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Numerous methods exist for profiling mRNA transcript levels and identifying protein-DNA binding interactions at the genome-wide scale. These enable researchers to determine the structure and output of transcriptional regulatory networks, but uncovering the complete structure and regulatory logic of GRNs remains a challenge. The field of GRN inference aims to meet this challenge using computational modeling to derive the structure and logic of GRNs from experimental data and to encode this knowledge in Boolean networks, Bayesian networks, ordinary differential equation (ODE) models, or other modeling frameworks. However, most existing models do not incorporate dynamic transcriptional data since it has historically been less widely available in comparison to \u201cstatic\u201d transcriptional data. We report the development of an evolutionary algorithm-based ODE modeling approach (named EA) that integrates kinetic transcription data and the theory of attractor matching to infer GRN architecture and regulatory logic. Our method outperformed six leading GRN inference methods, none of which incorporate kinetic transcriptional data, in predicting regulatory connections among TFs when applied to a small-scale engineered synthetic GRN in\n                    <jats:italic>Saccharomyces cerevisiae<\/jats:italic>\n                    . Moreover, we demonstrate the potential of our method to predict unknown transcriptional profiles that would be produced upon genetic perturbation of the GRN governing a two-state cellular phenotypic switch in\n                    <jats:italic>Candida albicans<\/jats:italic>\n                    . We established an iterative refinement strategy to facilitate candidate selection for experimentation; the experimental results in turn provide validation or improvement for the model. In this way, our GRN inference approach can expedite the development of a sophisticated mathematical model that can accurately describe the structure and dynamics of the\n                    <jats:italic>in vivo<\/jats:italic>\n                    GRN.\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1010991","type":"journal-article","created":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T13:53:52Z","timestamp":1692712432000},"page":"e1010991","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Inferring gene regulatory networks using transcriptional profiles as dynamical attractors"],"prefix":"10.1371","volume":"19","author":[{"given":"Ruihao","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jordan C.","family":"Rozum","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morgan M.","family":"Quail","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad N.","family":"Qasim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzanne S.","family":"Sindi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0799-6499","authenticated-orcid":true,"given":"Clarissa J.","family":"Nobile","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R\u00e9ka","family":"Albert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9351-7150","authenticated-orcid":true,"given":"Aaron D.","family":"Hernday","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,8,22]]},"reference":[{"issue":"4","key":"pcbi.1010991.ref001","doi-asserted-by":"crossref","first-page":"444","DOI":"10.15388\/NA.18.4.13972","article-title":"A survey of models for inference of gene regulatory networks","volume":"18","author":"B Ristevski","year":"2013","journal-title":"Nonlinear Analysis: Modelling and Control"},{"issue":"2","key":"pcbi.1010991.ref002","doi-asserted-by":"crossref","first-page":"792","DOI":"10.15252\/msb.20145549","article-title":"Cell dynamics and gene expression control in tissue homeostasis and development","volume":"11","author":"P Ru\u00e9","year":"2015","journal-title":"Molecular systems biology"},{"issue":"1","key":"pcbi.1010991.ref003","first-page":"1","article-title":"Attractor concepts to evaluate the transcriptome-wide Dynamics Guiding Anaerobic to Aerobic State transition in Escherichia coli","volume":"10","author":"TT Bui","year":"2020","journal-title":"Scientific reports"},{"issue":"5762","key":"pcbi.1010991.ref004","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1126\/science.1113832","article-title":"Gene regulatory networks and the evolution of animal body plans","volume":"311","author":"EH Davidson","year":"2006","journal-title":"Science"},{"issue":"5","key":"pcbi.1010991.ref005","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.stem.2009.04.011","article-title":"Stem cell states, fates, and the rules of attraction","volume":"4","author":"T Enver","year":"2009","journal-title":"Cell stem cell"},{"issue":"4","key":"pcbi.1010991.ref006","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/j.jtbi.2003.12.017","article-title":"A proposal for using the ensemble approach to understand genetic regulatory networks","volume":"230","author":"S Kauffman","year":"2004","journal-title":"Journal of theoretical biology"},{"issue":"5","key":"pcbi.1010991.ref007","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/gm340","article-title":"Gene regulatory network inference: evaluation and application to ovarian cancer allows the prioritization of drug targets","volume":"4","author":"PB Madhamshettiwar","year":"2012","journal-title":"Genome Medicine"},{"issue":"1","key":"pcbi.1010991.ref008","doi-asserted-by":"crossref","first-page":"38","DOI":"10.2174\/1389202919666181107122005","article-title":"Prostate cancer gene regulatory network inferred from RNA-Seq data","volume":"20","author":"D Moore","year":"2019","journal-title":"Current genomics"},{"key":"pcbi.1010991.ref009","doi-asserted-by":"crossref","first-page":"535","DOI":"10.3389\/fgene.2019.00535","article-title":"Inferring interaction networks from multi-comics data-a review","volume":"10","author":"JS Hawe","year":"2019","journal-title":"Frontiers in genetics"},{"key":"pcbi.1010991.ref010","doi-asserted-by":"crossref","unstructured":"Natale JL, Hofmann D, Hern\u00e1ndez DG, Nemenman I. 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