{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T04:10:06Z","timestamp":1772165406809,"version":"3.50.1"},"reference-count":63,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Syst Biol"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Tardigrades are multicellular organisms, resistant to extreme environmental changes such as heat, drought, radiation and freezing. They outlast these conditions in an inactive form (tun) to escape damage to cellular structures and cell death. Tardigrades are apparently able to prevent or repair such damage and are therefore a crucial model organism for stress tolerance. Cultures of the tardigrade\n                      <jats:italic>Milnesium tardigradum<\/jats:italic>\n                      were dehydrated by removing the surrounding water to induce tun formation. During this process and the subsequent rehydration, metabolites were measured in a time series by GC-MS. Additionally expressed sequence tags are available, especially libraries generated from the active and inactive state. The aim of this integrated analysis is to trace changes in tardigrade metabolism and identify pathways responsible for their extreme resistance against physical stress.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In this study we propose a novel integrative approach for the analysis of metabolic networks to identify modules of joint shifts on the transcriptomic and metabolic levels. We derive a tardigrade-specific metabolic network represented as an undirected graph with 3,658 nodes (metabolites) and 4,378 edges (reactions). Time course metabolite profiles are used to score the network nodes showing a significant change over time. The edges are scored according to information on enzymes from the EST data. Using this combined information, we identify a key subnetwork (functional module) of concerted changes in metabolic pathways, specific for de- and rehydration. The module is enriched in reactions showing significant changes in metabolite levels and enzyme abundance during the transition. It resembles the cessation of a measurable metabolism (e.g. glycolysis and amino acid anabolism) during the tun formation, the production of storage metabolites and bioprotectants, such as DNA stabilizers, and the generation of amino acids and cellular components from monosaccharides as carbon and energy source during rehydration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The functional module identifies relationships among changed metabolites (e.g. spermidine) and reactions and provides first insights into important altered metabolic pathways. With sparse and diverse data available, the presented integrated metabolite network approach is suitable to integrate all existing data and analyse it in a combined manner.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/1752-0509-6-72","type":"journal-article","created":{"date-parts":[[2012,6,28]],"date-time":"2012-06-28T05:01:55Z","timestamp":1340859715000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Integrated pathway modules using time-course metabolic profiles and EST data from Milnesium tardigradum"],"prefix":"10.1186","volume":"6","author":[{"given":"Daniela","family":"Beisser","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus A","family":"Grohme","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joachim","family":"Kopka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcus","family":"Frohme","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralph O","family":"Schill","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steffen","family":"Hengherr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Dandekar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gunnar W","family":"Klau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcus","family":"Dittrich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tobias","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2012,6,19]]},"reference":[{"key":"1018_CR1","first-page":"203","volume-title":"Modena: Societ\u00e0 Tipografica","author":"L Spallanzani","year":"1776","unstructured":"Spallanzani L: Opuscoli di Fisica Animale e Vegetabile. Modena: Societ\u00e0 Tipografica 1776, 203-285."