other_virus_spectra/other_virus_spectra.json

• Serratus database

References

• NAR paper about sars-cov-2 genome secondary structure
• sars-cov-2 replication paper 1 and 2
• sars-cov-2 life circle paper
• statistics decision tree pingouin
• sars-cov-2 variants
• Serratus database
• /refseq/release/viral
• NCBI Virus db