Robustness and evolvability of the human signaling network
Biological systems are known to be both robust and evolvable to internal and external perturbations, but what causes these apparently contradictory properties? We used Boolean network modeling and attractor landscape analysis to investigate the evolvability and robustness of the human signaling netw...
Saved in:
Published in | PLoS computational biology Vol. 10; no. 7; p. e1003763 |
---|---|
Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Public Library of Science
01.07.2014
Public Library of Science (PLoS) |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Abstract | Biological systems are known to be both robust and evolvable to internal and external perturbations, but what causes these apparently contradictory properties? We used Boolean network modeling and attractor landscape analysis to investigate the evolvability and robustness of the human signaling network. Our results show that the human signaling network can be divided into an evolvable core where perturbations change the attractor landscape in state space, and a robust neighbor where perturbations have no effect on the attractor landscape. Using chemical inhibition and overexpression of nodes, we validated that perturbations affect the evolvable core more strongly than the robust neighbor. We also found that the evolvable core has a distinct network structure, which is enriched in feedback loops, and features a higher degree of scale-freeness and longer path lengths connecting the nodes. In addition, the genes with high evolvability scores are associated with evolvability-related properties such as rapid evolvability, low species broadness, and immunity whereas the genes with high robustness scores are associated with robustness-related properties such as slow evolvability, high species broadness, and oncogenes. Intriguingly, US Food and Drug Administration-approved drug targets have high evolvability scores whereas experimental drug targets have high robustness scores. |
---|---|
AbstractList |
Biological systems are known to be both robust and evolvable to internal and external perturbations, but what causes these apparently contradictory properties? We used Boolean network modeling and attractor landscape analysis to investigate the evolvability and robustness of the human signaling network. Our results show that the human signaling network can be divided into an evolvable core where perturbations change the attractor landscape in state space, and a robust neighbor where perturbations have no effect on the attractor landscape. Using chemical inhibition and overexpression of nodes, we validated that perturbations affect the evolvable core more strongly than the robust neighbor. We also found that the evolvable core has a distinct network structure, which is enriched in feedback loops, and features a higher degree of scale-freeness and longer path lengths connecting the nodes. In addition, the genes with high evolvability scores are associated with evolvability-related properties such as rapid evolvability, low species broadness, and immunity whereas the genes with high robustness scores are associated with robustness-related properties such as slow evolvability, high species broadness, and oncogenes. Intriguingly, US Food and Drug Administration-approved drug targets have high evolvability scores whereas experimental drug targets have high robustness scores. Biological systems are known to be both robust and evolvable to internal and external perturbations, but what causes these apparently contradictory properties? We used Boolean network modeling and attractor landscape analysis to investigate the evolvability and robustness of the human signaling network. Our results show that the human signaling network can be divided into an evolvable core where perturbations change the attractor landscape in state space, and a robust neighbor where perturbations have no effect on the attractor landscape. Using chemical inhibition and overexpression of nodes, we validated that perturbations affect the evolvable core more strongly than the robust neighbor. We also found that the evolvable core has a distinct network structure, which is enriched in feedback loops, and features a higher degree of scale-freeness and longer path lengths connecting the nodes. In addition, the genes with high evolvability scores are associated with evolvability-related properties such as rapid evolvability, low species broadness, and immunity whereas the genes with high robustness scores are associated with robustness-related properties such as slow evolvability, high species broadness, and oncogenes. Intriguingly, US Food and Drug Administration-approved drug targets have high evolvability scores whereas experimental drug targets have high robustness scores. Biological systems are known to be both robust and evolvable to internal and external perturbations, but what causes these apparently contradictory properties? We used Boolean network modeling and attractor landscape analysis to investigate the evolvability and robustness of the human signaling network. Our results show that the human signaling network can be divided into an evolvable core where perturbations change the attractor landscape in state