Stochastic dynamics of type-I interferon responses
Interferon (IFN) activates the transcription of several hundred of IFN stimulated genes (ISGs) that constitute a highly effective antiviral defense program. Cell-to-cell variability in the induction of ISGs is well documented, but its source and effects are not completely understood. The molecular m...
Gespeichert in:
| Hauptverfasser: | , , , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
October 21, 2022
|
| Ausgabe: | Version 2 |
| In: |
PLoS Computational Biology
Year: 2022, Jahrgang: 18, Heft: 10, Pages: 1-24 |
| ISSN: | 1553-7358 |
| DOI: | 10.1371/journal.pcbi.1010623 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1371/journal.pcbi.1010623 Verlag, lizenzpflichtig, Volltext: https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1010623 
|
| Verfasserangaben: | Benjamin D. Maier, Luis U. Aguilera, Sven Sahle, Pascal Mutz, Priyata Kalra, Christopher Dächert, Ralf Bartenschlager, Marco Binder, Ursula Kummer |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1842947559 | ||
| 003 | DE-627 | ||
| 005 | 20230706224721.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 230417s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1371/journal.pcbi.1010623 |2 doi | |
| 035 | |a (DE-627)1842947559 | ||
| 035 | |a (DE-599)KXP1842947559 | ||
| 035 | |a (OCoLC)1389534004 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 32 |2 sdnb | ||
| 100 | 1 | |a Maier, Benjamin D. |e VerfasserIn |0 (DE-588)1286454948 |0 (DE-627)1842948466 |4 aut | |
| 245 | 1 | 0 | |a Stochastic dynamics of type-I interferon responses |c Benjamin D. Maier, Luis U. Aguilera, Sven Sahle, Pascal Mutz, Priyata Kalra, Christopher Dächert, Ralf Bartenschlager, Marco Binder, Ursula Kummer |
| 250 | |a Version 2 | ||
| 264 | 1 | |c October 21, 2022 | |
| 300 | |a 24 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 17.04.2023 | ||
| 520 | |a Interferon (IFN) activates the transcription of several hundred of IFN stimulated genes (ISGs) that constitute a highly effective antiviral defense program. Cell-to-cell variability in the induction of ISGs is well documented, but its source and effects are not completely understood. The molecular mechanisms behind this heterogeneity have been related to randomness in molecular events taking place during the JAK-STAT signaling pathway. Here, we study the sources of variability in the induction of the IFN-alpha response by using MxA and IFIT1 activation as read-out. To this end, we integrate time-resolved flow cytometry data and stochastic modeling of the JAK-STAT signaling pathway. The complexity of the IFN response was matched by fitting probability distributions to time-course flow cytometry snapshots. Both, experimental data and simulations confirmed that the MxA and IFIT1 induction circuits generate graded responses rather than all-or-none responses. Subsequently, we quantify the size of the intrinsic variability at different steps in the pathway. We found that stochastic effects are transiently strong during the ligand-receptor activation steps and the formation of the ISGF3 complex, but negligible for the final induction of the studied ISGs. We conclude that the JAK-STAT signaling pathway is a robust biological circuit that efficiently transmits information under stochastic environments. | ||
| 650 | 4 | |a Biochemical simulations | |
| 650 | 4 | |a Flow cytometry | |
| 650 | 4 | |a Interferons | |
| 650 | 4 | |a JAK-STAT signaling cascade | |
| 650 | 4 | |a Mathematical models | |
| 650 | 4 | |a Phosphorylation | |
| 650 | 4 | |a STAT signaling | |
| 650 | 4 | |a Transcription factors | |
| 700 | 1 | |a Aguilera, Luis U. |e VerfasserIn |0 (DE-588)1126593206 |0 (DE-627)881150274 |0 (DE-576)484583832 |4 aut | |
| 700 | 1 | |a Sahle, Sven |e VerfasserIn |0 (DE-588)1099116783 |0 (DE-627)85782452X |0 (DE-576)46921466X |4 aut | |
| 700 | 1 | |a Mutz, Pascal |e VerfasserIn |0 (DE-588)1156698383 |0 (DE-627)1019536195 |0 (DE-576)502385936 |4 aut | |
| 700 | 1 | |a Kalra, Priyata |e VerfasserIn |0 (DE-588)1181381096 |0 (DE-627)1662669690 |4 aut | |
| 700 | 1 | |a Dächert, Christopher |d 1989- |e VerfasserIn |0 (DE-588)1207113131 |0 (DE-627)1693370255 |4 aut | |
| 700 | 1 | |a Bartenschlager, Ralf |d 1958- |e VerfasserIn |0 (DE-588)1058097989 |0 (DE-627)796390509 |0 (DE-576)168706067 |4 aut | |
