Crinet: A computational tool to infer genome-wide competing endogenous RNA (ceRNA) interactions.

To understand driving biological factors for complex diseases like cancer, regulatory circuity of genes needs to be discovered. Recently, a new gene regulation mechanism called competing endogenous RNA (ceRNA) interactions has been discovered. Certain genes targeted by common microRNAs (miRNAs) &quo...

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Autores principales:	Ziynet Nesibe Kesimoglu, Serdar Bozdag
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/75aad5680b7f4a668c135b46a8e8122c
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spelling	oai:doaj.org-article:75aad5680b7f4a668c135b46a8e8122c2021-12-02T20:04:06ZCrinet: A computational tool to infer genome-wide competing endogenous RNA (ceRNA) interactions.1932-620310.1371/journal.pone.0251399https://doaj.org/article/75aad5680b7f4a668c135b46a8e8122c2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0251399https://doaj.org/toc/1932-6203To understand driving biological factors for complex diseases like cancer, regulatory circuity of genes needs to be discovered. Recently, a new gene regulation mechanism called competing endogenous RNA (ceRNA) interactions has been discovered. Certain genes targeted by common microRNAs (miRNAs) "compete" for these miRNAs, thereby regulate each other by making others free from miRNA regulation. Several computational tools have been published to infer ceRNA networks. In most existing tools, however, expression abundance sufficiency, collective regulation, and groupwise effect of ceRNAs are not considered. In this study, we developed a computational tool named Crinet to infer genome-wide ceRNA networks addressing critical drawbacks. Crinet considers all mRNAs, lncRNAs, and pseudogenes as potential ceRNAs and incorporates a network deconvolution method to exclude the spurious ceRNA pairs. We tested Crinet on breast cancer data in TCGA. Crinet inferred reproducible ceRNA interactions and groups, which were significantly enriched in the cancer-related genes and processes. We validated the selected miRNA-target interactions with the protein expression-based benchmarks and also evaluated the inferred ceRNA interactions predicting gene expression change in knockdown assays. The hub genes in the inferred ceRNA network included known suppressor/oncogene lncRNAs in breast cancer showing the importance of non-coding RNA's inclusion for ceRNA inference. Crinet-inferred ceRNA groups that were consistently involved in the immune system related processes could be important assets in the light of the studies confirming the relation between immunotherapy and cancer. The source code of Crinet is in R and available at https://github.com/bozdaglab/crinet.Ziynet Nesibe KesimogluSerdar BozdagPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 5, p e0251399 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ziynet Nesibe Kesimoglu Serdar Bozdag Crinet: A computational tool to infer genome-wide competing endogenous RNA (ceRNA) interactions.
description	To understand driving biological factors for complex diseases like cancer, regulatory circuity of genes needs to be discovered. Recently, a new gene regulation mechanism called competing endogenous RNA (ceRNA) interactions has been discovered. Certain genes targeted by common microRNAs (miRNAs) "compete" for these miRNAs, thereby regulate each other by making others free from miRNA regulation. Several computational tools have been published to infer ceRNA networks. In most existing tools, however, expression abundance sufficiency, collective regulation, and groupwise effect of ceRNAs are not considered. In this study, we developed a computational tool named Crinet to infer genome-wide ceRNA networks addressing critical drawbacks. Crinet considers all mRNAs, lncRNAs, and pseudogenes as potential ceRNAs and incorporates a network deconvolution method to exclude the spurious ceRNA pairs. We tested Crinet on breast cancer data in TCGA. Crinet inferred reproducible ceRNA interactions and groups, which were significantly enriched in the cancer-related genes and processes. We validated the selected miRNA-target interactions with the protein expression-based benchmarks and also evaluated the inferred ceRNA interactions predicting gene expression change in knockdown assays. The hub genes in the inferred ceRNA network included known suppressor/oncogene lncRNAs in breast cancer showing the importance of non-coding RNA's inclusion for ceRNA inference. Crinet-inferred ceRNA groups that were consistently involved in the immune system related processes could be important assets in the light of the studies confirming the relation between immunotherapy and cancer. The source code of Crinet is in R and available at https://github.com/bozdaglab/crinet.
format	article
author	Ziynet Nesibe Kesimoglu Serdar Bozdag
author_facet	Ziynet Nesibe Kesimoglu Serdar Bozdag
author_sort	Ziynet Nesibe Kesimoglu
title	Crinet: A computational tool to infer genome-wide competing endogenous RNA (ceRNA) interactions.
title_short	Crinet: A computational tool to infer genome-wide competing endogenous RNA (ceRNA) interactions.
title_full	Crinet: A computational tool to infer genome-wide competing endogenous RNA (ceRNA) interactions.
title_fullStr	Crinet: A computational tool to infer genome-wide competing endogenous RNA (ceRNA) interactions.
title_full_unstemmed	Crinet: A computational tool to infer genome-wide competing endogenous RNA (ceRNA) interactions.
title_sort	crinet: a computational tool to infer genome-wide competing endogenous rna (cerna) interactions.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/75aad5680b7f4a668c135b46a8e8122c
work_keys_str_mv	AT ziynetnesibekesimoglu crinetacomputationaltooltoinfergenomewidecompetingendogenousrnacernainteractions AT serdarbozdag crinetacomputationaltooltoinfergenomewidecompetingendogenousrnacernainteractions
_version_	1718375609663488000

Crinet: A computational tool to infer genome-wide competing endogenous RNA (ceRNA) interactions.

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