space, and a robust neighbor where perturbations have no effect on the attractor landscape. Using chemical inhibition and overexpression of nodes, we validated that perturbations affect the evolvable core more strongly than the robust neighbor. We also found that the evolvable core has a distinct network structure, which is enriched in feedback loops, and features a higher degree of scale-freeness and longer path lengths connecting the nodes. In addition, the genes with high evolvability scores are associated with evolvability-related properties such as rapid evolvability, low species broadness, and immunity whereas the genes with high robustness scores are associated with robustness-related properties such as slow evolvability, high species broadness, and oncogenes. Intriguingly, US Food and Drug Administration-approved drug targets have high evolvability scores whereas experimental drug targets have high robustness scores. Biological systems are known to be robust and evolvable to internal mutations and external environmental changes. What causes these apparently contradictory properties? This study shows that the human signaling network can be decomposed into two structurally distinct subgroups of links that provide both evolvability to environmental changes and robustness against internal mutations. The decomposition of the human signaling network reveals an evolutionary design principle of the network, and also facilitates the identification of potential drug targets. |
Audience | Academic |
Author | Kim, Jeong-Rae Kolch, Walter Vandamme, Drieke Munoz, Amaya Garcia Kim, Junil Cho, Kwang-Hyun |
AuthorAffiliation | 4 Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland 1 Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Yuseong-gu, Daejeon, Republic of Korea 5 School of Medicine and Medical Science, University College Dublin, Dublin, Ireland 3 Department of Mathematics, University of Seoul, Seoul, Republic of Korea University of Virginia, United States of America 2 Systems Biology Ireland, University College Dublin, Dublin, Ireland |
AuthorAffiliation_xml | – name: University of Virginia, United States of America – name: 4 Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland – name: 5 School of Medicine and Medical Science, University College Dublin, Dublin, Ireland – name: 2 Systems Biology Ireland, University College Dublin, Dublin, Ireland – name: 3 Department of Mathematics, University of Seoul, Seoul, Republic of Korea – name: 1 Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Yuseong-gu, Daejeon, Republic of Korea |
Author_xml | – sequence: 1 givenname: Junil surname: Kim fullname: Kim, Junil organization: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Yuseong-gu, Daejeon, Republic of Korea – sequence: 2 givenname: Drieke surname: Vandamme fullname: Vandamme, Drieke organization: Systems Biology Ireland, University College Dublin, Dublin, Ireland – sequence: 3 givenname: Jeong-Rae surname: Kim fullname: Kim, Jeong-Rae organization: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Yuseong-gu, Daejeon, Republic of Korea; Department of Mathematics, University of Seoul, Seoul, Republic of Korea – sequence: 4 givenname: Amaya Garcia surname: Munoz fullname: Munoz, Amaya Garcia organization: Systems Biology Ireland, University College Dublin, Dublin, Ireland – sequence: 5 givenname: Walter surname: Kolch fullname: Kolch, Walter organization: Systems Biology Ireland, University College Dublin, Dublin, Ireland; Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland; School of Medicine and Medical Science, University College Dublin, Dublin, Ireland – sequence: 6 givenname: Kwang-Hyun surname: Cho fullname: Cho, Kwang-Hyun organization: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Yuseong-gu, Daejeon, Republic of Korea |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/25077791$$D View this record in MEDLINE/PubMed |
BookMark | eNqVkk1v1DAQhiNURD_gHyDIEQ672HH8EQ5IVcXHShVIBc7WxLGzXrL21nYW-u9x2LTqHpEPtsbPvDNjv-fFifNOF8VLjJaYcPxu48fgYFjuVGuXGCHCGXlSnGFKyYITKk4enU-L8xg3maGiYc-K04oiznmDz4r3N74dY3I6xhJcV-q9H_bQ2sGmu9KbMq11uR634Mpo-1zOur50Ov324dfz4qmBIeoX835R_Pz08cfVl8X1t8-rq8vrhWKIpoWmnAMXtWGk5RUBxHTVoY60NWItAoNQq4xqDGsAWoyaCmhdUUG7GoyaMi6K1wfd3eCjnMeOEjNBUSUaijKxOhCdh43cBbuFcCc9WPkv4EMvISSrBi0FkJo1tdGq6WqBOsGaXIKrCom2I7TJWh_mamO71Z3SLgUYjkSPb5xdy97vZY0xr6tJ4M0sEPztqGOSWxuVHgZw2o-5b0oxqjhHU9_LA9pDbs0647OiyqvTW6vydxub45dEEFIJQSbtt0cJmUn6T-phjFGuvt_8B_v1mK0PrAo-xqDNw7wYyclt988uJ7fJ2W057dXjt3pIurcX-QsrNdLK |
CitedBy_id | crossref_primary_10_1038_bjc_2017_398 crossref_primary_10_1002_advs_202207322 crossref_primary_10_1093_bioinformatics_btw464 crossref_primary_10_1186_s12918_016_0341_9 crossref_primary_10_1140_epjs_s11734_024_01193_4 crossref_primary_10_3390_e22090986 crossref_primary_10_1002_adma_201906783 crossref_primary_10_22201_ceiich_24485705e_2020_20_71203 crossref_primary_10_1016_j_bpj_2017_10_037 crossref_primary_10_1093_jmcb_mjy019 crossref_primary_10_1039_C5IB00030K crossref_primary_10_1016_j_coph_2019_12_004 crossref_primary_10_1080_10799893_2019_1572762 crossref_primary_10_1038_s41575_018_0007_8 crossref_primary_10_1158_1535_7163_MCT_15_0088 crossref_primary_10_1186_s12918_015_0185_8 crossref_primary_10_1038_srep10305 crossref_primary_10_1002_wsbm_1346 crossref_primary_10_1038_s41598_019_49571_6 crossref_primary_10_1186_s12964_015_0098_6 crossref_primary_10_15430_JCP_2017_22_3_147 |