| 700 | 1 | |a Binder, Marco |e VerfasserIn |0 (DE-588)13571379X |0 (DE-627)69371171X |0 (DE-576)300603509 |4 aut | |
| 700 | 1 | |a Kummer, Ursula |d 1967- |e VerfasserIn |0 (DE-588)115411682 |0 (DE-627)691297975 |0 (DE-576)176480897 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |a Public Library of Science |t PLoS Computational Biology |d San Francisco, Calif. : Public Library of Science, 2005 |g 18(2022), 10, Artikel-ID e1010623, Seite 1-24 |h Online-Ressource |w (DE-627)491436017 |w (DE-600)2193340-6 |w (DE-576)273890492 |x 1553-7358 |7 nnas |
| 773 | 1 | 8 | |g volume:18 |g year:2022 |g number:10 |g elocationid:e1010623 |g pages:1-24 |g extent:24 |a Stochastic dynamics of type-I interferon responses |
| 856 | 4 | 0 | |u https://doi.org/10.1371/journal.pcbi.1010623 |x Verlag |x Resolving-System |z lizenzpflichtig |3 Volltext |
| 856 | 4 | 0 | |u https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1010623 |x Verlag |z lizenzpflichtig |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20230417 | ||
| 993 | |a Article | ||
| 994 | |a 2022 | ||
| 998 | |g 115411682 |a Kummer, Ursula |m 115411682:Kummer, Ursula |d 700000 |d 721000 |e 700000PK115411682 |e 721000PK115411682 |k 0/700000/ |k 1/700000/721000/ |p 9 |y j | ||
| 998 | |g 13571379X |a Binder, Marco |m 13571379X:Binder, Marco |d 140000 |e 140000PB13571379X |k 0/140000/ |p 8 | ||
| 998 | |g 1058097989 |a Bartenschlager, Ralf |m 1058097989:Bartenschlager, Ralf |d 910000 |d 911700 |e 910000PB1058097989 |e 911700PB1058097989 |k 0/910000/ |k 1/910000/911700/ |p 7 | ||
| 998 | |g 1181381096 |a Kalra, Priyata |m 1181381096:Kalra, Priyata |d 140000 |e 140000PK1181381096 |k 0/140000/ |p 5 | ||
| 998 | |g 1156698383 |a Mutz, Pascal |m 1156698383:Mutz, Pascal |d 140000 |e 140000PM1156698383 |k 0/140000/ |p 4 | ||
| 998 | |g 1099116783 |a Sahle, Sven |m 1099116783:Sahle, Sven |d 700000 |d 721000 |e 700000PS1099116783 |e 721000PS1099116783 |k 0/700000/ |k 1/700000/721000/ |p 3 | ||
| 999 | |a KXP-PPN1842947559 |e 4309552587 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"note":["Gesehen am 17.04.2023"],"origin":[{"dateIssuedDisp":"October 21, 2022","edition":"Version 2","dateIssuedKey":"2022"}],"relHost":[{"recId":"491436017","origin":[{"publisherPlace":"San Francisco, Calif.","dateIssuedKey":"2005","dateIssuedDisp":"2005-","publisher":"Public Library of Science"}],"note":["Gesehen am 23. November 2020"],"pubHistory":["1.2005 -"],"id":{"zdb":["2193340-6"],"eki":["491436017"],"issn":["1553-7358"]},"name":{"displayForm":["publ. by the Public Library of Science (PLoS) in association with the International Society for Computational Biology (ISCB)"]},"language":["eng"],"corporate":[{"display":"Public Library of Science","role":"aut"}],"title":[{"title":"PLoS Computational Biology","subtitle":"a new community journal","title_sort":"PLoS Computational Biology"}],"part":{"year":"2022","pages":"1-24","text":"18(2022), 10, Artikel-ID e1010623, Seite 1-24","volume":"18","extent":"24","issue":"10"},"disp":"Public Library of SciencePLoS Computational Biology","physDesc":[{"extent":"Online-Ressource"}],"type":{"media":"Online-Ressource","bibl":"periodical"}}],"recId":"1842947559","language":["eng"],"name":{"displayForm":["Benjamin D. Maier, Luis U. Aguilera, Sven Sahle, Pascal Mutz, Priyata Kalra, Christopher Dächert, Ralf Bartenschlager, Marco Binder, Ursula Kummer"]},"type":{"bibl":"article-journal","media":"Online-Ressource"},"physDesc":[{"extent":"24 S."}],"id":{"doi":["10.1371/journal.pcbi.1010623"],"eki":["1842947559"]},"person":[{"family":"Maier","role":"aut","display":"Maier, Benjamin D.","given":"Benjamin D."},{"family":"Aguilera","display":"Aguilera, Luis U.","given":"Luis U.","role":"aut"},{"display":"Sahle, Sven","given":"Sven","role":"aut","family":"Sahle"},{"role":"aut","given":"Pascal","display":"Mutz, Pascal","family":"Mutz"},{"family":"Kalra","role":"aut","display":"Kalra, Priyata","given":"Priyata"},{"role":"aut","display":"Dächert, Christopher","given":"Christopher","family":"Dächert"},{"family":"Bartenschlager","display":"Bartenschlager, Ralf","given":"Ralf","role":"aut"},{"given":"Marco","display":"Binder, Marco","role":"aut","family":"Binder"},{"family":"Kummer","role":"aut","display":"Kummer, Ursula","given":"Ursula"}],"title":[{"title_sort":"Stochastic dynamics of type-I interferon responses","title":"Stochastic dynamics of type-I interferon responses"}]} | ||
| SRT | |a MAIERBENJASTOCHASTIC2120 | ||