Unraveling the palindromic and nonpalindromic motifs of retroviral integration site sequences by statistical mixture models

0576660 - ÚMG 2024 RIV US eng J - Journal Article
Miklík, Dalibor - Grim, Jiří - Elleder, Daniel - Hejnar, Jiří
Unraveling the palindromic and nonpalindromic motifs of retroviral integration site sequences by statistical mixture models.
Genome Research. Roč. 33, č. 8 (2023), s. 1395-1408. ISSN 1088-9051. E-ISSN 1549-5469
R&D Projects: GA MŠMT(CZ) LX22NPO5103; GA ČR(CZ) GA19-23407S
Institutional support: RVO:67985556 ; RVO:68378050
Keywords : IMMUNODEFICIENCY-VIRUS TYPE-1 * HIV-1 INTEGRATION * HUMAN GENOME
OECD category: Biochemistry and molecular biology; Computer sciences, information science, bioinformathics (hardware development to be 2.2, social aspect to be 5.8) (UTIA-B)
Impact factor: 7, year: 2022
Method of publishing: Open access
https://genome.cshlp.org/content/33/8/1395

A weak palindromic nucleotide motif is the hallmark of retroviral integration site alignments. Given that the majority of target sequences are not palindromic, the current model explains the symmetry by an overlap of the nonpalindromic motif present on one of the half-sites of the sequences. Here, we show that the implementation of multicomponent mixture models allows for different interpretations consistent with the existence of both palindromic and nonpalindromic submotifs in the sets of integration site sequences. We further show that the weak palindromic motifs result from freely combined site-specific submotifs restricted to only a few positions proximal to the site of integration. The submotifs are formed by either palindrome-forming nucleotide preference or nucleotide exclusion. Using the mixture models, we also identify HIV-1-favored palindromic sequences in Alu repeats serving as local hotspots for integration. The application of the novel statistical approach provides deeper insight into the selection of retroviral integration sites and may prove to be a valuable tool in the analysis of any type of DNA motifs.
Permanent Link: https://hdl.handle.net/11104/0346204