Cites_doi | 10.1038/nbt1338 10.1042/bj3040809 10.1126/scisignal.2003363 10.1371/journal.pcbi.1000112 10.1093/genetics/130.1.195 10.1073/pnas.95.15.8420 10.1093/genetics/148.3.929 10.1093/bioinformatics/btn229 10.1016/j.cub.2006.08.080 10.1093/nar/gkm958 10.1016/S0303-2647(02)00133-8 10.1038/30918 10.2976/1.3404403 10.1186/1752-0509-7-7 10.1098/rsif.2008.0132.focus 10.1093/bioinformatics/btn060 10.1073/pnas.0503610102 10.1186/1752-0509-1-24 10.1103/PhysRevLett.94.128701 10.1093/nar/gkj021 10.1098/rspb.2007.1137 10.1126/stke.2000.48.re1 10.1016/j.molcel.2004.11.055 10.1016/j.tig.2010.11.002 10.1038/nature08694 10.1371/journal.pcbi.1000550 10.1016/j.jtbi.2006.10.027 10.1093/bioinformatics/btm554 10.1093/nar/gkn665 10.1016/S1074-7613(00)80219-8 10.1038/nrc839 10.1016/j.tig.2010.06.002 10.1073/pnas.0506771102 10.4161/cc.6.1.3593 10.1093/bioinformatics/btn337 10.1093/bioinformatics/bts410 10.1109/JPROC.2002.804686 10.1073/pnas.0404656101 10.1073/pnas.0914180107 10.1038/nrc1300 10.1093/nar/gkm764 10.1371/journal.pone.0055946 10.1016/S0303-2647(02)00137-5 10.1093/nar/gkp967 10.1371/journal.pcbi.0040023 10.1073/pnas.2036429100 10.1093/molbev/msp086 10.1073/pnas.0305937101 10.1111/j.0014-3820.2003.tb00358.x 10.1038/35019019 10.1073/pnas.0705088105 10.1038/nature06847 10.1186/1752-0509-5-50 10.1073/pnas.0501426102 10.1016/j.cell.2004.09.008 10.1038/nrg1272 10.1038/msb.2009.87 10.1038/ng1482 10.1371/journal.pcbi.1000206 10.1093/bioinformatics/btq633 |
ContentType | Journal Article |
Copyright | COPYRIGHT 2014 Public Library of Science 2014 Kim et al 2014 Kim et al 2014 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Kim J, Vandamme D, Kim J-R, Munoz AG, Kolch W, Cho K-H (2014) Robustness and Evolvability of the Human Signaling Network. PLoS Comput Biol 10(7): e1003763. doi:10.1371/journal.pcbi.1003763 |
Copyright_xml | – notice: COPYRIGHT 2014 Public Library of Science – notice: 2014 Kim et al 2014 Kim et al – notice: 2014 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Kim J, Vandamme D, Kim J-R, Munoz AG, Kolch W, Cho K-H (2014) Robustness and Evolvability of the Human Signaling Network. PLoS Comput Biol 10(7): e1003763. doi:10.1371/journal.pcbi.1003763 |
DBID | CGR CUY CVF ECM EIF NPM AAYXX CITATION ISN ISR 7X8 5PM DOA |
DOI | 10.1371/journal.pcbi.1003763 |
DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed CrossRef Gale In Context: Canada Gale In Context: Science MEDLINE - Academic PubMed Central (Full Participant titles) DOAJ Directory of Open Access Journals |
DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) CrossRef MEDLINE - Academic |
DatabaseTitleList | MEDLINE |
Database_xml | – sequence: 1 dbid: DOA name: Directory of Open Access Journals url: https://www.doaj.org/ sourceTypes: Open Website – sequence: 2 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 3 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
DeliveryMethod | fulltext_linktorsrc |
Discipline | Biology |
DocumentTitleAlternate | Robustness and Evolvability of Signaling Network |
EISSN | 1553-7358 |
Editor | Saucerman, Jeffrey J. |
Editor_xml | – sequence: 1 givenname: Jeffrey J. surname: Saucerman fullname: Saucerman, Jeffrey J. |
EndPage | e1003763 |
ExternalDocumentID | 1685028950 oai_doaj_org_article_8a34694fec9d480d8697237c208bd359 A383328839 10_1371_journal_pcbi_1003763 25077791 |
Genre | Research Support, Non-U.S. Gov't Journal Article |
GeographicLocations | South Korea Ireland |
GeographicLocations_xml | – name: Ireland – name: South Korea |
GroupedDBID | --- 123 29O 2WC 3V. 53G 5VS 7X7 88E 8FE 8FG 8FH 8FI 8FJ AAFWJ AAKPC ABDBF ABUWG ACGFO ACIHN ACIWK ACPRK ADBBV ADRAZ AEAQA AENEX AFKRA AFRAH AHMBA ALIPV ALMA_UNASSIGNED_HOLDINGS AOIJS ARAPS AZQEC B0M BAWUL BBNVY BCNDV BENPR BGLVJ BHPHI BPHCQ BVXVI BWKFM C1A CCPQU CGR CS3 CUY CVF DIK DWQXO E3Z EAP EAS EBD EBS ECM EIF EJD EMK EMOBN ESX F5P FPL FYUFA GNUQQ GROUPED_DOAJ GX1 H13 HCIFZ HMCUK HYE IAO IGS INH INR IPNFZ ISN ISR ITC J9A K6V K7- KQ8 LK8 M0N M1P M48 M7P M~E NPM O5R O5S OK1 P2P P62 PGMZT PIMPY PQQKQ PROAC PSQYO PV9 RIG RNS RPM RZL SV3 TR2 TUS UKHRP WOQ WOW XSB ~8M AAYXX CITATION AFPKN 7X8 5PM - AAPBV ABPTK ADACO BBAFP PQEST PQUKI PRINS |
ID | FETCH-LOGICAL-c605t-e577a784f63b723a06e2d0d3b406b0af00bcfc9f69aab1092a542585d4afcb723 |
IEDL.DBID | RPM |
ISSN | 1553-7358 1553-734X |
IngestDate | Fri Nov 26 17:13:24 EST 2021 Tue Oct 22 15:12:32 EDT 2024 Tue Sep 17 21:26:32 EDT 2024 Fri Oct 25 23:13:16 EDT 2024 Tue Nov 12 23:28:55 EST 2024 Thu Aug 01 20:30:59 EDT 2024 Thu Aug 01 19:51:16 EDT 2024 Fri Nov 22 01:13:41 EST 2024 Tue Oct 15 23:48:10 EDT 2024 |
IsDoiOpenAccess | true |
IsOpenAccess | true |
IsPeerReviewed | true |
IsScholarly | true |
Issue | 7 |
Language | English |
License | This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. Creative Commons Attribution License |
LinkModel | DirectLink |
MergedId | FETCHMERGED-LOGICAL-c605t-e577a784f63b723a06e2d0d3b406b0af00bcfc9f69aab1092a542585d4afcb723 |
Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 The authors have declared that no competing interests exist. Conceived and designed the experiments: KHC. Performed the experiments: DV AGM. Analyzed the data: JK DV JRK WK KHC. Contributed reagents/materials/analysis tools: JK DV JRK AGM. Wrote the paper: JK DV JRK WK KHC. Performed simulations: JK JRK. |