},{"key":"1018_CR2","first-page":"501","volume":"45","author":"H Baumann","year":"1922","unstructured":"Baumann H: Die Anabiose der Tardigraden. Zool Jahrb 1922, 45: 501-556.","journal-title":"Zool Jahrb"},{"key":"1018_CR3","first-page":"235","volume":"23","author":"P Rahm","year":"1921","unstructured":"Rahm P: Effect of very low temperatures on the fauna of moss. Proc K Ned AkadWet Ser C Biol Med Sci 1921, 23: 235-248.","journal-title":"Proc K Ned AkadWet Ser C Biol Med Sci"},{"key":"1018_CR4","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1007\/978-3-642-12422-8_8","volume-title":"Dormancy and Resistance in Harsh Environments, Volume 21 of Topics in Current Genetics","author":"R Schill","year":"2010","unstructured":"Schill R: Anhydrobiotic Abilities of Tardigrades. In Dormancy and Resistance in Harsh Environments, Volume 21 of Topics in Current Genetics. Edited by: Lubzens E, Cerda J, Clark M. Heidelberg: Springer Berlin; 2010:133-146. [http:\/\/dx.doi.org\/10.1007\/978-3-642-12422-8\u2216_8]"},{"issue":"4","key":"1018_CR5","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1016\/S1096-4959(01)00300-1","volume":"128","author":"JS Clegg","year":"2001","unstructured":"Clegg JS: Cryptobiosis\u2013a peculiar state of biological organization. Comp Biochem Physiol B Biochem Mol Biol 2001,128(4):613-624. 10.1016\/S1096-4959(01)00300-1","journal-title":"Comp Biochem Physiol B Biochem Mol Biol"},{"issue":"Suppl","key":"1018_CR6","first-page":"37","volume":"32","author":"JH Crowe","year":"1975","unstructured":"Crowe JH: The physiology of cryptobiosis in tardigrades. Memorie dell\u2019Istituto Italiano di Idrobiologica 1975,32(Suppl):37-59.","journal-title":"Memorie dell\u2019Istituto Italiano di Idrobiologica"},{"key":"1018_CR7","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1111\/j.1742-4658.2007.06198.x","volume":"275","author":"S Hengherr","year":"2008","unstructured":"Hengherr S, Heyer AG, K\u00f6hler HR, Schill RO: Trehalose and anhydrobiosis in tardigrades - evidence for divergence in responses to dehydration. FEBS J 2008, 275: 281-288. 10.1111\/j.1742-4658.2007.06198.x","journal-title":"FEBS J"},{"key":"1018_CR8","volume-title":"Greenland Excursion,","author":"P Westh","year":"1988","unstructured":"Westh P, Raml\u00f8v H: Cryptobiosis in Arctic tardigrades with special attention to the appearance of trehalose. In Greenland Excursion,. Institute of polar Ecology. Kiel University; 1988."},{"key":"1018_CR9","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1002\/jez.1402580305","volume":"258","author":"P Westh","year":"1991","unstructured":"Westh P, Raml\u00f8v H: Trehalose accumulation in the tardigrade Adorybiotus coronifer during anhydrobiosis. J Exp Zool 1991, 258: 303-311. 10.1002\/jez.1402580305","journal-title":"J Exp Zool"},{"key":"1018_CR10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.2174\/1874336601003010001","volume":"3","author":"KI J\u00f6nsson","year":"2010","unstructured":"J\u00f6nsson KI, Persson O: Trehalose in three species of desiccation tolerant tardigrades. Open Zool J 2010, 3: 1-5. 