{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:38:16Z","timestamp":1776127096195,"version":"3.50.1"},"reference-count":48,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2021,12,3]],"date-time":"2021-12-03T00:00:00Z","timestamp":1638489600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research, Development and Innovation Office of Hungary","award":["K_20 134489"],"award-info":[{"award-number":["K_20 134489"]}]},{"name":"Thematic Excellence Programme","award":["TKP2020-NKA-11"],"award-info":[{"award-number":["TKP2020-NKA-11"]}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Cells can maintain their homeostasis in a noisy environment since their signaling pathways can filter out noise somehow. Several network motifs have been proposed for biological noise filtering and, among these, feed-forward loops have received special attention. Specific feed-forward loops show noise reducing capabilities, but we notice that this feature comes together with a reduced signal transducing performance. In posttranslational signaling pathways feed-forward loops do not function in isolation, rather they are coupled with other motifs to serve a more complex function. Feed-forward loops are often coupled to other feed-forward loops, which could affect their noise-reducing capabilities. Here we systematically study all feed-forward loop motifs and all their pairwise coupled systems with activation-inactivation kinetics to identify which networks are capable of good noise reduction, while keeping their signal transducing performance. Our analysis shows that coupled feed-forward loops can provide better noise reduction and, at the same time, can increase the signal transduction of the system. The coupling of two coherent 1 or one coherent 1 and one incoherent 4 feed-forward loops can give the best performance in both of these measures.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1009622","type":"journal-article","created":{"date-parts":[[2021,12,3]],"date-time":"2021-12-03T18:22:13Z","timestamp":1638555733000},"page":"e1009622","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Systematic analysis of noise reduction properties of coupled and isolated feed-forward loops"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6643-3085","authenticated-orcid":true,"given":"Suchana","family":"Chakravarty","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2919-5601","authenticated-orcid":true,"given":"Attila","family":"Csik\u00e1sz-Nagy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,12,3]]},"reference":[{"key":"pcbi.1009622.ref001","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1038\/nature08781","article-title":"Variability in gene expression underlies incomplete penetrance","volume":"463","author":"A Raj","year":"2010","journal-title":"Nature"},{"key":"pcbi.1009622.ref002","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fphy.2018.00036","article-title":"Experimental and Modeling Approaches for Understanding the Effect of Gene Expression Noise in Biological Development","volume":"6","author":"DM Holloway","year":"2018","journal-title":"Front Phys"},{"key":"pcbi.1009622.ref003","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1371\/journal.pbio.0020137","article-title":"Noise minimization in eukaryotic gene expression","volume":"2","author":"HB Fraser","year":"2004","journal-title":"PLoS Biol"},{"key":"pcbi.1009622.ref004","doi-asserted-by":"crossref","first-page":"12795","DOI":"10.1073\/pnas.162041399","article-title":"Intrinsic and extrinsic contributions to stochasticity in gene expression","volume":"99","author":"PS Swain","year":"2002","journal-title":"Proc Natl Acad Sci"},{"key":"pcbi.1009622.ref005","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1038\/ng1616","article-title":"Contributions of low molecule number and chromosomal positioning to stochastic gene expression","volume":"37","author":"A Becskei","year":"2005","journal-title":"Nat Genet"},{"key":"pcbi.1009622.ref006","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-018-35927-x","article-title":"Intrinsic and extrinsic noise of gene expression in lineage trees","volume":"9","author":"P Thomas","year":"2019","journal-title":"Sci Rep"},{"key":"pcbi.1009622.ref007","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1126\/science.1144331","article-title":"Effects of Molecular Memory and Bursting on Fluctuations in Gene Expression","volume":"319","author":"JM Pedraza","year":"2008","journal-title":"Science (80-)."},{"key":"pcbi.1009622.ref008","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.plrev.2005.03.003","article-title":"Models of stochastic gene expression","volume":"2","author":"J. 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