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Thiel, D.* ; Conrad, N.D.* ; Ntini, E.* ; Peschutter, R.X.* ; Siebert, H.* ; Marsico, A.

Identifying lncRNA-mediated regulatory modules via ChIA-PET network analysis.

BMC Bioinformatics 20:292 (2019)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Background: Although several studies have provided insights into the role of long non-coding RNAs (lncRNAs), the majority of them have unknown function. Recent evidence has shown the importance of both lncRNAs and chromatin interactions in transcriptional regulation. Although network-based methods, mainly exploiting gene-lncRNA co-expression, have been applied to characterize lncRNA of unknown function by means of 'guilt-by-association', no strategy exists so far which identifies mRNA-lncRNA functional modules based on the 3D chromatin interaction graph. Results: To better understand the function of chromatin interactions in the context of lncRNA-mediated gene regulation, we have developed a multi-step graph analysis approach to examine the RNA polymerase II ChIA-PET chromatin interaction network in the K562 human cell line. We have annotated the network with gene and lncRNA coordinates, and chromatin states from the ENCODE project. We used centrality measures, as well as an adaptation of our previously developed Markov State Models (MSM) clustering method, to gain a better understanding of lncRNAs in transcriptional regulation. The novelty of our approach resides in the detection of fuzzy regulatory modules based on network properties and their optimization based on co-expression analysis between genes and gene-lncRNA pairs. This results in our method returning more bona fide regulatory modules than other state-of-the art approaches for clustering on graphs. Conclusions: Interestingly, we find that lncRNA network hubs tend to be significantly enriched in evolutionary conserved lncRNAs and enhancer-like functions. We validated regulatory functions for well known lncRNAs, such as MALAT1 and the enhancer-like lncRNA FALEC. In addition, by investigating the modular structure of bigger components we mine putative regulatory functions for uncharacterized lncRNAs.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Chia-pet ; Gene Regulation ; Lncrna ; Modules ; Network Analysis; Long Noncoding Rnas; Chromatin-state; Cell; Transcription; Expression; Prediction; Enhancers; Sequences; Genomics; Lincrnas
ISSN (print) / ISBN 1471-2105
e-ISSN 1471-2105
Zeitschrift BMC Bioinformatics
Quellenangaben Band: 20, Heft: 1, Seiten: , Artikelnummer: 292 Supplement: ,
Verlag BioMed Central
Verlagsort Campus, 4 Crinan St, London N1 9xw, England
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Computational Biology (ICB)