10.2174\/1874336601003010001","journal-title":"Open Zool J"},{"issue":"4","key":"1018_CR11","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1016\/j.cbpb.2006.10.111","volume":"146","author":"KI J\u00f6nsson","year":"2007","unstructured":"J\u00f6nsson KI, Schill RO: Induction of Hsp70 by desiccation, ionising radiation and heat-shock in the eutardigrade Richtersius coronifer. Comp Biochem Physiol B Biochem Mol Biol 2007,146(4):456-460. [http:\/\/dx.doi.org\/10.1016\/j.cbpb.2006.10.111] 10.1016\/j.cbpb.2006.10.111","journal-title":"Comp Biochem Physiol B Biochem Mol Biol"},{"key":"1018_CR12","first-page":"679","volume":"44","author":"B McGee","year":"2004","unstructured":"McGee B, Schill RO, Tunnacliffe A: Hydrophilic proteins in invertebrate anhydrobiosis. Integr Comp Biol 2004, 44: 679-679.","journal-title":"Integr Comp Biol"},{"key":"1018_CR13","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1078\/0044-5231-00062","volume":"240","author":"H Raml\u00f8v","year":"2001","unstructured":"Raml\u00f8v H, Westh P: Cryptobiosis in the Eutardigrade Adorybiotus (Richtersius) coronifer: tolerance to alcohols temperature and de novo protein synthesis. Zoologischer Anzeiger 2001, 240: 517-523. 10.1078\/0044-5231-00062","journal-title":"Zoologischer Anzeiger"},{"issue":"4","key":"1018_CR14","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1007\/s12192-009-0158-1","volume":"15","author":"A Reuner","year":"2010","unstructured":"Reuner A, Hengherr S, Mali B, F\u00f6rster F, Arndt D, Reinhardt R, Dandekar T, Frohme M, Br\u00fcmmer F, Schill RO: Stress response in tardigrades: differential gene expression of molecular chaperones. Cell Stress Chaperones 2010,15(4):423-430. [http:\/\/dx.doi.org\/10.1007\/s12192-009-0158-1] 10.1007\/s12192-009-0158-1","journal-title":"Cell Stress Chaperones"},{"issue":"Pt 10","key":"1018_CR15","doi-asserted-by":"publisher","first-page":"1607","DOI":"10.1242\/jeb.00935","volume":"207","author":"RO Schill","year":"2004","unstructured":"Schill RO, Steinbr\u00fcck GHB, K\u00f6hler HR: Stress gene (hsp70) sequences and quantitative expression in Milnesium tardigradum (Tardigrada) during active and cryptobiotic stages. J Exp Biol 2004,207(Pt 10):1607-1613.","journal-title":"J Exp Biol"},{"key":"1018_CR16","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1111\/j.1439-0469.2010.00608.x","volume":"49","author":"E Schokraie","year":"2011","unstructured":"Schokraie E, Hotz-Wagenblatt A, Warnken U, Frohme M, Dandekar T, Schill RO, Schn\u00f6lzer M: Investigating heat shock proteins of tardigrades in active versus anhydrobiotic state using shotgun proteomics. Journal of Zoological Systematics and Evolutionary Research 2011, 49: 111-119. [http:\/\/dx.doi.org\/10.1111\/j.1439-0469.2010.00608.x]","journal-title":"Journal of Zoological Systematics and Evolutionary Research"},{"issue":"1","key":"1018_CR17","first-page":"211","volume":"71","author":"T Altiero","year":"2012","unstructured":"Altiero T, Guidetti R, Boschini D, Rebecchi L: Heat shock proteins in encysted and anhydrobiotic eutardigrades. J LImnol 2012,71(1):211-215.","journal-title":"J LImnol"},{"key":"1018_CR18","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1186\/1471-2164-11-168","volume":"11","author":"B Mali","year":"2010","unstructured":"Mali B, Grohme MA, F\u00f6rster F, Dandekar T, Schn\u00f6lzer M, Reuter D, We\u0142nicz W, Schill RO, Frohme M: Transcriptome survey of the anhydrobiotic tardigrade Milnesium tardigradum in comparison with Hypsibius dujardini and Richtersius coronifer. BMC Genomics 2010, 11: 168. [http:\/\/dx.doi.org\/10.1186\/1471-2164-11-168] 10.1186\/1471-2164-11-168","journal-title":"BMC Genomics"},{"key":"1018_CR19","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1111\/j.1439-0469.2010.00609.x","volume":"49","author":"F F\u00f6rster","year":"2011","unstructured":"F\u00f6rster F, Beisser D, Frohme M, Schill RO, Dandekar T: Bioinformatics identifies tardigrade molecular adaptations including the DNA-j family and first steps towards dynamical modelling. J Zoological Syst Evolutionary Res 2011, 49: 120-126. [http:\/\/dx.doi.org\/10.1111\/j.1439-0469.2010.00609.x]","journal-title":"J Zoological Syst