Experiment level curation of transcriptional regulatory interactions in neurodevelopment.

To facilitate the development of large-scale transcriptional regulatory networks (TRNs) that may enable in-silico analyses of disease mechanisms, a reliable catalogue of experimentally verified direct transcriptional regulatory interactions (DTRIs) is needed for training and validation. There has be...

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Autores principales:	Eric Ching-Pan Chu, Alexander Morin, Tak Hou Calvin Chang, Tue Nguyen, Yi-Cheng Tsai, Aman Sharma, Chao Chun Liu, Paul Pavlidis
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/3b7a9cfb39774e8ca60d5c3d0021ab32
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spelling	oai:doaj.org-article:3b7a9cfb39774e8ca60d5c3d0021ab322021-12-02T19:57:29ZExperiment level curation of transcriptional regulatory interactions in neurodevelopment.1553-734X1553-735810.1371/journal.pcbi.1009484https://doaj.org/article/3b7a9cfb39774e8ca60d5c3d0021ab322021-10-01T00:00:00Zhttps://doi.org/10.1371/journal.pcbi.1009484https://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358To facilitate the development of large-scale transcriptional regulatory networks (TRNs) that may enable in-silico analyses of disease mechanisms, a reliable catalogue of experimentally verified direct transcriptional regulatory interactions (DTRIs) is needed for training and validation. There has been a long history of using low-throughput experiments to validate single DTRIs. Therefore, we reason that a reliable set of DTRIs could be produced by curating the published literature for such evidence. In our survey of previous curation efforts, we identified the lack of details about the quantity and the types of experimental evidence to be a major gap, despite the theoretical importance of such details for the identification of bona fide DTRIs. We developed a curation protocol to inspect the published literature for support of DTRIs at the experiment level, focusing on genes important to the development of the mammalian nervous system. We sought to record three types of low-throughput experiments: Transcription factor (TF) perturbation, TF-DNA binding, and TF-reporter assays. Using this protocol, we examined a total of 1,310 papers to assemble a collection of 1,499 unique DTRIs, involving 251 TFs and 825 target genes, many of which were not reported in any other DTRI resource. The majority of DTRIs (965; 64%) were supported by two or more types of experimental evidence and 27% were supported by all three. Of the DTRIs with all three types of evidence, 170 had been tested using primary tissues or cells and 44 had been tested directly in the central nervous system. We used our resource to document research biases among reports towards a small number of well-studied TFs. To demonstrate a use case for this resource, we compared our curation to a previously published high-throughput perturbation screen and found significant enrichment of the curated targets among genes differentially expressed in the developing brain in response to Pax6 deletion. This study demonstrates a proof-of-concept for the assembly of a high resolution DTRI resource to support the development of large-scale TRNs.Eric Ching-Pan ChuAlexander MorinTak Hou Calvin ChangTue NguyenYi-Cheng TsaiAman SharmaChao Chun LiuPaul PavlidisPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 17, Iss 10, p e1009484 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Eric Ching-Pan Chu Alexander Morin Tak Hou Calvin Chang Tue Nguyen Yi-Cheng Tsai Aman Sharma Chao Chun Liu Paul Pavlidis Experiment level curation of transcriptional regulatory interactions in neurodevelopment.
description	To facilitate the development of large-scale transcriptional regulatory networks (TRNs) that may enable in-silico analyses of disease mechanisms, a reliable catalogue of experimentally verified direct transcriptional regulatory interactions (DTRIs) is needed for training and validation. There has been a long history of using low-throughput experiments to validate single DTRIs. Therefore, we reason that a reliable set of DTRIs could be produced by curating the published literature for such evidence. In our survey of previous curation efforts, we identified the lack of details about the quantity and the types of experimental evidence to be a major gap, despite the theoretical importance of such details for the identification of bona fide DTRIs. We developed a curation protocol to inspect the published literature for support of DTRIs at the experiment level, focusing on genes important to the development of the mammalian nervous system. We sought to record three types of low-throughput experiments: Transcription factor (TF) perturbation, TF-DNA binding, and TF-reporter assays. Using this protocol, we examined a total of 1,310 papers to assemble a collection of 1,499 unique DTRIs, involving 251 TFs and 825 target genes, many of which were not reported in any other DTRI resource. The majority of DTRIs (965; 64%) were supported by two or more types of experimental evidence and 27% were supported by all three. Of the DTRIs with all three types of evidence, 170 had been tested using primary tissues or cells and 44 had been tested directly in the central nervous system. We used our resource to document research biases among reports towards a small number of well-studied TFs. To demonstrate a use case for this resource, we compared our curation to a previously published high-throughput perturbation screen and found significant enrichment of the curated targets among genes differentially expressed in the developing brain in response to Pax6 deletion. This study demonstrates a proof-of-concept for the assembly of a high resolution DTRI resource to support the development of large-scale TRNs.
format	article
author	Eric Ching-Pan Chu Alexander Morin Tak Hou Calvin Chang Tue Nguyen Yi-Cheng Tsai Aman Sharma Chao Chun Liu Paul Pavlidis
author_facet	Eric Ching-Pan Chu Alexander Morin Tak Hou Calvin Chang Tue Nguyen Yi-Cheng Tsai Aman Sharma Chao Chun Liu Paul Pavlidis
author_sort	Eric Ching-Pan Chu
title	Experiment level curation of transcriptional regulatory interactions in neurodevelopment.
title_short	Experiment level curation of transcriptional regulatory interactions in neurodevelopment.
title_full	Experiment level curation of transcriptional regulatory interactions in neurodevelopment.
title_fullStr	Experiment level curation of transcriptional regulatory interactions in neurodevelopment.
title_full_unstemmed	Experiment level curation of transcriptional regulatory interactions in neurodevelopment.
title_sort	experiment level curation of transcriptional regulatory interactions in neurodevelopment.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/3b7a9cfb39774e8ca60d5c3d0021ab32
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Experiment level curation of transcriptional regulatory interactions in neurodevelopment.

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