COMPARATIVE ANALYSIS OF THE RNA-CHROMATIN INTERACTOME DATA: RESOLUTION, COMPLETENESS, AND SPECIFICITY OF DATA

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Abstract

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

About the authors

G. K Ryabykh

Lomonosov Moscow State University; Vavilov Institute of General Genetics, Russian Academy of Sciences

Email: ryabykhgrigory@gmail.com
119234 Moscow, Russia; 119991 Moscow, Russia

A. I Nikolskaya

Lomonosov Moscow State University; Vavilov Institute of General Genetics, Russian Academy of Sciences

119234 Moscow, Russia; 119991 Moscow, Russia

L. D Garkul

Lomonosov Moscow State University

119234 Moscow, Russia

A. A Mironov

Lomonosov Moscow State University; Vavilov Institute of General Genetics, Russian Academy of Sciences

119234 Moscow, Russia; 119991 Moscow, Russia

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