Evolutionary Res"},{"issue":"2","key":"1018_CR20","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1089\/cmb.2006.13.133","volume":"13","author":"J Scott","year":"2006","unstructured":"Scott J, Ideker T, Karp RM, Sharan R: Efficient algorithms for detecting signaling pathways in protein interaction networks. J Comput Biol 2006,13(2):133-144. [http:\/\/dx.doi.org\/10.1089\/cmb.2006.13.133] 10.1089\/cmb.2006.13.133","journal-title":"J Comput Biol"},{"issue":"13","key":"1018_CR21","doi-asserted-by":"publisher","first-page":"i223","DOI":"10.1093\/bioinformatics\/btn161","volume":"24","author":"MT Dittrich","year":"2008","unstructured":"Dittrich MT, Klau GW, Rosenwald A, Dandekar T, M\u00fcller T: Identifying functional modules in protein-protein interaction networks: an integrated exact approach. Bioinformatics 2008,24(13):i223-i231. [http:\/\/dx.doi.org\/10.1093\/bioinformatics\/btn161] 10.1093\/bioinformatics\/btn161","journal-title":"Bioinformatics"},{"issue":"Suppl 1","key":"1018_CR22","doi-asserted-by":"publisher","first-page":"S233","DOI":"10.1093\/bioinformatics\/18.suppl_1.S233","volume":"18","author":"T Ideker","year":"2002","unstructured":"Ideker T, Ozier O, Schwikowski B, Siegel AF: Discovering regulatory and signalling circuits in molecular interaction networks. Bioinformatics 2002,18(Suppl 1):S233-S240. 10.1093\/bioinformatics\/18.suppl_1.S233","journal-title":"Bioinformatics"},{"key":"1018_CR23","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/1752-0509-1-8","volume":"1","author":"I Ulitsky","year":"2007","unstructured":"Ulitsky I, Shamir R: Identification of functional modules using network topology and high-throughput data. BMC Syst Biol 2007, 1: 8. [http:\/\/dx.doi.org\/10.1186\/1752-0509-1-8] 10.1186\/1752-0509-1-8","journal-title":"BMC Syst Biol"},{"key":"1018_CR24","volume-title":"Bioinformatics","author":"D Beisser","year":"2012","unstructured":"Beisser D, Brunkhorst S, Dandekar T, Klau GW, Dittrich MT, M\u00fcller T: Robustness and accuracy of functional modules in integrated network analysis. Bioinformatics 2012, in press.. [http:\/\/dx.doi.org\/10.1093\/bioinformatics\/bts265]"},{"key":"1018_CR25","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1186\/1752-0509-4-180","volume":"4","author":"A Pop","year":"2010","unstructured":"Pop A, Huttenhower C, Iyer-Pascuzzi A, Benfey PN, Troyanskaya OG: Integrated functional networks of process, tissue, and developmental stage specific interactions in Arabidopsis thaliana. BMC Syst Biol 2010, 4: 180. [http:\/\/dx.doi.org\/10.1186\/1752-0509-4-180] 10.1186\/1752-0509-4-180","journal-title":"BMC Syst Biol"},{"issue":"3","key":"1018_CR26","doi-asserted-by":"publisher","first-page":"R24","DOI":"10.1186\/gb-2011-12-3-r24","volume":"12","author":"A Cecil","year":"2011","unstructured":"Cecil A, Rikanovi\u0107 C, Ohlsen K, Liang C, Bernhardt J, Oelschlaeger TA, Gulder T, Bringmann G, Holzgrabe U, Unger M, Dandekar T: Modeling antibiotic and cytotoxic effects of the dimeric isoquinoline IQ-143 on metabolism and its regulation in Staphylococcus aureus, Staphylococcus epidermidis and human cells. Genome Biol 2011,12(3):R24. [http:\/\/dx.doi.org\/10.1186\/gb-2011-12-3-r24] 10.1186\/gb-2011-12-3-r24","journal-title":"Genome Biol"},{"issue":"2","key":"1018_CR27","doi-asserted-by":"publisher","first-page":"e1000692","DOI":"10.1371\/journal.pcbi.1000692","volume":"6","author":"RC Deo","year":"2010","unstructured":"Deo RC, Hunter L, Lewis GD, Pare G, Vasan RS, Chasman D, Wang TJ, Gerszten RE, Roth FP: Interpreting metabolomic profiles using unbiased pathway models. PLoS Comput Biol 2010,6(2):e1000692. [http:\/\/dx.doi.org\/10.1371\/journal.pcbi.1000692] 10.1371\/journal.pcbi.1000692","journal-title":"PLoS Comput Biol"},{"key":"1018_CR28","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1038\/msb.2009.77","volume":"5","author":"MA