OpenAccessLink | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4117429/ |
PMID | 25077791 |
PQID | 1551027700 |
PQPubID | 23479 |
ParticipantIDs | plos_journals_1685028950 doaj_primary_oai_doaj_org_article_8a34694fec9d480d8697237c208bd359 pubmedcentral_primary_oai_pubmedcentral_nih_gov_4117429 proquest_miscellaneous_1551027700 gale_infotracacademiconefile_A383328839 gale_incontextgauss_ISR_A383328839 gale_incontextgauss_ISN_A383328839 crossref_primary_10_1371_journal_pcbi_1003763 pubmed_primary_25077791 |
PublicationCentury | 2000 |
PublicationDate | 2014-07-01 |
PublicationDateYYYYMMDD | 2014-07-01 |
PublicationDate_xml | – month: 07 year: 2014 text: 2014-07-01 day: 01 |
PublicationDecade | 2010 |
PublicationPlace | United States |
PublicationPlace_xml | – name: United States – name: San Francisco, USA |
PublicationTitle | PLoS computational biology |
PublicationTitleAlternate | PLoS Comput Biol |
PublicationYear | 2014 |
Publisher | Public Library of Science Public Library of Science (PLoS) |
Publisher_xml | – name: Public Library of Science – name: Public Library of Science (PLoS) |
References | 15037758 - Proc Natl Acad Sci U S A. 2004 Apr 6;101(14):4781-6 18285369 - Bioinformatics. 2008 Apr 1;24(7):987-94 21146896 - Trends Genet. 2011 Feb;27(2):55-62 19876376 - PLoS Comput Biol. 2009 Oct;5(10):e1000550 10935628 - Nature. 2000 Jul 27;406(6794):378-82 7818485 - Biochem J. 1994 Dec 15;304 ( Pt 3):809-16 17188715 - J Theor Biol. 2007 Apr 7;245(3):433-48 23331499 - BMC Syst Biol. 2013;7:7 23520449 - PLoS One. 2013;8(3):e55946 20090752 - Nature. 2010 Jan 21;463(7279):353-5 16204384 - Proc Natl Acad Sci U S A. 2005 Oct 11;102(41):14497-502 18006545 - Bioinformatics. 2008 Jan 15;24(2):282-4 18467345 - Bioinformatics. 2008 Jul 1;24(13):1516-22 10894168 - Immunity. 2000 Jun;12(6):687-98 18842627 - Nucleic Acids Res. 2009 Jan;37(Database issue):D793-6 12689724 - Biosystems. 2003 May;69(2-3):95-114 14735121 - Nat Rev Genet. 2004 Feb;5(2):101-13 17921997 - Nat Biotechnol. 2007 Oct;25(10):1119-26 18617989 - PLoS Comput Biol. 2008;4(7):e1000112 16174729 - Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):13773-8 15664191 - Mol Cell. 2005 Jan 21;17(2):215-24 19953085 - Mol Syst Biol. 2009;5:331 21632468 - Sci Signal. 2011;4(175):ra35 15903968 - Phys Rev Lett. 2005 Apr 1;94(12):128701 18989390 - PLoS Comput Biol. 2008 Nov;4(11):e1000206 15289608 - Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11531-6 12689727 - Biosystems. 2003 May;69(2-3):143-62 19910364 - Nucleic Acids Res. 2010 Jan;38(Database issue):D5-16 22962472 - Bioinformatics. 2012 Sep 15;28(18):i495-i501 15369668 - Cell. 2004 Sep 17;118(6):675-85 17027474 - Curr Biol. 2006 Oct 10;16(19):R831-4 17962310 - Nucleic Acids Res. 2008 Jan;36(Database issue):D800-8 18250321 - Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):1913-8 17218791 - Cell Cycle. 2007 Jan 1;6(1):3-7 17971325 - Proc Biol Sci. 2008 Jan 7;275(1630):91-100 16155121 - Proc Natl Acad Sci U S A. 2005 Sep 20;102(38):13439-44 21486480 - BMC Syst Biol. 2011;5:50 18421347 - Nature. 2008 Apr 17;452(7189):840-5 19387012 - Mol Biol Evol. 2009 Aug;26(8):1791-801 12094235 - Nat Rev Cancer. 2002 Jul;2(7):489-501 15568024 - Nat Genet. 2005 Jan;37(1):73-6 18266463 - PLoS Comput Biol. 2008 Feb;4(2):e23 9623998 - Nature. 1998 Jun 4;393(6684):440-2 20498084 - Proc Natl Acad Sci U S A. 2010 Jun 8;107(23):10478-83 14657375 - Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):14796-9 11752607 - Sci STKE. 2000 Sep 5;2000(48):re1 1732160 - Genetics. 1992 Jan;130(1):195-204 14993904 - Nat Rev Cancer. 2004 Mar;4(3):227-35 20598394 - Trends Genet. 2010 Sep;26(9):406-14 21119763 - HFSP J. 2010 Jun;4(3-4):105-8 21075744 - Bioinformatics. 2011 Jan 15;27(2):245-51 23169817 - Sci Signal. 2012 Nov 20;5(251):ra83 18508746 - J R Soc Interface. 2008 Aug 6;5 Suppl 1:S85-94 18048412 - Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6 9671692 - Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8420-7 12940355 - Evolution. 2003 Jul;57(7):1498-512 18596076 - Bioinformatics. 2008 Sep 1;24(17):1926-32 16381878 - Nucleic Acids Res. 2006 Jan 1;34(Database issue):D322-6 17547772 - BMC Syst Biol. 2007;1:24 9539414 - Genetics. 1998 Mar;148(3):929-36 A Singh (ref56) 2012; 28 JC Doyle (ref9) 2005; 102 H Kitano (ref40) 2004; 4 GC Nickel (ref57) 2008; 36 YK Kwon (ref4) 2008; 24 M Parter (ref11) 2008; 4 J Stelling (ref1) 2004; 118 G Wang (ref53) 2010; 107 EW Sayers (ref58) 2010; 38 E Bornberg-Bauer (ref7) 2010; 4 D Fazekas (ref54) 2013; 7 S Bornholdt (ref19) 2008; 5 Suppl 1 A Crombach (ref14) 2008; 4 RE Michod (ref50) 2003; 69 T Helikar (ref22) 2008; 105 SI Khakoo (ref39) 2000; 12 YK Kwon (ref3) 2008; 24 J Dong (ref31) 2007; 1 I Shmulevich (ref13) 2005; 102 DS Wishart (ref61) 2008; 36 R Irvine (ref24) 2000; 2000 J Masel (ref6) 2010; 26 JX Zhou (ref52) 2011; 27 D Houle (ref47) 1992; 130 S Kauffman (ref20) 2003; 100 MK Dougherty (ref27) 2005; 17 JA Draghi (ref5) 2010; 463 R Albert (ref8) 2000; 406 MA Yildirim (ref23) 2007; 25 R Nielsen (ref36) 1998; 148 T Hase (ref35) 2009; 5 J Amberger (ref60) 2009; 37 S Huang (ref18) 2005; 94 PD Sniegowski (ref51) 2006; 16 F Li (ref55) 2004; 101 Y Assenov (ref32) 2008; 24 MA Bedau (ref45) 2003; 69 M Kirschner (ref48) 1998; 95 JR Kim (ref37) 2011; 4 DJ Watts (ref34) 1998; 393 I Shmulevich (ref21) 2002; 90 L Viljakainen (ref38) 2009; 26 A Wagner (ref41) 2008; 275 N Kashtan (ref12) 2005; 102 I Vivanco (ref25) 2002; 2 M Isalan (ref15) 2008; 452 J Kim (ref30) 2008; 24 BR Chakravarthy (ref28) 1994; 304 AS Dhillon (ref26) 2007; 6 J Saez-Rodriguez (ref43) 2009; 5 GO Consortium (ref59) 2006; 34 M Marques-Pita (ref42) 2013; 8 TH Kim (ref29) 2011; 27 M Choi (ref17) 2012; 5 A Hintze (ref10) 2008; 4 J Masel (ref49) 2003; 57 M Aldana (ref2) 2007; 245 S Ding (ref16) 2011; 5 AL Barabasi (ref33) 2004; 5 DJ Earl (ref46) 2004; 101 A Aharoni (ref44) 2005; 37 |
