Combining detection and reconstruction of correlational and periodic motifs in viral genomic sequences with transitional genome mapping: Application to COVID-19

Abstract

A method of Transitional Automorphic Mapping of the Genome on Itself (TAMGI) is aimed at combining detection and reconstruction of correlational and quasi-periodic motifs in the viral genomic RNA/DNA sequences. The motifs reconstructed by TAMGI are robust with respect to indels and point mutations and can be tried as putative therapeutic targets. We developed and tested the relevant theory and statistical criteria for TAMGI applications. The applications of TAMGI are illustrated by the study of motifs in the genomes of the severe acute respiratory syndrome coronaviruses SARS-CoV and SARS-CoV-2 (the latter coronavirus SARS-CoV-2 being responsible for the COVID-19 pandemic) packaged within filament-like helical capsid. Such ribonucleocapsid is transported into spherical membrane envelope with incorporated spike glycoproteins. Two other examples concern the genomes of viruses with icosahedral capsids, satellite tobacco mosaic virus (STMV) and bacteriophage PHIX174. A part of the quasi-periodic motifs in these viral genomes was evolved due to weakly specific cooperative interaction between genomic ssRNA/ssDNA and nucleocapsid proteins. The symmetry of the capsids leads to the natural selection of specific quasi-periodic motifs in the related genomic sequences. Generally, TAMGI provides a convenient tool for the study of numerous molecular mechanisms with participation of both quasi-periodic motifs and complete repeats, the genome organization, contextual analysis of cis/trans regulatory elements, data mining, and correlations in the genomic sequences.

Evolving ribonucleocapsid assembly/packaging signals in the genomes of the human and animal coronaviruses: targeting, transmission and evolution

“…where α ϕ is the frequency of nucleotides of the type α retained under reshuffling (the detailed theory for TAMGI, including the derivation of Eq. ( 5), can be found in the paper by Chechetkin & Lobzin (2021)).…”

Genome-Wide Study of Colocalization between Genomic Stretches: A Method and Applications to the Regulation of Gene Expression

“…In particular, coarse-graining of various profiles (e.g., AT/GC content, expression profiles, protein binding profiles) results in a set of stretches within which the characteristics exceed some thresholds. Previously, it was shown that the coarse-grained profiles obtained by transitional automorphic mapping of the genome on itself (TAMGI) contain important information about functional regions in viral genomes [ 55 , 56 ]. The colocalization between stretch sets obtained by coarse-graining of profiles can also be treated by the method developed in our paper.…”