Oberhardt","year":"2009","unstructured":"Oberhardt MA, Palsson B, Papin JA: Applications of genome-scale metabolic reconstructions. Mol Syst Biol 2009, 5: 320. [http:\/\/dx.doi.org\/10.1038\/msb.2009.77]","journal-title":"Mol Syst Biol"},{"key":"1018_CR29","doi-asserted-by":"publisher","first-page":"2006.0034","DOI":"10.1038\/msb4100074","volume":"2","author":"A K\u00fcmmel","year":"2006","unstructured":"K\u00fcmmel A, Panke S, Heinemann M: Putative regulatory sites unraveled by network-embedded thermodynamic analysis of metabolome data. Mol Syst Biol 2006, 2: 2006.0034. [http:\/\/dx.doi.org\/10.1038\/msb4100074]","journal-title":"Mol Syst Biol"},{"issue":"9","key":"1018_CR30","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1038\/nbt.1487","volume":"26","author":"T Shlomi","year":"2008","unstructured":"Shlomi T, Cabili MN, Herrg\u00e5rd MJ, Palsson B, Ruppin E: Network-based prediction of human tissue-specific metabolism. Nat Biotechnol 2008,26(9):1003-1010. [http:\/\/dx.doi.org\/10.1038\/nbt.1487] 10.1038\/nbt.1487","journal-title":"Nat Biotechnol"},{"issue":"9","key":"1018_CR31","doi-asserted-by":"publisher","first-page":"6194","DOI":"10.1128\/AEM.00548-06","volume":"72","author":"R Usaite","year":"2006","unstructured":"Usaite R, Patil KR, Grotkjaer T, Nielsen J, Regenberg B: Global transcriptional and physiological responses of Saccharomyces cerevisiae to ammonium, L-alanine, or L-glutamine limitation. Appl Environ Microbiol 2006,72(9):6194-6203. [http:\/\/dx.doi.org\/10.1128\/AEM.00548-06] 10.1128\/AEM.00548-06","journal-title":"Appl Environ Microbiol"},{"key":"1018_CR32","doi-asserted-by":"publisher","first-page":"e1000270","DOI":"10.1371\/journal.pcbi.1000270","volume":"5","author":"PH Bradley","year":"2009","unstructured":"Bradley PH, Brauer MJ, Rabinowitz JD, Troyanskaya OG: Coordinated concentration changes of transcripts and metabolites in Saccharomyces cerevisiae. PLoS Comput Biol 2009, 5: e1000270. [http:\/\/dx.doi.org\/10.1371\/journal.pcbi.1000270] 10.1371\/journal.pcbi.1000270","journal-title":"PLoS Comput Biol"},{"issue":"8","key":"1018_CR33","doi-asserted-by":"publisher","first-page":"2685","DOI":"10.1073\/pnas.0406811102","volume":"102","author":"KR Patil","year":"2005","unstructured":"Patil KR, Nielsen J: Uncovering transcriptional regulation of metabolism by using metabolic network topology. Proc Natl Acad Sci U S A 2005,102(8):2685-2689. [http:\/\/dx.doi.org\/10.1073\/pnas.0406811102] 10.1073\/pnas.0406811102","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1018_CR34","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1038\/msb4100085","volume":"2","author":"T Cakir","year":"2006","unstructured":"Cakir T, Patil KR, iIsen Onsan Z, Ulgen KO, Kirdar B, Nielsen J: Integration of metabolome data with metabolic networks reveals reporter reactions. Mol Syst Biol 2006, 2: 50. [http:\/\/dx.doi.org\/10.1038\/msb4100085]","journal-title":"Mol Syst Biol"},{"key":"1018_CR35","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1093\/bioinformatics\/btq089","volume":"26","author":"D Beisser","year":"2010","unstructured":"Beisser D, Klau GW, Dandekar T, Mueller T, Dittrich M: BioNet: an R-Package for the functional analysis of biological networks. Bioinformatics 2010, 26: 1129-1130. [http:\/\/dx.doi.org\/10.1093\/bioinformatics\/btq089] 10.1093\/bioinformatics\/btq089","journal-title":"Bioinformatics"},{"key":"1018_CR36","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/nar\/28.1.27","volume":"28","author":"M Kanehisa","year":"2000","unstructured":"Kanehisa M, Goto S: KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res 2000, 28: 27-30. 