Comprehensive analysis of RNA–chromatin, RNA–, and DNA–protein interactions

Комплексный анализ взаимодействий РНК–хроматин, РНК– и ДНК–белок
Daniil A. Khlebnikov, Arina I. Nikolskaya, Anastasia A. Zharikova, Andrey A. Mironov
2025-01-07

RADICL-seq NPM (negative control)RNA–chromatin interactomeRed-ChIP (positive control)pairwise RNA–protein–DNA interactionstriad interaction (RNA-protein-DNA locus)
RNA-chromatin interactome data are considered to be one of the noisiest types of data in biology. This is due to protein-coding RNA contacts and nonspecific interactions between RNA and chromatin caused by protocol specifics. Therefore, finding regulatory interactions between certain transcripts and genome loci requires a wide range of filtering techniques to obtain significant results. Using data on pairwise interactions between these molecules, we propose a concept of triad interaction involving RNA, protein, and a DNA locus. The constructed triads show significantly less noise contacts and are more significant when compared to a background model for generating pairwise interactions. RNA-chromatin contacts data can be used to validate the proposed triad object as positive (Red-ChIP experiment) or negative (RADICL-seq NPM) controls. Our approach also filters RNA-chromatin contacts in chromatin regions associated with protein functions based on ChromHMM annotation.
1
Constructed triads exhibit significantly less noisy contacts compared to raw pairwise RNA–chromatin interaction data.
2
RNA–chromatin contact datasets (Red-ChIP and RADICL-seq NPM) can validate triads as positive or negative controls respectively.
3
RNA–protein–DNA triads (RNA, protein, and DNA locus) are proposed as a concept derived from pairwise interaction data.
4
The method filters RNA–chromatin contacts by restricting to chromatin regions associated with protein functions using ChromHMM annotation.
5
Triads are more significant than pairwise interactions when compared to a background model for generating pairwise interactions.

Triad interaction object composed of RNA, protein, and a DNA locus (RNA–protein–DNA triad)

Reduction of noise and identification/validation of regulatory RNA–chromatin interactions by constructing and analyzing RNA–protein–DNA triads, including comparison to background pairwise models and filtering using experimental controls and ChromHMM-based chromatin annotations

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2025-01-07
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Authors
Daniil A. Khlebnikov
Arina I. Nikolskaya
Anastasia A. Zharikova
Andrey A. Mironov
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