References_xml | – volume: 25 start-page: 1119 year: 2007 ident: ref23 article-title: Drug-target network publication-title: Nat Biotechnol doi: 10.1038/nbt1338 contributor: fullname: MA Yildirim – volume: 304 start-page: 809 year: 1994 ident: ref28 article-title: Inactive membrane protein kinase Cs: a possible target for receptor signalling publication-title: Biochem J doi: 10.1042/bj3040809 contributor: fullname: BR Chakravarthy – volume: 5 start-page: ra83 year: 2012 ident: ref17 article-title: Attractor landscape analysis reveals feedback loops in the p53 network that control the cellular response to DNA damage publication-title: Science Signaling doi: 10.1126/scisignal.2003363 contributor: fullname: M Choi – volume: 4 start-page: e1000112 year: 2008 ident: ref14 article-title: Evolution of evolvability in gene regulatory networks publication-title: PLoS Comput Biol doi: 10.1371/journal.pcbi.1000112 contributor: fullname: A Crombach – volume: 130 start-page: 195 year: 1992 ident: ref47 article-title: Comparing evolvability and variability of quantitative traits publication-title: Genetics doi: 10.1093/genetics/130.1.195 contributor: fullname: D Houle – volume: 95 start-page: 8420 year: 1998 ident: ref48 article-title: Evolvability publication-title: Proc Natl Acad Sci U S A doi: 10.1073/pnas.95.15.8420 contributor: fullname: M Kirschner – volume: 148 start-page: 929 year: 1998 ident: ref36 article-title: Likelihood models for detecting positively selected amino acid sites and applications to the HIV-1 envelope gene publication-title: Genetics doi: 10.1093/genetics/148.3.929 contributor: fullname: R Nielsen – volume: 24 start-page: 1516 year: 2008 ident: ref30 article-title: Evolutionary design principles of modules that control cellular differentiation: consequences for hysteresis and multistationarity publication-title: Bioinformatics doi: 10.1093/bioinformatics/btn229 contributor: fullname: J Kim – volume: 16 start-page: R831 year: 2006 ident: ref51 article-title: Evolvability publication-title: Curr Biol doi: 10.1016/j.cub.2006.08.080 contributor: fullname: PD Sniegowski – volume: 36 start-page: D901 year: 2008 ident: ref61 article-title: DrugBank: a knowledgebase for drugs, drug actions and drug targets publication-title: Nucleic Acids Res doi: 10.1093/nar/gkm958 contributor: fullname: DS Wishart – volume: 69 start-page: 95 year: 2003 ident: ref50 article-title: Cooperation and conflict in the evolution of individuality. IV. Conflict mediation and evolvability in Volvox carteri publication-title: Biosystems doi: 10.1016/S0303-2647(02)00133-8 contributor: fullname: RE Michod – volume: 393 start-page: 440 year: 1998 ident: ref34 article-title: Collective dynamics of ‘small-world’ networks publication-title: Nature doi: 10.1038/30918 contributor: fullname: DJ Watts – volume: 4 start-page: 105 year: 2010 ident: ref7 article-title: Robustness versus evolvability: a paradigm revisited publication-title: HFSP J doi: 10.2976/1.3404403 contributor: fullname: E Bornberg-Bauer – volume: 7 start-page: 7 year: 2013 ident: ref54 article-title: SignaLink 2 - a signaling pathway resource with multi-layered regulatory networks publication-title: BMC Syst Biol doi: 10.1186/1752-0509-7-7 contributor: fullname: D Fazekas – volume: 5 Suppl 1 start-page: S85 year: 2008 ident: ref19 article-title: Boolean network models of cellular regulation: prospects and limitations publication-title: J R Soc Interface doi: 10.1098/rsif.2008.0132.focus contributor: fullname: S Bornholdt – volume: 24 start-page: 987 year: 2008 ident: ref4 article-title: Quantitative analysis of robustness and fragility in biological networks based on feedback dynamics publication-title: Bioinformatics doi: 10.1093/bioinformatics/btn060 contributor: fullname: YK Kwon – volume: 102 start-page: 13773 year: 2005 ident: ref12 article-title: Spontaneous evolution of modularity and network motifs publication-title: Proc Natl Acad Sci U S A doi: 10.1073/pnas.0503610102 contributor: fullname: N Kashtan – volume: 1 start-page: 24 year: 2007 ident: ref31 article-title: Understanding network concepts in modules publication-title: BMC Syst Biol doi: 10.1186/1752-0509-1-24 contributor: fullname: J Dong – volume: 94 start-page: 128701 year: 2005 ident: ref18 article-title: Cell fates as high-dimensional attractor states of a complex gene regulatory network publication-title: Phys Rev Lett doi: 10.1103/PhysRevLett.94.128701 contributor: fullname: S Huang – volume: 34 start-page: D322 year: 2006 ident: ref59 article-title: The Gene Ontology (GO) project in 2006 publication-title: Nucleic Acids Res doi: 10.1093/nar/gkj021 contributor: fullname: GO Consortium – volume: 275 start-page: 91 year: 2008 ident: ref41 article-title: Robustness and evolvability: a paradox resolved publication-title: Proc Biol Sci doi: 10.1098/rspb.2007.1137 contributor: fullname: A Wagner – volume: 2000 start-page: re1 year: 2000 ident: ref24 article-title: Nuclear lipid signaling publication-title: Sci STKE doi: 10.1126/stke.2000.48.re1 contributor: fullname: R Irvine – volume: 17 start-page: 215 year: 2005 ident: ref27 article-title: Regulation of Raf-1 by direct feedback phosphorylation publication-title: Mol Cell doi: 10.1016/j.molcel.2004.11.055 contributor: fullname: MK Dougherty – volume: 27 start-page: 55 year: 2011 ident: ref52 article-title: Understanding gene circuits at cell-fate branch points for rational cell reprogramming publication-title: Trends Genet doi: 10.1016/j.tig.2010.11.002 contributor: fullname: JX Zhou – volume: 463 start-page: 353 year: 2010 ident: ref5 article-title: Mutational robustness can facilitate adaptation publication-title: Nature doi: 10.1038/nature08694 contributor: fullname: JA Draghi – volume: 5 start-page: e1000550 year: 2009 ident: ref35 article-title: Structure of protein interaction networks and their implications on drug design publication-title: PLoS Comput Biol doi: 10.1371/journal.pcbi.1000550 contributor: fullname: T Hase – volume: 245 start-page: 433 year: 2007 ident: ref2 article-title: Robustness and evolvability in genetic regulatory networks publication-title: J Theor Biol doi: 10.1016/j.jtbi.2006.10.027 contributor: fullname: M Aldana – volume: 24 start-page: 282 year: 2008 ident: ref32 article-title: Computing topological parameters of biological networks publication-title: Bioinformatics doi: 10.1093/bioinformatics/btm554 contributor: fullname: Y Assenov – volume: 37 start-page: D793 year: 2009 ident: ref60 article-title: McKusick's Online Mendelian Inheritance in Man (OMIM) publication-title: Nucleic Acids Res doi: 10.1093/nar/gkn665 contributor: fullname: J Amberger – volume: 4 start-page: ra35 year: 2011 ident: ref37 article-title: Reduction of complex signaling networks to a representative kernel publication-title: Sci Signal contributor: fullname: JR Kim – volume: 12 start-page: 687 year: 2000 ident: ref39 article-title: Rapid evolution of NK cell receptor systems demonstrated by comparison of chimpanzees and humans publication-title: Immunity doi: 10.1016/S1074-7613(00)80219-8 contributor: fullname: SI Khakoo – volume: 2 start-page: 489 year: 2002 ident: ref25 article-title: The phosphatidylinositol 3-Kinase AKT pathway in human cancer publication-title: Nat Rev Cancer doi: 10.1038/nrc839 contributor: fullname: I Vivanco – volume: 26 start-page: 406 year: 2010 ident: ref6 article-title: Robustness and evolvability publication-title: Trends Genet doi: 10.1016/j.tig.2010.06.002 contributor: fullname: J Masel – volume: 102 start-page: 13439 year: 2005 ident: ref13 article-title: Eukaryotic cells are dynamically ordered or critical but not chaotic publication-title: Proc Natl Acad Sci U S A doi: 10.1073/pnas.0506771102 contributor: fullname: I Shmulevich – volume: 6 start-page: 3 year: 2007 ident: ref26 article-title: Phosphatase and feedback regulation of Raf-1 signaling publication-title: Cell Cycle doi: 10.4161/cc.6.1.3593 contributor: fullname: AS Dhillon – volume: 24 start-page: 1926 year: 2008 ident: ref3 article-title: Coherent coupling of feedback loops: a design principle of cell signaling networks publication-title: Bioinformatics doi: 10.1093/bioinformatics/btn337 contributor: fullname: YK Kwon – volume: 28 start-page: i495 year: 2012 ident: ref56 article-title: Boolean approach to signalling pathway modelling in HGF-induced keratinocyte migration publication-title: Bioinformatics doi: 10.1093/bioinformatics/bts410 contributor: fullname: A Singh – volume: 90 start-page: 1778 year: 2002 ident: ref21 article-title: From Boolean to probabilistic Boolean networks as models of genetic regulatory networks publication-title: Proceedings of the Ieee doi: 10.1109/JPROC.2002.804686 contributor: fullname: I Shmulevich – volume: 101 start-page: 11531 year: 2004 ident: ref46 article-title: Evolvability is a selectable trait publication-title: Proc Natl Acad Sci U S A doi: 10.1073/pnas.0404656101 contributor: fullname: DJ Earl – volume: 107 start-page: 10478 year: 2010 ident: ref53 article-title: Process-based network decomposition reveals backbone motif structure publication-title: Proc Natl Acad Sci U S A doi: 10.1073/pnas.0914180107 contributor: fullname: G Wang – volume: 4 start-page: 227 year: 2004 ident: ref40 article-title: Cancer as a robust system: implications for anticancer therapy publication-title: Nat Rev Cancer doi: 10.1038/nrc1300 contributor: fullname: H Kitano – volume: 36 start-page: D800 year: 2008 ident: ref57 article-title: Human PAML browser: a database of positive selection on human genes using phylogenetic methods publication-title: Nucleic Acids Res doi: 10.1093/nar/gkm764 contributor: fullname: GC Nickel – volume: 8 start-page: e55946 year: 2013 ident: ref42 article-title: Canalization and control in automata networks: body segmentation in Drosophila melanogaster publication-title: PLoS One doi: 10.1371/journal.pone.0055946 