10.1093\/nar\/28.1.27","journal-title":"Nucleic Acids Res"},{"issue":"19","key":"1018_CR37","doi-asserted-by":"publisher","first-page":"10781","DOI":"10.1073\/pnas.181597298","volume":"98","author":"K Fellenberg","year":"2001","unstructured":"Fellenberg K, Hauser NC, Brors B, Neutzner A, Hoheisel JD, Vingron M: Correspondence analysis applied to microarray data. Proc Natl Acad Sci U S A 2001,98(19):10781-10786. [http:\/\/dx.doi.org\/10.1073\/pnas.181597298] 10.1073\/pnas.181597298","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1018_CR38","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1093\/biomet\/41.1-2.133","volume":"41","author":"AR Jonckheere","year":"1954","unstructured":"Jonckheere AR: A distribution-free K-sample test against ordered alternatives. Biometrika 1954, 41: 133-145.","journal-title":"Biometrika"},{"key":"1018_CR39","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/S1385-7258(52)50043-X","volume":"55","author":"TJ Terpstra","year":"1952","unstructured":"Terpstra TJ: The asymptotic normality and consistency of Kendall\u2019s test against trend, when ties are present in one ranking. Proc Kon Ned Akad v Wetensch 1952, 55: 327-333.","journal-title":"Proc Kon Ned Akad v Wetensch"},{"key":"1018_CR40","first-page":"175","volume":"76","author":"H Mack","year":"1981","unstructured":"Mack H, Wolfe D: K-sample rank tests for umbrella alternatives. J Am Stat Ass 1981, 76: 175-181.","journal-title":"J Am Stat Ass"},{"issue":"Web Server issu","key":"1018_CR41","doi-asserted-by":"publisher","first-page":"W182","DOI":"10.1093\/nar\/gkm321","volume":"35","author":"Y Moriya","year":"2007","unstructured":"Moriya Y, Itoh M, Okuda S, Yoshizawa AC, Kanehisa M: KAAS: an automatic genome annotation and pathway reconstruction server. Nucleic Acids Res 2007,35(Web Server issue):W182-W185. [http:\/\/dx.doi.org\/10.1093\/nar\/gkm321]","journal-title":"Nucleic Acids Res"},{"key":"1018_CR42","volume-title":"Biochemical Pathways: An Atlas of Biochemistry and Molecular Biology","author":"G Michal","year":"1998","unstructured":"Michal G: Biochemical Pathways: An Atlas of Biochemistry and Molecular Biology. Wiley-Spektrum; 1998. [http:\/\/www.amazon.com\/exec\/obidos\/redirect?tag=citeulike07-20path=ASIN\/0471331309]"},{"issue":"11","key":"1018_CR43","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1038\/81137","volume":"18","author":"O Fiehn","year":"2000","unstructured":"Fiehn O, Kopka J, D\u00f6rmann P, Altmann T, Trethewey RN, Willmitzer L: Metabolite profiling for plant functional genomics. Nat Biotechnol 2000,18(11):1157-1161. [http:\/\/dx.doi.org\/10.1038\/81137] 10.1038\/81137","journal-title":"Nat Biotechnol"},{"key":"1018_CR44","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1007\/978-1-59745-244-1_2","volume":"358","author":"A Erban","year":"2007","unstructured":"Erban A, Schauer N, Fernie AR, Kopka J: Nonsupervised construction and application of mass spectral and retention time index libraries from time-of-flight gas chromatography-mass spectrometry metabolite profiles. Methods Mol Biol 2007, 358: 19-38. 10.1007\/978-1-59745-244-1_2","journal-title":"Methods Mol Biol"},{"issue":"5","key":"1018_CR45","doi-asserted-by":"publisher","first-page":"732","DOI":"10.1093\/bioinformatics\/btn023","volume":"24","author":"A Luedemann","year":"2008","unstructured":"Luedemann A, Strassburg K, Erban A, Kopka J: TagFinder for the quantitative analysis of gas chromatography\u2013mass spectrometry (GC-MS)-based metabolite profiling experiments. Bioinformatics 2008,24(5):732-737. [http:\/\/dx.doi.org\/10.1093\/bioinformatics\/btn023] 10.1093\/bioinformatics\/btn023","journal-title":"Bioinformatics"},{"issue":"2","key":"1018_CR46","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1007\/s11306-010-0198-7","volume":"6","author":"J Hummel","year":"2010","unstructured":"Hummel J, Strehmel N, Selbig J, Walther D, Kopka J: Decision tree supported substructure prediction of metabolites from GC-MS profiles. Metabolomics 