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Developmental gene regulatory network connections predicted by machine learning from gene expression data alone

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dc.contributor.authorZhang, Jingyien
dc.contributor.authorIbrahim, Farhanen
dc.contributor.authorNajmulski, Emilyen
dc.contributor.authorKatholos, Georgeen
dc.contributor.authorAltarawy, Doaaen
dc.contributor.authorHeath, Lenwood S.en
dc.contributor.authorTulin, Sarah L.en
dc.date.accessioned2022-08-31T13:02:40Zen
dc.date.available2022-08-31T13:02:40Zen
dc.date.issued2021-12-28en
dc.description.abstractGene regulatory network (GRN) inference can now take advantage of powerful machine learning algorithms to complement traditional experimental methods in building gene networks. However, the dynamical nature of embryonic development-representing the timedependent interactions between thousands of transcription factors, signaling molecules, and effector genes-is one of the most challenging arenas for GRN prediction. In this work, we show that successful GRN predictions for a developmental network from gene expression data alone can be obtained with the Priors Enriched Absent Knowledge (PEAK) network inference algorithm. PEAK is a noise-robust method that models gene expression dynamics via ordinary differential equations and selects the best network based on information-theoretic criteria coupled with the machine learning algorithm Elastic Net. We test our GRN prediction methodology using two gene expression datasets for the purple sea urchin, Stronglyocentrotus purpuratus, and cross-check our results against existing GRN models that have been constructed and validated by over 30 years of experimental results. Our results find a remarkably high degree of sensitivity in identifying known gene interactions in the network (maximum 81.58%). We also generate novel predictions for interactions that have not yet been described, which provide a resource for researchers to use to further complete the sea urchin GRN. Published ChIPseq data and spatial co-expression analysis further support a subset of the top novel predictions. We conclude that GRN predictions that match known gene interactions can be produced using gene expression data alone from developmental time series experiments.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0261926en
dc.identifier.issn1932-6203en
dc.identifier.issue12en
dc.identifier.othere0261926en
dc.identifier.pmid34962963en
dc.identifier.urihttp://hdl.handle.net/10919/111677en
dc.identifier.volume16en
dc.language.isoenen
dc.publisherPLOSen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectmessenger-rnasen
dc.subjectspecificationen
dc.subjectvisualizationen
dc.subjecttranscriptomeen
dc.subjectgenomeen
dc.titleDevelopmental gene regulatory network connections predicted by machine learning from gene expression data aloneen
dc.title.serialPLoS Oneen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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