Comparative Analysis of RNA-Chromatin Interactome Data: Resolution, Completeness, and Specificity

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Grigory K. Ryabykh^1,2,a*, Arina I. Nikolskaya^1,2, Lidia D. Garkul¹, and Andrey A. Mironov^1,2

¹Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119234 Moscow, Russia

²Vavilov Institute of General Genetics, Russian Academy of Sciences, 119991 Moscow, Russia

^* To whom correspondence should be addressed.

Received: July 3, 2025; Revised: October 25, 2025; Accepted: October 28, 2025

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Two types of experiments are used to study RNA-chromatin interactions: the interactome search for individual RNAs (“one-to-all” or OTA) and genome-wide contact mapping for all RNAs (“all-to-all” or ATA). Comparative analysis of ATA and OTA data revealed fundamental differences in resolution, completeness, and specificity. OTA data exhibit high resolution (~1000 bp) and reproducibility (>90%), serving as a “gold standard”. ATA data, however, have lower resolution (~5000 bp), and their reproducibility (<10%) is critically dependent on the protocol, with two-step fixation using disuccinimidyl glutarate and formaldehyde (GRID-seq) showing a clear advantage over formaldehyde alone. The introduced “chromatin potential” metric and BaRDIC peak filtering effectively isolate the specific signal. This study proposes a strategy for reliable interactome analysis: combining RNA selection based on chromatin potential with the use of concordant contacts from peaks.

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KEY WORDS: RNA-chromatin interactome, non-coding RNAs, RNA-Chrom database, RNA-chromatin interactome data concordance

DOI: 10.1134/S0006297925601923

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