2010,6(2):322-333. [http:\/\/dx.doi.org\/10.1007\/s11306-010-0198-7] 10.1007\/s11306-010-0198-7","journal-title":"Metabolomics"},{"issue":"2","key":"1018_CR47","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1016\/j.jchromb.2008.04.042","volume":"871","author":"N Strehmel","year":"2008","unstructured":"Strehmel N, Hummel J, Erban A, Strassburg K, Kopka J: Retention index thresholds for compound matching in GC-MS metabolite profiling. J Chromatogr B Analyt Technol Biomed Life Sci 2008,871(2):182-190. [http:\/\/dx.doi.org\/10.1016\/j.jchromb.2008.04.042] 10.1016\/j.jchromb.2008.04.042","journal-title":"J Chromatogr B Analyt Technol Biomed Life Sci"},{"key":"1018_CR48","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1186\/1471-2164-10-469","volume":"10","author":"F F\u00f6rster","year":"2009","unstructured":"F\u00f6rster F, Liang C, Shkumatov A, Beisser D, Engelmann JC, Schn\u00f6lzer M, Frohme M, M\u00fcller T, Schill RO, Dandekar T: Tardigrade workbench: comparing stress-related proteins, sequence-similar and functional protein clusters as well as RNA elements in tardigrades. BMC Genomics 2009, 10: 469. [http:\/\/dx.doi.org\/10.1186\/1471-2164-10-469] 10.1186\/1471-2164-10-469","journal-title":"BMC Genomics"},{"issue":"3","key":"1018_CR49","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1101\/gr.8.3.175","volume":"8","author":"B Ewing","year":"1998","unstructured":"Ewing B, Hillier L, Wendl MC, Green P: Base-calling of automated sequencer traces using phred. I. Accuracy assessment. Genome Res 1998,8(3):175-185.","journal-title":"Genome Res"},{"issue":"3","key":"1018_CR50","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1101\/gr.8.3.186","volume":"8","author":"B Ewing","year":"1998","unstructured":"Ewing B, Green P: Base-calling of automated sequencer traces using phred. II. Error probabilities. Genome Res 1998,8(3):186-194.","journal-title":"Genome Res"},{"key":"1018_CR51","unstructured":"Green P: cross_match. [http:\/\/www.phrap.org]"},{"key":"1018_CR52","unstructured":"Dlugosch KM: SnoWhite: A cleaning pipeline for Roche 454 cDNA sequences. [http:\/\/www.kdlugosch.net\/software]"},{"issue":"13","key":"1018_CR53","doi-asserted-by":"publisher","first-page":"1658","DOI":"10.1093\/bioinformatics\/btl158","volume":"22","author":"W Li","year":"2006","unstructured":"Li W, Godzik A: Cd-hit: a fast program for clustering and comparing large sets of protein or nucleotide sequences. Bioinformatics 2006,22(13):1658-1659. [http:\/\/dx.doi.org\/10.1093\/bioinformatics\/btl158] 10.1093\/bioinformatics\/btl158","journal-title":"Bioinformatics"},{"key":"1018_CR54","unstructured":"Broberg P: SAGx: Statistical Analysis of the GeneChip. 1.22.0. 2010. [http:\/\/home.swipnet.se\/pibroberg\/expression_hemsida1.html[Rpackageversion1.22.0] 1.22.0. 2010."},{"issue":"11","key":"1018_CR55","doi-asserted-by":"publisher","first-page":"1470","DOI":"10.1093\/bioinformatics\/btp167","volume":"25","author":"JD Zhang","year":"2009","unstructured":"Zhang JD, Wiemann S: KEGGgraph: a graph approach to KEGG PATHWAY in R and bioconductor. Bioinformatics 2009,25(11):1470-1471. [http:\/\/dx.doi.org\/10.1093\/bioinformatics\/btp167] 10.1093\/bioinformatics\/btp167","journal-title":"Bioinformatics"},{"key":"1018_CR56","first-page":"1695","volume":"Complex Systems","author":"G Csardi","year":"2006","unstructured":"Csardi G, Nepusz T: The igraph software package for complex network research. InterJournal 2006, Complex Systems: 1695. [http:\/\/igraph.sf.net","journal-title":"InterJournal"},{"issue":"2","key":"1018_CR57","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1101\/gr.234503","volume":"13","author":"J F\u00f6rster","year":"2003","unstructured":"F\u00f6rster J, Famili I, Fu P, Palsson B, Nielsen J: Genome-scale reconstruction of the Saccharomyces cerevisiae metabolic network. Genome Res 2003,13(2):244-253. [http:\/\/dx.doi.org\/10.1101\/gr.234503] 10.1101\/gr.234503","journal-title":"Genome Res"},{"issue":"10","key":"1018_CR58","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.1093\/bioinformatics\/btg148","volume":"19","author":"S Pounds","year":"2003","unstructured":"Pounds S, Morris SW: Estimating the occurrence of false positives and false negatives in microarray studies by approximating and partitioning the empirical distribution of p-values. Bioinformatics 2003,19(10):1236-1242. 