contributor: fullname: M Marques-Pita – volume: 69 start-page: 143 year: 2003 ident: ref45 article-title: Evolution of evolvability via adaptation of mutation rates publication-title: Biosystems doi: 10.1016/S0303-2647(02)00137-5 contributor: fullname: MA Bedau – volume: 38 start-page: D5 year: 2010 ident: ref58 article-title: Database resources of the National Center for Biotechnology Information publication-title: Nucleic Acids Res doi: 10.1093/nar/gkp967 contributor: fullname: EW Sayers – volume: 4 start-page: e23 year: 2008 ident: ref10 article-title: Evolution of complex modular biological networks publication-title: PLoS Comput Biol doi: 10.1371/journal.pcbi.0040023 contributor: fullname: A Hintze – volume: 100 start-page: 14796 year: 2003 ident: ref20 article-title: Random Boolean network models and the yeast transcriptional network publication-title: Proc Natl Acad Sci U S A doi: 10.1073/pnas.2036429100 contributor: fullname: S Kauffman – volume: 26 start-page: 1791 year: 2009 ident: ref38 article-title: Rapid evolution of immune proteins in social insects publication-title: Mol Biol Evol doi: 10.1093/molbev/msp086 contributor: fullname: L Viljakainen – volume: 101 start-page: 4781 year: 2004 ident: ref55 article-title: The yeast cell-cycle network is robustly designed publication-title: Proc Natl Acad Sci U S A doi: 10.1073/pnas.0305937101 contributor: fullname: F Li – volume: 57 start-page: 1498 year: 2003 ident: ref49 article-title: The evolution of the evolvability properties of the yeast prion [PSI+] publication-title: Evolution doi: 10.1111/j.0014-3820.2003.tb00358.x contributor: fullname: J Masel – volume: 406 start-page: 378 year: 2000 ident: ref8 article-title: Error and attack tolerance of complex networks publication-title: Nature doi: 10.1038/35019019 contributor: fullname: R Albert – volume: 105 start-page: 1913 year: 2008 ident: ref22 article-title: Emergent decision-making in biological signal transduction networks publication-title: Proc Natl Acad Sci U S A doi: 10.1073/pnas.0705088105 contributor: fullname: T Helikar – volume: 452 start-page: 840 year: 2008 ident: ref15 article-title: Evolvability and hierarchy in rewired bacterial gene networks publication-title: Nature doi: 10.1038/nature06847 contributor: fullname: M Isalan – volume: 5 start-page: 50 year: 2011 ident: ref16 article-title: Recipes and mechanisms of cellular reprogramming: a case study on budding yeast Saccharomyces cerevisiae publication-title: BMC Syst Biol doi: 10.1186/1752-0509-5-50 contributor: fullname: S Ding – volume: 102 start-page: 14497 year: 2005 ident: ref9 article-title: The “robust yet fragile” nature of the Internet publication-title: Proc Natl Acad Sci U S A doi: 10.1073/pnas.0501426102 contributor: fullname: JC Doyle – volume: 118 start-page: 675 year: 2004 ident: ref1 article-title: Robustness of cellular functions publication-title: Cell doi: 10.1016/j.cell.2004.09.008 contributor: fullname: J Stelling – volume: 5 start-page: 101 year: 2004 ident: ref33 article-title: Network biology: understanding the cell's functional organization publication-title: Nat Rev Genet doi: 10.1038/nrg1272 contributor: fullname: AL Barabasi – volume: 5 start-page: 331 year: 2009 ident: ref43 article-title: Discrete logic modelling as a means to link protein signalling networks with functional analysis of mammalian signal transduction publication-title: Mol Syst Biol doi: 10.1038/msb.2009.87 contributor: fullname: J Saez-Rodriguez – volume: 37 start-page: 73 year: 2005 ident: ref44 article-title: The ‘evolvability’ of promiscuous protein functions publication-title: Nat Genet doi: 10.1038/ng1482 contributor: fullname: A Aharoni – volume: 4 start-page: e1000206 year: 2008 ident: ref11 article-title: Facilitated variation: how evolution learns from past environments to generalize to new environments publication-title: PLoS Comput Biol doi: 10.1371/journal.pcbi.1000206 contributor: fullname: M Parter – volume: 27 start-page: 245 year: 2011 ident: ref29 article-title: Evolutionary design principles and functional characteristics based on kingdom-specific network motifs publication-title: Bioinformatics doi: 10.1093/bioinformatics/btq633 contributor: fullname: TH Kim |
SSID | ssj0035896 |
Score | 2.2962425 |
Snippet | Biological systems are known to be both robust and evolvable to internal and external perturbations, but what causes these apparently contradictory properties?... Biological systems are known to be both robust and evolvable to internal and external perturbations, but what causes these apparently contradictory... |
SourceID | plos doaj pubmedcentral proquest gale crossref pubmed |
SourceType | Open Website Open Access Repository Aggregation Database Index Database |
StartPage | e1003763 |
SubjectTerms | Algorithms Behavior Biology and Life Sciences Cellular signal transduction Decomposition Drug Discovery Evolution, Molecular FDA approval Genes Humans Models, Biological Physiological aspects Signal transduction Signal Transduction - genetics Signal Transduction - physiology Simulation Technological planning Telephone number portability Values |
