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StaRTrEK:in silico estimation of RNA half-lives from genome-wide time-course experiments without transcriptional inhibition

BACKGROUND: Gene expression is the result of the balance between transcription and degradation. Recent experimental findings have shown fine and specific regulation of RNA degradation and the presence of various molecular machinery purposely devoted to this task, such as RNA binding proteins, non-co...

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Autores principales: Conte, Federica, Papa, Federico, Paci, Paola, Farina, Lorenzo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9123730/
https://www.ncbi.nlm.nih.gov/pubmed/35596139
http://dx.doi.org/10.1186/s12859-022-04730-x
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author Conte, Federica
Papa, Federico
Paci, Paola
Farina, Lorenzo
author_facet Conte, Federica
Papa, Federico
Paci, Paola
Farina, Lorenzo
author_sort Conte, Federica
collection PubMed
description BACKGROUND: Gene expression is the result of the balance between transcription and degradation. Recent experimental findings have shown fine and specific regulation of RNA degradation and the presence of various molecular machinery purposely devoted to this task, such as RNA binding proteins, non-coding RNAs, etc. A biological process can be studied by measuring time-courses of RNA abundance in response of internal and/or external stimuli, using recent technologies, such as the microarrays or the Next Generation Sequencing devices. Unfortunately, the picture provided by looking only at the transcriptome abundance may not gain insight into its dynamic regulation. By contrast, independent simultaneous measurement of RNA expression and half-lives could provide such valuable additional insight. A computational approach to the estimation of RNAs half-lives from RNA expression time profiles data, can be a low-cost alternative to its experimental measurement which may be also affected by various artifacts. RESULTS: Here we present a computational methodology, called StaRTrEK (STAbility Rates ThRough Expression Kinetics), able to estimate half-life values basing only on genome-wide gene expression time series without transcriptional inhibition. The StaRTrEK algorithm makes use of a simple first order kinetic model and of a [Formula: see text] -norm regularized least square optimization approach to find its parameter values. Estimates provided by StaRTrEK are validated using simulated data and three independent experimental datasets of two short (6 samples) and one long (48 samples) time-courses. CONCLUSIONS: We believe that our algorithm can be used as a fast valuable computational complement to time-course experimental gene expression studies by adding a relevant kinetic property, i.e. the RNA half-life, with a strong biological interpretation, thus providing a dynamic picture of what is going in a cell during the biological process under study. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12859-022-04730-x.
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spelling pubmed-91237302022-05-22 StaRTrEK:in silico estimation of RNA half-lives from genome-wide time-course experiments without transcriptional inhibition Conte, Federica Papa, Federico Paci, Paola Farina, Lorenzo BMC Bioinformatics Research BACKGROUND: Gene expression is the result of the balance between transcription and degradation. Recent experimental findings have shown fine and specific regulation of RNA degradation and the presence of various molecular machinery purposely devoted to this task, such as RNA binding proteins, non-coding RNAs, etc. A biological process can be studied by measuring time-courses of RNA abundance in response of internal and/or external stimuli, using recent technologies, such as the microarrays or the Next Generation Sequencing devices. Unfortunately, the picture provided by looking only at the transcriptome abundance may not gain insight into its dynamic regulation. By contrast, independent simultaneous measurement of RNA expression and half-lives could provide such valuable additional insight. A computational approach to the estimation of RNAs half-lives from RNA expression time profiles data, can be a low-cost alternative to its experimental measurement which may be also affected by various artifacts. RESULTS: Here we present a computational methodology, called StaRTrEK (STAbility Rates ThRough Expression Kinetics), able to estimate half-life values basing only on genome-wide gene expression time series without transcriptional inhibition. The StaRTrEK algorithm makes use of a simple first order kinetic model and of a [Formula: see text] -norm regularized least square optimization approach to find its parameter values. Estimates provided by StaRTrEK are validated using simulated data and three independent experimental datasets of two short (6 samples) and one long (48 samples) time-courses. CONCLUSIONS: We believe that our algorithm can be used as a fast valuable computational complement to time-course experimental gene expression studies by adding a relevant kinetic property, i.e. the RNA half-life, with a strong biological interpretation, thus providing a dynamic picture of what is going in a cell during the biological process under study. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12859-022-04730-x. BioMed Central 2022-05-20 /pmc/articles/PMC9123730/ /pubmed/35596139 http://dx.doi.org/10.1186/s12859-022-04730-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Conte, Federica
Papa, Federico
Paci, Paola
Farina, Lorenzo
StaRTrEK:in silico estimation of RNA half-lives from genome-wide time-course experiments without transcriptional inhibition
title StaRTrEK:in silico estimation of RNA half-lives from genome-wide time-course experiments without transcriptional inhibition
title_full StaRTrEK:in silico estimation of RNA half-lives from genome-wide time-course experiments without transcriptional inhibition
title_fullStr StaRTrEK:in silico estimation of RNA half-lives from genome-wide time-course experiments without transcriptional inhibition
title_full_unstemmed StaRTrEK:in silico estimation of RNA half-lives from genome-wide time-course experiments without transcriptional inhibition
title_short StaRTrEK:in silico estimation of RNA half-lives from genome-wide time-course experiments without transcriptional inhibition
title_sort startrek:in silico estimation of rna half-lives from genome-wide time-course experiments without transcriptional inhibition
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9123730/
https://www.ncbi.nlm.nih.gov/pubmed/35596139
http://dx.doi.org/10.1186/s12859-022-04730-x
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