10.1093\/bioinformatics\/btg148","journal-title":"Bioinformatics"},{"issue":"10","key":"1018_CR59","doi-asserted-by":"publisher","first-page":"R80","DOI":"10.1186\/gb-2004-5-10-r80","volume":"5","author":"RC Gentleman","year":"2004","unstructured":"Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, Dudoit S, Ellis B, Gautier L, Ge Y, Gentry J, Hornik K, Hothorn T, Huber W, Iacus S, Irizarry R, Leisch F, Li C, Maechler M, Rossini AJ, Sawitzki G, Smith C, Smyth G, Tierney L, Yang JYH, Zhang J: Bioconductor: open software development for computational biology and bioinformatics. Genome Biol 2004,5(10):R80. [http:\/\/dx.doi.org\/10.1186\/gb-2004-5-10-r80] 10.1186\/gb-2004-5-10-r80","journal-title":"Genome Biol"},{"key":"1018_CR60","volume-title":"L\u2019Analyse des Donn\u00e9es. L\u2019Analyse des Correspondences., Volume II","author":"JP Benz\u00e9cri","year":"1973","unstructured":"Benz\u00e9cri JP: L\u2019Analyse des Donn\u00e9es. L\u2019Analyse des Correspondences., Volume II. Paris, France: Dunod; 1973."},{"issue":"6","key":"1018_CR61","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1111\/j.1654-1103.2003.tb02228.x","volume":"14","author":"P Dixon","year":"2003","unstructured":"Dixon P, Palmer MW: VEGAN, a package of R functions for community ecology. J Vegetation Sci 2003,14(6):927-930. [http:\/\/dx.doi.org\/10.1658\/1100-9233(2003)014[0927:VAPORF]2.0.CO;2] 10.1111\/j.1654-1103.2003.tb02228.x","journal-title":"J Vegetation Sci"},{"key":"1018_CR62","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/75556","volume":"25","author":"M Ashburner","year":"2000","unstructured":"Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, Harris MA, Hill DP, Issel-Tarver L, Kasarskis A, Lewis S, Matese JC, Richardson JE, Ringwald M, Rubin GM, Sherlock G: Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet 2000, 25: 25-29. [http:\/\/dx.doi.org\/10.1038\/75556] 10.1038\/75556","journal-title":"Nat Genet"},{"issue":"2","key":"1018_CR63","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1093\/bioinformatics\/btl567","volume":"23","author":"S Falcon","year":"2007","unstructured":"Falcon S, Gentleman R: Using GOstats to test gene lists for GO term association. Bioinformatics 2007,23(2):257-258. 10.1093\/bioinformatics\/btl567","journal-title":"Bioinformatics"}],"container-title":["BMC Systems Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1752-0509-6-72.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T17:29:56Z","timestamp":1630517396000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcsystbiol.biomedcentral.com\/articles\/10.1186\/1752-0509-6-72"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,6,19]]},"references-count":63,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2012,12]]}},"alternative-id":["1018"],"URL":"https:\/\/doi.org\/10.1186\/1752-0509-6-72","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.718174271.793486773","asserted-by":"object"}]},"ISSN":["1752-0509"],"issn-type":[{"value":"1752-0509","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,6,19]]},"assertion":[{"value":"3 December 2011","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 May 2012","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 June 2012","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"72"}}