SummonAdditionalLinks | – databaseName: DOAJ Directory of Open Access Journals dbid: DOA link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1LixQxEA4yIHgR39u-iCJ4ajfdSXcSb6u4rIJ7WF2YW8hTF5buwZ5Z2H-_VZ2eYVoUL15nqg9Vlap8Raq-IuSNlYCB6yBL3YZQCqcC5kFessC0l0IrJ3DA-etpe3Iuviyb5d6qL-wJy_TA2XCHynKo4ESKXgehWFAt7smSvmbKBd7k0T1Wb4upnIN5o8bNXLgUp5RcLKehOS6rw8lH71beXWCPQKYA3buURu7-XYZerC774U_w8_cuyr1r6fgeuTvhSXqU9bhPbsXuAbmdN0xePyTvz3q3GdaYz6jtAo2Qja4yNfc17RMF-EfHNX0UGzkszqbTLneGPyLnx5--fzwpp3UJpYeaZF3GRkorlUgtd2Aiy9pYBxa4gzvbMZsYcz55nVptrauYrm0DAauaIGzy-MVjsuj6Lh4Q2soQdOChtoC3tIISEIt8CfEbbbIyFaTc2susMiuGGZ_GJFQTWXGD9jWTfQvyAY26k0VO6_EH8LSZPG3-5emCvEaXGGSt6LAt5ofdDIP5_O3UHEGdzXFv8t-FzmZCbyeh1IPrvJ1GEUB5ZMOaSR6g_7dKDaZqVYOPsw0ryKvtmTAQkvjOYrvYb0AGUCg-jTOQeZLPyE5zQJxSSl0VRM5Oz8w083-6i58j7beooHqs9dP_Yctn5A4gP5H7jp-TxfrXJr4AdLV2L8dAugH4AB8j priority: 102 providerName: Directory of Open Access Journals – databaseName: Scholars Portal Open Access Journals dbid: M48 link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjV3di9QwEA_niuCL-H31iyiCTz3SJm0SQeQUj1O4ezhd2LeQj-bu4GjX7a64_70z_Vis3IGv7bSQSWbmN8xkfoS8tRIwcB5kqssQUuFUQD_IUxaY9lJo5QRecD45LY_n4tuiWOyRkbN1UGB7bWqHfFLz1dXB75_bj2DwHzrWBpmNHx0svbvEqj_azC1yO4fYiE1eJ2JXV-CF6hi7kCwnlVwshst0N_1lEqy6mf47zz1bXjXtdbD03-7Kv8LV0X1yb8CZ9LA_GA_IXlU_JHd65sntI_L-rHGbdo1-jto60Aq81K9-ZPeWNpECLKQdfR_FBg-Ld9Zp3XeMPybzoy8_Ph-nA41C6iFXWadVIaWVSsSSO5lzy8oqDyxwB7HcMRsZcz56HUttrcuYzm0BhqyKIGz0-MUTMqubutontJQh6MBDbgGHaQWpISb_Euy6stHKmJB01JdZ9tMyTFcyk5Bl9As3qF8z6Dchn1CpO1mcdd09aFbnZjAdoyyHHF7EyusgFAuqRKY06XOmXOCFTsgb3BKD0yxqbJc5t5u2NV-_n5pDyL858infLHQ2EXo3CMUGts7b4YoCLB6nZE0k93H_x0W1JitVgUXbgiXk9XgmDJgq1l9sXTUbkAF0iiVzBjJP-zOyWzkgUSmlzhIiJ6dnoprpm_ryohsHLjLIKnP97H_U8JzcBcQn-n7jF2S2Xm2ql4Cq1u5VZyh_AIToH0c priority: 102 providerName: Scholars Portal |
Title | Robustness and evolvability of the human signaling network |
URI | https://www.ncbi.nlm.nih.gov/pubmed/25077791 https://search.proquest.com/docview/1551027700 https://pubmed.ncbi.nlm.nih.gov/PMC4117429 https://doaj.org/article/8a34694fec9d480d8697237c208bd359 http://dx.doi.org/10.1371/journal.pcbi.1003763 |
Volume | 10 |
hasFullText | 1 |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3da9swEBdtxmAvY9_NugVvDPbkRLFkS9pbW5J1g4SSrpA3IVl2GmjtUCeF_ve7k-1Qj-1lL36wz9i6L_1OOt0R8sUIwMCRE6FKnAu5lQ79IAupoyoVXEnL8YDzbJ6cX_Gfy3h5QOL2LIxP2k_teljc3A6L9bXPrdzcpqM2T2x0MTvjY8DRkRodkkOYftsQvXa_LJa-KRf2wwkF48vmvBwT41EjnuEGPzDG0isJ9tEBFCCEr9L5aGryFfz3frq3uSmrv4HQP3MpH01O0xfkeYMqg5P671-Sg6x4RZ7WfSYfXpNvi9Luqi16tcAULpiAT7qvC3Q_BGUeAAgM_Gp-cLleITIvVsG8zg9_Q66mk19n52HTNCFMITLZhlkshBGS5wmzImKGJlnkqGMWZm5LTU6pTfNU5Ykyxo6pikwMZitjx02e4htvSa8oi-yIBIlwTjnmIgOoS0kIBDHUF2DFmcmNyPskbPmlN3VtDO03yATEFPXANbJaN6zuk1Nk6p4WK1v7G-XdSjfy1dIwiNh5nqXKcUmdTLAvmkgjKq1jseqTzygSjbUrCkyOWZldVekfl3N9AtE2w-7J_yZadIi-NkR5CaJLTXMgAQaPNbE6lEco_3ZQlR4nMsYt2pj2yadWJzQYJu62mCIrd0ADWBQ3yCnQvKt1ZD_yVuP6RHS0p8Oa7hOwBV_8u9H99__95jF5BqCP1ynHH0hve7fLPgKw2toBmNNSwFVOvw_Ik9PJ_GIx8IsUcJ1xOfCG9htPfSUp |
link.rule.ids | 230,314,727,780,784,864,885,2102,2221,24318,27924,27925,31720,33374,33745,53791,53793 |
linkProvider | National Library of Medicine |
linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3JbtswECVSF0V7Kbom6qoWBXqSTYmUSPaWBgmcNjaKLIBvBBfJNZBIRmwHyN9nRosRFe2lV3sEm7PxjTh8Q8gXIwADJ15EKvM-4lZ6zIMsop4qJ7iSluMF58k0G1_wH7N0tkPS7i5M3bTv7GJYXl4Ny8XvurdyeeVGXZ_Y6NfkgMeAoxM1ekAepkyouCvSmwTMUlmP5cKJOJFgfNbemGMiHrUGGi7xJ2IkX8lwkg7gACFqns57m1PN4b_N1IPlZbX6Gwz9s5vy3vZ09Iw8bXFluN_8_-dkJy9fkEfNpMnbl-TbaWU3qzXmtdCUPjyErHTTUHTfhlURAgwM6_f54dlijti8nIfTpkP8Fbk4Ojw_GEft2ITIQW2yjvJUCCMkLzJmRcIMzfLEU88s7N2WmoJS6wqnikwZY2OqEpNC4MrUc1M4fOI1GZRVme-RMBPeK898YgB3KQmlIBb7AuI4N4URRUCiTl962bBj6PqITEBV0Sxco6p1q-qAfEelbmWR27r-oLqe69bCWhoGNTsvcqc8l9TLDCejCZdQaT1LVUA-o0k0sleU2B4zN5vVSh-fTfU-1NsM5yf_W-i0J_S1FSoqMJ0z7ZUEWDyyYvUk99D-3aJWOs5kioe0KQ3Ip84nNIQmnreYMq82IANoFI_IKcjsNj6yXXnncQERPe_pqab_DURDTf_dev-b_37yI3k8Pp-c6JPj6c-35AlAQN40IL8jg_X1Jn8PMGttP9RBdQdH5SNI |
linkToPdf | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3db9MwELegCMQL4nvlMyAkntI4sRPbvI2xagNWTRuT-mb5Iy6VtqRaW6T999zlo2oRvPCanBXdp38Xn-8I-WAEYODMi1gV3sfcSo9xkMXUU-UEV9JyvOB8MimOLvjXaT7dGvXVFO07Ox9Vl1ejav6zqa1cXLmkrxNLTk8OeAo4OlPJwofkNrmTMzCyPlFvgzDLZTOaC6fixILxaXdrjok06ZQ0WuBnUmzAUuA0HcACQjS9Orc2qKaP_yZaDxaX9fJvUPTPisqtLWr8kDzosGW03_LwiNwqq8fkbjtt8uYJ-XRW2_VyhbEtMpWPDiEy_WrbdN9EdYgACkbNP_3ofD5DfF7NoklbJf6UXIwPfxwcxd3ohNhBfrKKy1wIIyQPBbMiY4YWZeapZxb2b0tNoNS64FQolDE2pSozOTivzD03weGKZ2RQ1VW5R6JCeK8885kB7KUkpIOY8Avw5dIEI8KQxL289KLtkKGbYzIBmUXLuEZR607UQ_IZhbqhxf7WzYP6eqY7LWtpGOTtPJROeS6plwVORxMuo9J6lqsheY8q0djBosISmZlZL5f6-Hyi9yHnZjhD-d9EZztEHzuiUIPqnOmuJQDz2Blrh3IP9d8ztdRpIXM8qM3pkLzrbUKDe-KZi6nKeg00gEjxmJwCzfPWRjac9xY3JGLHenZEs_sGPKJpAd55wIv_XvmW3Dv9MtbfjyffXpL7gAJ5W4P8igxW1-vyNSCtlX3T-NRvdwYkWw |
openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Robustness+and+evolvability+of+the+human+signaling+network&rft.jtitle=PLoS+computational+biology&rft.au=Kim%2C+Junil&rft.au=Vandamme%2C+Drieke&rft.au=Kim%2C+Jeong-Rae&rft.au=Munoz%2C+Amaya+Garcia&rft.date=2014-07-01&rft.pub=Public+Library+of+Science&rft.issn=1553-734X&rft.eissn=1553-7358&rft.volume=10&rft.issue=7&rft_id=info:doi/10.1371%2Fjournal.pcbi.1003763&rft.externalDBID=ISN&rft.externalDocID=A383328839 |
thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1553-7358&client=summon |
thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1553-7358&client=summon |
thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1553-7358&client=summon |